Renal & Urology News December 2014 Issue

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RRT Used Successfully in Ebola Case

© CDC/ FREDERICK A. MURPHY

Emory University physicians describe their experience and offer clinical guidance

THE EBOLA VIRUS IS NOT likely to be found in hemodialysis effluent.

Binder Cuts IV Iron, ESA Use PHILADELPHIA—Ferric citrate is an efficacious and safe phosphate binder that increases iron stores and decreases the use of intravenous (IV) iron and erythropoiesis-stimulating agents (ESAs) over 52 weeks, researchers reported at the 2014 Kidney Week meeting.

The phase 3 open-label trial, led

by Julia B. Lewis, MD, professor of

medicine at Vanderbilt University in Nashville, Tenn., included 168 of 441 end-stage renal disease (ESRD) patients previously enrolled in a pivotal 4-week trial in which they received either ferric citrate or active control. In the new study, which extends observations by another 48 weeks, patients continued on page 5

COVERAGE OF KIDNEY WEEK 2014

American Society of Nephrology’s Kidney Week in Philadelphia Low BP may be beneficial in ADPKD.

PAGES 9 AND 10

BY JODY A. CHARNOW PHILADELPHIA—At the annual Kidney Week meeting here, physicians provided details of the first successful delivery of renal replacement therapy (RRT) to a patient with Ebola virus disease (EVD) and offered advice on how to administer RRT safely in such cases.

The patient acquired EVD while working at an Ebola treatment unit in the West African nation of Sierra Leone and was transported to Emory University in Atlanta. Speaking before meeting attendees, Michael J. Connor, Jr., MD, and Harold A. Franch, MD, both of Emory, described the case and the protocol used for the patient’s care.

Dr. Connor and Dr. Franch, as well as other clinicians, described their experi-

Urolithiasis Raises Risk of Fracture KIDNEY STONE FORMERS may be at elevated risk for fracture, according to a new study.

Using The Health Improvement Network database, Michelle R. Denburg, MD, of the Children’s Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania in Philadelphia, and colleagues studied a retrospective cohort of 51,785 individuals with urolithiasis and 517,267 randomly selected age-, sex-, and practice-matched matched subjects.

Over a median observation period for ascertainment of incident fracture of 4.7 years in both groups, 3,524 incident fractures (118 per 10,000 person-years) occurred in participants with urolithiasis compared with 29,590 in those without urolithiasis (101 per 10,000 person-years), the researchers reported online ahead of print in the Clinical Journal of the American Society of Nephrology. Among subjects with uro-

ence in a paper published online ahead of print in the Journal of the American Society of Nephrology (JASN) to coincide with the Ebola session.

“In our opinion,” Dr. Connor said, “this report confirms that with adequate training, preparation, and adherence to safety protocols, renal replacement therapies can be provided safely and should be considered a viable option to provide advanced supportive care in patients with Ebola.”

Dr. Franch, a nephrologist who oversaw the delivery of RRT to the patient, noted that extra training of volunteer intensive care unit nurses made success possible. “We thank them for their bravery and commitment,” he said. continued on page 5

IN THIS ISSUE 8

Bariatric surgery raises kidney stone rates

9

Niacin administration may slow CKD progression

9

High ferritin increases mortality in hemodialysis patients

10

Earlier ESA use benefits nondialysis CKD patients

13

Exercise could have a protective effect against ESRD

14

Fewer women than men receive hemodialysis

29

Diabetes in RCC patients may increase their death risk

Patient portals can be timesavers for physicians’ offices.

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D E C E M B E R 2 014

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VOLUME 13, ISSUE NUMBER 12

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Laser Prostatectomy Gaining on TURP From 2000 to 2011, use of transurethral resection of the prostate declined and laser procedures increased LASER PROSTATECTOMIES ON THE RISE A study of 90,670 men who underwent surgery for benign prostatic hyperplasia showed that the proportion of patients undergoing laser procedures increased significantly and the proportion of those undergoing transurethral resection of the prostate decrease.

80

TURP

70

Laser surgery

60 50 40 30 20 10 0

2000–2002

2009–2011

Source: Chughtai BI et al. Trends and utilization of laser prostatectomy in ambulatory surgical procedures for the treatment of benign prostatic hyperplasia (BPH) in New York State (2000–2011). J Endourol. 2014; published online ahead of print.

TRANSURETHRAL resection of the prostate (TURP) is still the most common surgical treatment for benign prostatic hyperplasia (BPH), but its rate of use has been declining in the wake of a growing popularity of laser prostatectomies, according to a study.

Using the New York Statewide Planning and Cooperation System database, Bilal I. Chughtai, MD, and colleagues at Weill Medical College of Cornell University in New York, studied 90,670 men who underwent BPHrelated surgery from October 2000 to December 2011. The use of laser prostatectomy (coagulation, enucleation, or vaporization) rose significant from 6.4% of cases in 2000–2002 to 44.5% in 2009–2011, whereas the use

EBRT Outcomes Worse in Smokers Mutations May PROSTATE CANCER (PCa) patients Radiation Oncology at Memorial Predict Bad who smoke while undergoing external Sloan-Kettering Center in New York beam radiation therapy (EBRT) are at analyzed data from 2,156 PCa patients PCa Outcomes significantly increased risk of dying receiving EBRT and who had smok80

TURP

70

Laser surgery

60 50

from their40cancer compared with their never-smoking counterparts, accord30 ing to a new study.

20 Michael J. Zelefsky, MD, and 10 colleagues in the Department of 0

2000-2002

ing histories recorded in their medical charts. The investigators classified patients as never smokers, current smokers, former smokers, and curcontinued on page 5 2009-2011

COVERAGE OF KIDNEY WEEK 2014

American Society of Nephrology’s Kidney Week in Philadelphia Low BP may be beneficial in ADPKD.

PAGES 9 AND 10

FOLLOWING RADICAL treatment for prostate cancer (PCa), men who carry BRCA gene mutations have worse outcomes than non-carriers, according to new findings.

BRCA mutation carriers treated at diagnosis with curative intent by radical prostatectomy (RP) or radiotherapy (RT) are more likely to develop metastasis and to die from PCa, researchers reported.

“Pending future studies confirming the biologic role of BRCA genetic alternations in this setting, our results support closer follow-up of these patients and the need for clinical trials to tailor the best radical/adjuvant treatments,” the authors, led by Elena Castro, MD, of the Spanish National Cancer Research Institute in Madrid, wrote in a paper published online ahead of print in European Urology.

Dr. Castro and her colleagues studied 1,302 men with local or locally advanced PCa, including 67 BRCA

of TURP declined significantly from 72.2% to 48.3% of cases during the same time periods, Dr. Chughtai’s team reported online ahead of print in the Journal of Endourology.

In adjusted analyses, patients aged 45 years or older were progressively less likely to receive laser treatments.

Compared with patients younger than 45, those aged 45–65, 65–75, and older than 75 years were 21%, 30%, and 38% less likely to undergo laser surgery.

Additionally, patients with comorbidities were less likely to receive laser treatment. For example, patients with renal failure, cerebrovascular disease, hypertension, and or were continued on page 5

IN THIS ISSUE 3

ADT for more than 1 year increases fracture risk

8

Bariatric surgery found to raise kidney stone rates

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Niacin may slow progression of chronic kidney disease

15

Discontinuing drugs for mRCC may induce tumor flares

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A statin plus metformin could reduce PCa relapse risk

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Novel gene tool predicts bladder cancer recurrence risk

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Diabetes increases risk of death from RCC

Patient portals can be timesavers for physicians’ offices.

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Brief Summary: Please see Full Prescribing Information for additional information

Labor and Delivery No Velphoro treatment-related effects on labor and delivery were seen in animal studies with doses up to 16 times the maximum recommended clinical dose on a body weight basis. The effects of Velphoro on labor and delivery in humans are not known.

Nursing Mothers Since the absorption of iron from Velphoro is minimal, excretion of Velphoro in breast milk is unlikely.

INDICATIONS AND USAGE Velphoro (sucroferric oxyhydroxide) is a phosphate binder indicated for the control of serum phosphorus levels in patients with chronic kidney disease on dialysis.

DOSAGE AND ADMINISTRATION Velphoro tablets must be chewed and not swallowed whole. To aid with chewing and swallowing, tablets may be crushed.

The recommended starting dose of Velphoro is 3 tablets (1,500 mg) per day, administered as 1 tablet (500 mg) 3 times daily with meals.

Adjust by 1 tablet per day as needed until an acceptable serum phosphorus level (less than or equal to 5.5 mg/dL) is reached, with regular monitoring afterwards. Titrate as often as weekly.

DOSAGE FORMS AND STRENGTHS Velphoro (sucroferric oxyhydroxide) chewable tablet 500 mg.

CONTRAINDICATIONS None.

WARNINGS AND PRECAUTIONS Patients with peritonitis during peritoneal dialysis, significant gastric or hepatic disorders, following major gastrointestinal surgery, or with a history of hemochromatosis or other diseases with iron accumulation have not been included in clinical studies with Velphoro. Monitor effect and iron homeostasis in such patients.

ADVERSE REACTIONS In a parallel design, fixed-dose study of 6 weeks duration, the most common adverse drug reactions to Velphoro chewable tablets in hemodialysis patients included discolored feces (12%) and diarrhea (6%).

To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Medical Care North America at 1-800-323-5188 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS Velphoro can be administered concomitantly with ciprofloxacin, digoxin, enalapril, furosemide, HMG-CoA reductase inhibitors, hydrochlorothiazide, losartan, metformin, metoprolol, nifedipine, omeprazole, quinidine and warfarin.

Take alendronate and doxycycline at least 1 hour before Velphoro.

Velphoro should not be prescribed with oral levothyroxine and oral vitamin D analogs.

USE IN SPECIFIC POPULATIONS Pregnancy Pregnancy Category B: Reproduction studies have been performed in rats and rabbits at doses up to 16 and 4 times, respectively, the human maximum recommended clinical dose on a body weight basis, and have not revealed evidence of impaired fertility or harm to the fetus due to Velphoro. However, Velphoro at a dose up to 16 times the maximum clinical dose was associated with an increase in post-implantation loss in pregnant rats. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

There are no adequate and well-controlled studies in pregnant women.

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Pediatric Use The safety and efficacy of Velphoro have not been established in pediatric patients.

Geriatric Use Of the total number of subjects in two active-controlled clinical studies of Velphoro (N=835), 29.7% (n=248) were 65 and over.

No overall differences in safety or effectiveness were observed between these subjects and younger subjects.

OVERDOSAGE There are no reports of overdosage with Velphoro in patients. Since the absorption of iron from Velphoro is low, the risk of systemic iron toxicity is negligible. Hypophosphatemia should be treated by standard clinical practice.

Velphoro has been studied in doses up to 3,000 mg per day.

HOW SUPPLIED/STORAGE AND HANDLING Velphoro are chewable tablets supplied as brown, circular, bi-planar tablets, embossed with “PA 500” on 1 side. Each tablet of Velphoro contains 500 mg iron as sucroferric oxyhydroxide. Velphoro tablets are packaged as follows: NDC 49230-645-51 Bottle of 90 chewable tablets Storage Store in the original package and keep the bottle tightly closed in order to protect from moisture.

Store at 25°C (77°F) with excursions permitted to 15 to 30°C (59 to 86°F).

PATIENT COUNSELING INFORMATION Dosing Recommendations Inform patients that Velphoro tablets must be chewed and not swallowed whole. To aid with chewing and swallowing, the tablets may be crushed [see Dosage and Administration].

Velphoro should be taken with meals.

Some drugs need to be given at least one hour before Velphoro [see Drug Interactions].

Adverse Reactions Velphoro can cause discolored (black) stool. Discolored (black) stool may mask GI bleeding. Velphoro does not affect guaiac based (Hämocult) or immunological based (iColo Rectal, and Hexagon Opti) fecal occult blood tests.

Distributed by: Fresenius Medical Care North America 920 Winter Street Waltham, MA 02451

US Patent Nos. 6174442 and pending, comparable and/or related patents. © 2014 Fresenius Medical Care North America. All rights reserved.

Renal & Urology News 3

Fracture, Prolonged ADT Linked PROLONGED USE OF androgendeprivation therapy (ADT) is associated with substantial risk of fracture in prostate cancer (PCa) patients, but shortterm use is not, investigators reported.

Writing in Prostate Cancer and Prostatic Disease (2014;17:338-342), Alicia K. Morgans, MD, of Vanderbilt University School of Medicine in Nashville, Tenn., and colleagues concluded that these findings “should be considered when weighing the advantages and disadvantages of ADT in men with prostate cancer.”

Dr. Morgans’ group studied 961 PCa survivors with non-metastatic disease at the time of diagnosis and who completed 15-year follow-up surveys. Of the 961 men, 157 (16.3%) received prolonged ADT (more than 1 year), 120 (12.5%) received short-term ADT (1 year or less), and 684 (71.2%) did not received ADT. The risk of self-reported fracture in the entire cohort was 10%; it was 9.5% in untreated men, 9% in men treated with short-term ADT, and 15% among those who had prolonged ADT. In multivariable analysis, men who received prolonged ADT had a significant 2.5 times higher odds of fracture than men who did not received ADT. Additionally, they had a significant 5.9 times higher odds of undergoing bone mineral testing and 4.3 times higher odds of bone medication use. “To the best of our knowledge,” the researchers wrote, “our analysis is the first to report that the use of bone medications was significantly more common among men treated with prolonged ADT compared with untreated men, possibly indicating the practitioners are increasingly implementing appropriate osteoporosis and fracture prevention strategies, and counseling these high-risk patients.”

Men who received short-term ADT reported rates of fracture similar to men not treated with ADT, according to the investigators.

“Continued efforts to reduce skeletal complications for men receiving ADT should focus on reducing overtreatment of men with ADT when possible, and addressing skeletal health screening and complication prevention in men receiving prolonged ADT,” the authors concluded. n

11/20/14 4:30 PM

4 Renal & Urology News

DECEMBER 2014 www.renalandurologynews.com

FROM THE EDITOR EDITORIAL ADVISORY BOARD

The Renal & Urology News Top 5 Lists for 2014

A

mong the most important challenges in producing a medical newspaper, especially one aimed at a select audience (e.g., nephrologists and urologists), is deciding what studies or topics on which to report from the various conferences we attend and peer-reviewed journals we scan regularly. Renal & Urology News has conducted reader print surveys from time to time to get an idea of what published articles nephrologists and urologists found important or relevant, and to ask what topics they think should receive greater coverage. While these surveys have been helpful, as a practical matter, we can only ask about a very limited number of the hundreds of articles we publish each year.

Our website has changed that. It has given us an expedient way to get feedback on all the articles we publish. We simply tally up the number of clicks each article gets. It is November 20 as I write this, and as the end of 2014 nears, I became curious as to which articles garnered the most reader interest over the previous 11 months. Consequently, I asked my web editor to provide me with the top 5 articles in nephrology and urology (based on the number of clicks they received) thus far in 2014. Here are the headlines of the top 5 articles in each specialty, in descending order of popularity:

Nephrology 1. FDA Clears Lab Test for Predicting Acute Kidney Injury 2. The Challenge of Dialysis at the End of Life 3. Contrast-Induced Nephropathy Risk Minimal 4. Kidney Donors Face Higher ESRD Risk 5. Hemodialysis Fistulas May Cause Adverse Cardiac Effects Urology 1. AUA Kidney Stone Guidelines Unveiled 2. Erectile Dysfunction Drugs Used Improperly 3. Optimal PSA Threshold for Targeted Biopsy Identified 4. Omega-3s and Prostate Cancer: What to Advise Patients 5. Novel Peyronie’s Disease Treatment Shows Efficacy Based on the headlines, do you find these topics compelling? Are we on the right track regarding what we cover? Feel free to send me an e-mail (jody.charnow@haymarketmedia.com) with your thoughts and suggestions.

When you read this, it will likely be mid-December and the holiday season is in full swing. We here at Renal & Urology News would like to wish you all the best.

Jody A. Charnow Editor

Medical Director, Urology

Medical Director, Nephrology

Robert G. Uzzo, MD, FACS G. Willing “Wing” Pepper Chair in Cancer Research Professor and Chairman Department of Surgery Fox Chase Cancer Center Temple University School of Medicine Philadelphia

Kamyar Kalantar-Zadeh, MD, MPH, PhD Medical Director, Nephrology Professor & Chief Division of Nephrology & Hypertension University of California, Irvine School of Medicine Orange, Calif.

Nephrologists

Urologists

Anthony J. Bleyer, MD, MS Professor of Internal Medicine/Nephrology Wake Forest University School of Medicine Winston-Salem, N.C.

Christopher S. Cooper, MD Director, Pediatric Urology Children’s Hospital of Iowa Iowa City

Suphamai Bunnapradist, MD Director of Research Department of Nephrology Kidney Transplant Research Center The David Geffen School of Medicine at UCLA

R. John Honey, MD Head, Division of Urology, Endourology/Kidney Stone Diseases St. Michael’s Hospital University of Toronto Stanton Honig, MD Department of Urology Yale University School of Medicine New Haven, CT J. Stephen Jones, MD, FACS Vice President Regional Medical Operations Professor & Horvitz/Miller Distinguished Chair in Urological Oncology Cleveland Clinic Regional Hospitals Jaime Landman, MD Professor of Urology and Radiology Chairman, Department of Urology University of California Irvine

Csaba P. Kovesdy, MD Chief of Nephrology Memphis VA Medical Center Fred Hatch Professor of Medicine University of Tennessee Health Science Center, Memphis Edgar V. Lerma, MD, FACP, FASN, FAHA Clinical Associate Professor of Medicine Section of Nephrology Department of Medicine University of Illinois at Chicago College of Medicine, Chicago Allen Nissenson, MD Emeritus Professor of Medicine The David Geffen School of Medicine at UCLA, Chief Medical Officer, DaVita Inc.

James M. McKiernan, MD Assistant Professor of Urology Columbia University College of Physicians and Surgeons New York City

Rulan Parekh, MD, MS Associate Professor of Pediatrics and Medicine University of Toronto

Kenneth Pace, MD, MSc, FRCSC Assistant Professor Division of Urology St. Michael’s Hospital University of Toronto

Robert Provenzano, MD Chief, Section of Nephrology St. John Hospital and Medical Center, Detroit Robert S. Rigolosi, MD Director, Regional Hemodialysis Center Holy Name Hospital, Teaneck, N.J.

Ryan F. Paterson, MD, FRCSC Assistant Professor Division of Urologic Sciences University of British Columbia Vancouver, Canada

Lynda Anne Szczech, MD, MSCE Medical Director, Pharmacovigilence and Global Product Development, PPD, Inc. Morrisville, N.C.

Renal & Urology News Staff

Editor Jody A. Charnow Production editor Kim Daigneau Web editor

Stephan Cho

Group art director, Haymarket Medical Jennifer Dvoretz

Production manager Krassi Varbanov

Production director Kathleen Millea Grinder Circulation manager Paul Silver National accounts manager William Canning Publisher Dominic Barone Editorial director

Jeff Forster

Senior VP, medical journals & digital products

Jim Burke, RPh

Senior VP, clinical communications group

John Pal

CEO, Haymarket Media Inc.

Lee Maniscalco

Renal & Urology News (ISSN 1550-9478) Volume 13, Number 12. Published monthly by Haymarket Media, Inc., 114 West 26th Street, 4th Floor, New York, NY 10001. Periodicals postage paid at New York, NY, and an additional mailing office. The subscription rates for one year are, in the U.S., $75.00; in Canada, $85.00; all other foreign countries, $110.00. Single issues, $20.00. www.renalandurologynews.com. Postmaster: Send address changes to Renal & Urology News, c/o DMD Data Inc., 2340 River Road, Des Plaines, IL 60018. Copyright: All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means (electronic, mechanical, photocopying, recording, or otherwise) without the prior written permission of Haymarket Media, Inc. Copyright © 2014.

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RRT in Ebola cases continued from page 1

“Our case also shows that dialysis is not a death sentence for patients suffering from Ebola virus disease and recovery of kidney function is possible.”

According to the JASN report, despite aggressive supportive care with intravenous fluids and experimental antiviral treatments, the patient developed hypoxic acute respiratory failure and acute kidney injury (AKI) secondary to acute tubular necrosis on day 8 of illness.

On day 11, continuous RRT (CRRT) via a non-tunneled temporary right internal jugular dialysis catheter was initiated.

As the patient’s overall clinical condition improved, he was transitioned to prolonged intermittent RRT performed for 6–12 hours daily using the CRRT device.

Renal function recovered, allowing for RRT discontinuation after 24 days, with a steadily improving estimated glomerular filtration rate to 33 mL/min/1.73 m2 7 days after RRT discontinuation.

Dr. Connor told listeners that he and his colleagues recommend CRRT for initial treatment because it minimizes exposure of additional staff and equipment to the isolation environment.

The right internal jugular vein is the preferred access site based on KDIGO recommendations, as it tends to have

Binder cuts IV iron use continued from page 1

received ferric citrate that, as before, was supplied as 1 gram tablets containing 210 mg of iron.

Mean phosphorus levels declined from 5.7 mg/dL at baseline to 5.2 mg/dL at week 48, according to the investigators.

From baseline to week 48, transferrin saturation increased from 32.4% to 40.3% and serum ferritin increased from 710 to 821 ng/mL. From week 12 to week 48, IV iron use decreased from 1.48 to 0.72 mg per day, ESA use declined from 893 to 699 units per day, and hemoglobin levels remained stable at 11.3 g/dL. “Ferric citrate is a unique compound because it works in both the bone and mineral domain as well as in the anemia domain,” Dr. Lewis told Renal & Urology News.

Ferric citrate is marketed by Keryx Biopharmaceuticals under the recently FDA-approved trade name Auryxia.

Unlike IV iron, she explained, the absorption of oral ferric citrate is regulated tightly by the gastrointestinal (GI) tract. During the study, 60% of patients on ferric citrate did not require even a single dose of IV iron, and in the last 12

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superior performance and the internal jugular sites typically have the lowest bleeding risk.

CRRT effluent presents a very low infection risk, Dr. Connor said, but, given that it is handled in an Ebolapositive environment, it was treated at Emory as hazardous and disposed of in a similar manner.

Another speaker, Sarah Faubel, MD, professor of medicine at the University of Colorado Denver and chair of the American Society of Nephrology’s AKI Advisory Group, summarized recommendations for developing an EVD protocol, emphasizing that the best protocol incorporates center-specific expertise.

“The right protocol at one center is not going to be the same as the right protocol at another center,” Dr. Faubel stressed.

“Trust what your understanding [is] about how this disease is transmitted, trust your expertise about providing renal replacement therapy, and come up with the best plan at your institution.”

Among other measures, hospitals need to have a biocontainment unit and protocols for protecting healthcare workers, deciding who is going to care for EVD patients, and disposing of waste materials. She emphasized that nephrologists must be involved early in the development of an RRT protocol for Ebola cases. n

weeks of the trial, 85% of ferric citrate recipients were not receiving IV iron.

Importantly, she added, ferric citrate was associated with an excellent safety profile. Those receiving the drug had a lower incidence of serious adverse events, specifically infection-, cardiovascular-, and GI-related SAEs. Dr. Lewis also pointed out that use of ferric citrate was associated with substantial financial benefits. The average cost saving per dialysis patient as a result of reduced IV iron and ESA use was $2,104.

A separate study presented at the meeting demonstrated that phosphorus binding with ferric citrate was associated with lower rates of hospitalization and costs compared with those on sevelamer carbonate or calcium acetate.

A team led by Roger A. Rodby, MD, of Rush University Medical Center in Chicago, found that ferric citrate treatment provided levels of phosphorus control similar to that of active controls, but was associated with a savings of $896 per-patient-per-year (PPPY) for infection-related adverse events, $1,021 PPPY for GI-related adverse events, and $1,033 PPPY for cardiac-related adverse events, with lower overall rates of hospitalization in all 3 categories. n

Renal & Urology News 5

Developing an Ebola Protocol Sarah Faubel, MD, professor of medicine at the University of Colorado Denver, and chair of the American Society of Nephrology’s Acute Kidney Injury Advisory Group, summarized 5 main considerations for developing a renal replacement therapy protocol for handling Ebola cases.

• Dialysis Modality—The best modality probably is continuous renal replacement therapy (CRRT), and hospitals should have a CRRT machine dedicated to the care of Ebola patients.

• Line Placement— The optimal place for line placement is probably the right internal jugular vein, Dr. Faubel said. Placement of a line in that vein must be checked with an x-ray, so if no dedicated x-ray machine is available, the right internal jugular vein may not be a good choice, and a femoral approach may be a better option, she said.

• Dialysis Effluent— Effluent is highly unlikely to contain Ebola virus, she said.

Although the Centers for Disease Control and Prevention said effluent does not need to be disinfected, hospitals should check with the local wastewater department and public health officials.

• Anticoagulation— Clinicians should use the anticoagulation approach with which they are comfortable at their facility, but modifications may need to be made based on the laboratory tests that are available.

• Laboratory tests—Ebola patients will require point-of-care testing, so not all laboratory tests will be available, especially phosphorus testing. “You’re also going to have to think about how frequently you check those labs,” Dr. Faubel said. “In CRRT, we usually check a lot of labs, but you don’t want your healthcare workers to be doing too many blood draws because that’s blood exposure. So you’re probably going to reduce the number of lab checks, and you may have to do empiric electrolyte replacement.” n

Urolithiasis risk continued from page 1

lithiasis, the median time from diagnosis to fracture was 10 years.

Among male participants, urolithiasis was associated with a significant 13% overall increased risk of fracture.

The risk of fracture associated with urolithiasis was significantly elevated among those aged 10–19 years (55% higher), 40–49 years (17% higher), 50–59 years (20% higher), and 80–89 years (25% higher), according to the investigators.

Among female participants, the fracture risk associated with urolithiasis was significantly elevated among those aged 30–39 years (55% higher), 40–49 years (45% higher), 50–59 years (32% higher), 60–69 years (25% higher), and 70–79 years (21% higher).

“Given that the time from initial diagnosis of urolithiasis to first fracture was a decade and that the excess risk affected all skeletal sites, there is reason to believe that we might possibly be able to intervene during this critical interval and decrease the risk of future fracture,” Dr. Denburg’s group concluded.

The researchers stated that their study cannot establish a causal mechanism, but it confirms the association between urolithiasis and risk of subsequent fracture. A previous retrospective study of 624 patients with symptomatic urolithiasis published in Kidney International (1998;53:459-464) of 624 demonstrated a 4-fold increased risk of a first vertebral fracture than expected in the general population.

A subsequent cross-sectional study of 793 participants in the Third National Health and Nutrition Examination Survey showed that men, but not women, who reported a history of renal calculi were more likely to report a history of spine and wrist fractures, according to findings published in the Journal of Bone and Mineral Research (2001;16:1893-1898).

Dr. Denburg and her collaborators noted that current evidence points to an association between idiopathic hypercalciuria (IH) and diminished bone mineral density (BMD). Previous studies have shown that IH in childhood is associated with low BMD, “suggesting that life-long hypercalciuria may compromise bone health and increase fracture risk.” n

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Laser prostectomy continued from page 1

43%, 40%, 17%, and 16% less likely to receive laser treatment compared with patients who did not have these conditions. The researchers called this an interesting observation “since laser therapy is minimally invasive and there is evidence that it is safe and effective

Beginning at age 45, men were increasingly less likely to undergo laser surgery. in patients who are at high risk for surgical complications such as elderly and in those who require anticoagulation therapy.”

One possible explanation, the investigators noted, is that some surgeons are still concerned about safety and prefer to use laser treatments in younger and healthier patients.

“Perhaps if we evaluate a more contemporary cohort where surgeons have gained more expertise and experience with laser technology, we will see more

older patients with comorbid conditions who have been treated with laser therapy.”

The study also showed that Medicaid patients were 42% like likely to undergo laser surgery than those with private insurance. Mid- and high-volume centers (treating an annual average of 100–200 cases and more than 200 cases, respectively) were twofold and fourfold more likely than low-volume centers (treating an annual average of fewer than 100 cases) to use laser procedures. In a propensity-matched cohort, TURP and laser patients had similar complication rates, but the TURP group had a significantly higher proportion of patients with electrolyte disorders than the laser group (2.9% vs. 2.3%).

“Laser surgery and other new technologies continue to change the landscape of BPH-related procedures,” the authors wrote. “As TURP has been the gold standard for surgical treatment of BPH, there is need to understand if new technologies such as laser prostatectomy can be as safe as TURP. Our study provides supportive evidence that laser and TURP have similar in-hospital morbidity as well as low occurrence of complications.” n

Mutation predictions continued from page 1

mutation carriers. Of these patients, 535 underwent RP, including 35 BRCA mutation carriers, and 767 received RT, including 32 BRCA mutation carriers. Subjects had a median follow-up was 64 months.

At 3, 5, and 10 years after treatment, 90%, 72%, and 50% of carriers, respectively, were free from metastasis compared with 97%, 94%, and 84% of noncarriers. The 3-, 5-, and 10-year cancer-specific survival rates were significantly worse in the carrier than noncarrier cohort (96%, 76%, and 61% vs.

99%, 97%, and 85%, respectively).

continued from page 1

rent smoking unknown. The median follow-up was 95 months.

Compared with never smoking, current smoking was associated with a significant 40% increased risk of PSA relapse, 2.4 times increased risk of developing distant metastases, and a 2.2 times increased risk of PCaspecific death, Dr. Zelefsky’s group reported online ahead of print in BJU International. In addition, current and former smokers had a significant 80% and 45% increased risk of EBRT-related genitourinary toxicities, respectively.

“Given the increased risk of prostate cancer progression and radiation toxicity among smokers, a stronger emphasis on smoking cessation is clearly appropriate,” the authors wrote. “With a growing number of cancer survivors nationwide, there is a concomitant increase in attention to behavior medication among survivors.”

Dr. Zelefsky’s team cited research findings showing that upwards of 50% of smokers with cancer continue to smoke after their diagnosis, and PSA relapse rates are higher among those who do not quit. They also noted that

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among those who continue to smoke during radiotherapy the urinary side effects can be accentuated.

Previous studies have found an association between long-term smoking and systemic hypoxia, and hypoxia at the radiotherapy target site is known to decrease treatment efficacy.

Although this association has been better studied in head and neck cancers, Dr. Zelefsky and his colleagues noted, the principle has been shown to apply to PCa as well and could explain the worse prognosis observed among smokers.

For the study, Dr. Zelefsky’s team defined current smokers as those who were smoking at the time of the initial consultation and the initiation of EBRT. They defined former smokers as men who had quit smoking before starting EBRT, even if this cessation occurred several weeks or years before treatment.

The authors acknowledged some study limitations. Smoking histories were self-reported and thus subject to under-reporting. Smoking status was not updated consistently during the years of follow-up, and this could have significantly impacted the effect of smoking on PCa progression and long-term toxicity. n

In multivariate analysis, BRCA mutations independently predicted a nearly 2.4 times increased risk of developing metastatic disease and 2.2 times increased risk of PCa-related death, Dr. Castro and her colleagues reported.

“Despite our results,” they wrote, “the screening of unselected patients for germline BRCA mutations is not justified due to the current cost of the procedure and the low frequency of those events in sporadic PCa.” They pointed out, however, that as technologies evolve and the cost of sequencing genomes and specific gene panels continues to decrease, screening for BRCA mutations may prove cost-effective. n See accompanying commentary below.

C O M M E N TA R Y

Prostate Cancer Genetics: Ready for Clinical Use?

BY SERGE GINZBURG, MD FOR DECADES prostate cancer

with worse metastasis-free cancer-

risk (PCa) stratification was based

specific survival.

primarily on the architectural pattern of the tumor under low magnification

EBRT outcomes

Renal & Urology News 5

These studies contribute to the growing body of literature that recog-

(Gleason score), PSA and DRE. As the

nizes the prognostic value of BRCA.

biological basis of cancers becomes

Although the overall prevalence of

elucidated, our ability to associate

these autosomal dominant mutations

aberrant genes with PCa development

is low and the penetrance variable,

is outpacing our understanding of how

families are becoming more informed

to apply this information clinically.

about their genetic signature. Targeted

PCa detection in men with BRCA1

screening is on the horizon and will

and BRCA2 mutations was compared

ultimately have a favorable impact on

to controls (BRCA1 or BRCA2 nega-

identifying high-risk populations. At

tive, but with family history of these

present, however, the clinical utility of

mutations) in a recent analysis of the

this information remains limited. Until

IMPACT trial. Using a PSA threshold

this knowledge gap is closed, electing

of 3.0 ng/mL the study noted that

preemptive treatments based on one’s

66% of the detected tumors were

genetics may be premature.3 n

1

classified as intermediate or high risk.

Moreover, the 48% positive predic-

Serge Ginzburg, MD, is a urologic

tive value (PPV) for biopsy in BRCA2

oncologist at Albert Einstein Medical

mutation carriers was double the

Center in Elkins Park, Pa., and an

PPV previously reported in other

assistant professor at Fox Chase

population screening studies. In the

Cancer Center in Philadelphia.

current study, Castro et al further

REFERENCES

these observations by comparing the response to the conventional treatment in men with BRCA1 and BRCA2 mutations to those without, deriving the cohorts from EMBRACE and UKPGCS observational studies.2 The authors demonstrate BRCA positivity to independently correlate

1. Bancroft EK, Page EC, Castro E, et al. Targeted prostate cancer screening in BRCA1 and BRCA2 mutation carriers: Results from the initial screening round of the IMPACT Study.

Eur Urol. 2014;66:489-499.

2. Castro E, Goh C, Leongamornlert D, et al.

Effect of BRCA mutations on metastatic relapse and cause-specific survival after radical treatment for localised prostate cancer. Eur Urol.

2014 (published online ahead of print).

3. Uzzo RG. Genetic Risk and PCa Treatment. Renal & Urology News. 2013 (12:6). http://www. renalandurologynews.com/genetic-risk-and-pcatreatment-a-new-era-dawning/article/309627/

11/20/14 7:35 PM

6 Renal & Urology News

DECEMBER 2014

www.renalandurologynews.com

Contents

DECEMBER 2014

■

VOLUME 13, ISSUE NUMBER 12

Nephrology 9

ONLINE

this month at renalandurologynews.com

10

Videos

Low BP May Be Beneficial in ADPKD Researchers observe a slower rate of increase in total kidney volume and reduced left ventricular index.

Data Challenge IV Iron Withholding IV iron in anemic hemodialysis patients hospitalized for bacterial infections does not worsen outcomes.

13

Exercise Decreases Odds of ESRD Strenuous aerobic activities lowered the risk by 42% compared with no physical activity.

15

Renal Hyperfiltration May Predict Higher Mortality It is associated with a 37% increased risk of all-cause mortality and a 66% increased risk of cardiovascular mortality.

Clinical Quiz

Take our latest quiz at renalandurologynews.com /clinical-quiz/. Answer correctly and you will be entered to win a $50 American Express gift card.

Congratulations to our October winner: Susan Marshall, MD

CALENDAR

Urology 3

Fracture Risk Higher With Prolonged ADT The risk was 15% for men on ADT for more than 1 year versus 9% among those on ADT for 1 year or less.

Drug Showcase

15

Halting mRCC Drugs Induces Tumor Flare Researchers observe this response among patients taken off sunitinib or pazopanib.

27

Conscious Sedation Safe for Renal Cryoablation It is associated with shorter procedure times and hospital stays compared with general anesthesia.

News Coverage

Visit our website for timely reports from upcoming meetings.

29

Study: Diabetes Raises RCC Death Risk Diabetes is associated with decreased overall and cancer-specific survival in patients who undergo surgery for clear-cell renal cell carcinoma.

“The finding that the general survival

advantage for women is virtually lost for all adult age groups of individuals on dialysis is striking.

See our story on page 14

006_Neph_RUN1214.indd 6

Genitourinary Cancers Symposium Orlando, Fla. February 26 –28 European Association of Urology 30th Annual Congress Madrid March 20 –24 National Kidney Foundation 2015 Spring Clinical Meetings Dallas March 25 –29 American Transplant Congress Philadelphia May 2– 6 American Urological Association Annual Meeting New Orleans May 15 –19 American Society of Hypertension Annual Scientific Meeting New York May 16 –19

Some of our recent postings include: • Five Considerations for Ebola Care in Dialysis • The Growing Testosterone Debate • Alternative Doses for Renal Cell Carcinoma Agents

Read up on recently-approved pharmaceuticals. Our latest include: • Adempas (riociguat), for chronic hypertension • Farxiga (dapagliflozin), for type 2 diabetes • Fortesta (testosterone gel), for hypogonadism

Annual Dialysis Conference New Orleans January 31– February 3

21

Departments 4

From the Editor The top 5 articles for 2014.

8

News in Brief Vitamin D may protect against bladder cancer.

21

Men’s Health Update CP/CPPS risk lower in physically active men.

26

Practice Management Patient portals can be timesavers for physician offices.

11/20/14 4:19 PM

6 Renal & Urology News

DECEMBER 2014

www.renalandurologynews.com

Contents

DECEMBER 2014

■

VOLUME 13, ISSUE NUMBER 12

Urology 3

ONLINE

this month at renalandurologynews.com

15

27

Clinical Quiz

Take our latest quiz at renalandurologynews.com /clinical-quiz/. Answer correctly and you will be entered to win a $50 American Express gift card.

Congratulations to our October winner: Susan Marshall, MD

Videos

29

CALENDAR

Fracture Risk Higher With Prolonged ADT The risk was 15% for men on ADT for more than 1 year versus 9% among those on ADT for 1 year or less.

Halting mRCC Drugs Induces Tumor Flare Researchers observe this response among patients taken off sunitinib or pazopanib.

Conscious Sedation Safe for Renal Cryoablation It is associated with shorter procedure times and hospital stays compared with general anesthesia.

Study: Diabetes Raises RCC Death Risk Diabetes is associated with decreased overall and cancer-specific survival in patients who undergo surgery for clear-cell renal cell carcinoma.

Nephrology

Drug Showcase

10

Data Challenge IV Iron Withholding IV iron in anemic hemodialysis patients hospitalized for bacterial infections does not worsen outcomes.

13

Exercise Decreases Odds of ESRD Strenuous aerobic activities lowered the risk by 42% compared with no physical activity.

15

Renal Hyperfiltration May Predict Higher Mortality It is associated with a 37% increased risk of all-cause mortality and a 66% increased risk of cardiovascular mortality.

Read up on recently-approved pharmaceuticals. Our latest include: • Adempas (riociguat), for chronic hypertension • Farxiga (dapagliflozin), for type 2 diabetes • Fortesta (testosterone gel), for hypogonadism

News Coverage

Visit our website for timely reports from upcoming meetings.

European Association of Urology 30th Annual Congress Madrid March 20 –24 National Kidney Foundation 2015 Spring Clinical Meetings Dallas March 25 –29 American Transplant Congress Philadelphia May 2– 6 American Urological Association Annual Meeting New Orleans May 15 –19

Low BP May Be Beneficial in ADPKD Researchers observe a slower rate of increase in total kidney volume and reduced left ventricular index.

“The finding that the general survival

advantage for women is virtually lost for all adult age groups of individuals on dialysis is striking.

See our story on page 14

006_Uro_RUN1214.indd 6

Genitourinary Cancers Symposium Orlando, Fla. February 26 –28

American Society of Hypertension Annual Scientific Meeting New York May 16 –19

Some of our recent postings include: • Five Considerations for Ebola Care in Dialysis • The Growing Testosterone Debate • Alternative Doses for Renal Cell Carcinoma Agents

9

Annual Dialysis Conference New Orleans January 31– February 3

21

Departments 4

From the Editor The top 5 articles for 2014.

8

News in Brief Vitamin D may protect against bladder cancer.

21

Men’s Health Update CP/CPPS risk lower in physically active men.

26

Practice Management Patient portals can be timesavers for physician offices.

11/20/14 4:17 PM

8 Renal & Urology News

DECEMBER 2014

www.renalandurologynews.com

News in Brief

Please visit us at www.renalandurologynews.com for the latest news updates from the fields of urology and nephrology

Short Takes Vitamin D May Protect Against Bladder Cancer

horts had a mean preoperative body mass index was 46.7 kg/m2.

Kidney stone rates were similar at

High serum levels of vitamin D may have a protective effect against blad-

baseline for the 2 groups, but during 6

der cancer, according to a recent

years of follow-up, new stone formation

systematic review and meta-analysis

increased significantly in the surgery

published online ahead of print in

patients (11%) versus controls (4.3%),

Tumor Biology.

according to findings published online ahead of print in Kidney International.

The meta-analysis, by Yong Liao, MD, and colleagues at Sichuan Academy of People’s Hospital in Chengdu, China, in-

Aspirin Cuts PCSM in High-Risk Cases

cluded 89,610 participants and 2,238

Men with high-risk prostate cancer

bladder cancer cases. A high serum

(PCa) who take aspirin daily after be-

level of 25-hydroxyvitamin D was asso-

ing diagnosed with the disease have a

ciated with a significant 25% decreased

decreased risk of PCa-specific mortal-

relative risk of bladder cancer.

ity (PCSM), researchers reported

Medical Sciences & Sichuan Provincial

online ahead of print in the Journal of

Bariatric Surgery Ups Kidney Stone Rates

Clinical Oncology.

Bariatric surgery is associated with an

can Cancer Society in Atlanta, and

increased rate of kidney stones.

colleagues analyzed data from 7,118

Eric J. Jacobs, PhD, of the Ameri-

patients with non-metastatic PCa who

John C. Lieske, MD, and colleagues at Mayo Clinic in Rochester, Minn.,

had information on post-diagnosis as-

studied 762 Olmsted County,

pirin use. Of these, 301 died. Among

Minnesota, residents who underwent

men with high-risk PCa—defined as

bariatric surgery. Of these, 78% had

stage T3 or higher and/or Gleason

standard Roux-en-Y gastric bypass.

score of 8 or higher—post-diagnosis

The surgery patients were matched

aspirin use was associated with a sig-

with equally obese control individuals

nificant 40% decreased risk of PCSM

who did not undergo surgery. Both co-

compared with non-use.

Congress and the Affordable Care Act In a recent online poll, Renal & Urology News asked readers, “What should the Republican-controlled Congress do about the Affordable Care Act?” Here are the results based on 226 responses.

Leave it alone: 36.28% Attempt to repeal it: 23.89% Change certain key provisions: 36.73% Do not know: 3.1%

0

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15

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High-Dose Statins May Cut Contrast-Induced AKI Risk H

igh-dose statins may prevent contrast-induced acute kidney injury (AKI) in patients undergoing coronary angiography, according to the findings of a recent meta-analysis published in The American Journal of Cardiology (2014;114:1295-1302).

The meta-analysis, by Anene Ukaigwe, MD, and colleagues at Reading Health System in West Reading, Pa., included 12 randomized controlled trials with a total of 5,564 patients. Contrast-induced AKI occurred in 94 of 2,769 patients (3.4%) pretreated with high-dose statins and 213 of 2,795 patients (7.6%) pretreated with low-dose statins or placebo, a difference that translated into a significant 57% decreased odds of contrast-induced AKI. The benefit of high-dose statins also was observed in subgroup analyses. In patients with diabetes or documented renal insufficiency, high-dose statin use was associated with significant 40% and 34% decreased odds of contrast-induced AKI.

Hyponatremia at Admission Increases Mortality Risk H

yponatremia at the time of hospital admission is associated with an increased risk of death and longer in-patient stays, according to a new study.

Louise Balling, MD, of the Department of Cardiology, Rigshospitalet, University of Copenhagen, Denmark, and colleagues studied 2,960 patients older than 40 years who were admitted to a hospital in Greater Copenhagen. Hyponatremia, defined as a plasma sodium level below 137 mmol/L at hospital admission, was present in 1,105 patients (37.3%). Patients had a median follow-up period of 5.16 years.

The 1-year mortality rate was higher for patients with hyponatremia than in those with normonatremia (27.55 vs. 17.7%), the researchers reported online ahead of print in the Internal Medicine Journal. Hyponatremia independently predicted a significant 60% and 40% increased risk of short- and long-term all-cause mortality after 1 year and after the entire observation period, respectively, according to the investigators. Patients with hyponatremia had a hospital stay of 7.6 days compared with 5.6 days for those with normonatremia, a significant difference between the groups.

LOS Predictors for Infants Hospitalized with UTI Y

ounger age and preterm birth are among the clinical factors that predict a longer length of stay (LOS) for infants hospitalized with a urinary tract infection (UTI), according to Canadian researchers.

Researchers led by Patricia C. Parkin, MD, of The Hospital for Sick Children in Toronto, conducted a case-control study of 142 infants younger than 6 months hospitalized with UTI. They defined cases as infants who had a LOS of 96 hours or more and controls as those who had a LOS less than 96 hours. Each group had 71 patients.

Compared with controls, cases were significantly more likely to be younger (4.2 vs. 7.1 weeks) and to be born premature (13% vs. 3%), Dr. Parkin’s group reported in Hospital Pediatrics (2014;4:291-297). They also had a significantly longer duration of intravenous antibiotics (125 vs. 62 hours).

11/20/14 4:37 PM

www.renalandurologynews.com DECEMBER 2014

■ Kidney Week 2014

Renal & Urology News 9

Reports below are from the American Society of Nephrology’s Kidney Week 2014 in Philadelphia

Low BP May Be Beneficial in ADPKD RIGOROUS BLOOD pressure control can reduce the rate of increase in total kidney volume (TKV) in young hypertensive patients with autosomal dominant polycystic kidney disease (ADPKD) and relatively preserved kidney function, a researcher reported.

“Low blood pressure treatment in healthy young hypertensive ADPKD patients with renin-angiotensin-system blockade is well tolerated and safe and results in a 14.2% slower rate of total kidney volume growth over 5 years, [and] is associated with reduced left ventricular mass index, urinary albumin excretion, and renal vascular resistance,” Arlene B. Chapman, MD, of Emory University in Atlanta, said during a press conference.

Dr. Chapman presented the findings of a placebo-controlled, double-blind study of 558 hypertensive ADPKD patients aged 15–49 years who had an estimated glomerular filtration rate (eGFR) above 60 mL/min/1.73 m2. She and her colleagues compared the effect of low ver-

Kidney Stones May Increase RCC Risk PATIENTS WITH A history of kidney stones are at significantly higher risk of renal cell carcinoma (RCC) and transitional cell carcinoma (TCC), according to a meta-analysis.

The meta-analysis, by Wisit Cheungpasitporn, MD, of Mayo Clinic in Rochester, Minn., and colleagues, included 7 studies. A history of

sus standard blood pressure (BP) and the effect of the ACE inhibitor lisinopril alone or in combination with the angiotensin receptor blocker (ARB) telmisartan on the annual percent change in TKV. The researchers defined low BP as 95–110/60–75 mm Hg and standard BP as 120–130/70–80 mm Hg. The annual increase in TKV was 5.6% in the low BP group compared with 6.6% in the standard BP group, a significant difference between the groups.

TKV increased by 38% from baseline in the low BP group compared with 44.2% from baseline in the standard BP group at 60 months. Adding telmisartan to lisinopril did not significantly change the rate of increase in TKV. Left ventricular mass index (LVMI) and urinary albumin excretion (UAE) decreased by 1.17 g/m 2 per year and 3.77%, per year, respectively, in the low BP group. In the standard BP group, LVMI decreased by 0.57 g/m2 per year and UAE increased by 2.43%

Maintaining a BP of 95–110/60–75 mm Hg may improve outcomes in patients with autosomal dominant polycystic kidney disease.

per year. The investigators observed a short-term significant decline in eGFR in the low BP group, but not in the standard BP group. In addition, the results demonstrated a marginal but not significant improvement in the

long-term decline in eGFR in the low versus standard BP group.

In a companion double-blind, placebocontrolled trial, the results of which also were presented at the meeting, Vicente E. Torres, MD, PhD, of Mayo Clinic in Rochester, Minn., and collaborators studied of 486 ADPKD patients aged 18–64 years with stage 3 chronic kidney disease and 5–8 years of follow-up.

Patients were randomized to receive lisinopril and placebo or lisinopril and telmisartan titrated to achieve a BP of 110–130/70–80 mm Hg. Treatment with lisinopril alone or in combination with telmisartan lowered urinary aldosterone excretion and adequately controlled BP. The researchers observed no significant difference in the composite primary outcome (time to death, end-stage renal disease, or a 50% reduction from the baseline eGFR) and rate of eGFR decline.

The presentation of the studies coincided with their online publication in The New England Journal of Medicine. n

© THINKSTOCK

Slower rate of increase in total kidney volume and reduced left ventricular index observed

Niacin May Slow CKD Progression NIACIN ADMINISTRATION may slow progression of chronic kidney disease (CKD), researchers reported.

A team led by Csaba P. Kovesdy, MD, of the Memphis Veterans Affairs Medical Center and the University of Tennessee Health Science Center in Memphis, found that niacin treatment was associated with a significant decrease in the proportion of patients with rapid decline in estimated glomerular filtration rate (eGFR) and a significant decrease in all-cause mortality, after adjusting for baseline

demographic and comorbidity factors.

Dysfunctional high-density lipoprotein (HDL), increased reactive oxygen species, inflammation, endothelial dysfunction, hypertriglyceridemia, and hyperphosphatemia have been associated with rapid eGFR decline and increased adverse events, the researchers noted.

Niacin has been shown to improve HDL function, enhancing its antioxidant and anti-inflammatory properties, the researchers pointed out. It also improves endothelial function and decreases triglyceride levels and serum phosphorus.

The cohort had normal baseline eGFR in 2005–2006. Of the 3,353,461 veterans in the cohort, 119,891 were prescribed niacin during 2005–2006.

The researchers examined baseline use of niacin with slopes of eGFR over a median follow-up of 7.7 years. In the total cohort, 9.3% of patients had rapid decline in kidney function (eGFR decline less than −5 mL/min/1.73 m2 per year). In a fully adjusted model, the niacin group had a significant 10% decreased odds of an eGFR slope less than −5 mL/min/1.73 m2 per year. n

kidney stones was associated with a significant 76% increased risk of RCC and a 2.1 times increased risk of TCC, according to the researchers.

In subgroup analyses, the risk of RCC associated with stones was significant only in male subjects. The researchers concluded that their findings may impact clinical management and cancer surveillance. n

News-KW_009_RUN1214.indd 9

Higher Ferritin Ups Mortality in HD Patients HIGHER SERUM ferritin levels are associated with all-cause, cardiovascular, and infection-related mortality among patients on hemodialysis (HD), a Japanese study found.

Yukio Maruyama, MD, of the Jikei University School of Medicine in Tokyo, and colleagues analyzed base-

line data from 162,818 receiving thriceweekly HD. Patients had a median age of 65 years and a median HD vintage of 61 months. During a 1-year followup, 12,800 patients (7.9%) died of all causes. The group included 5,216 (3.2%) who died from cardiovascular causes and 2,230 (1.4%) who died

from infection-related causes.

In multivariable analysis, patients in the highest quartile of serum ferritin had 24%, 10%, and 24% increased odds of all-cause, cardiovascular, and infection-related mortality, respectively, compared with those in the lowest quartile. n

11/20/14 4:50 PM

10 Renal & Urology News

■ Kidney Week 2014

DECEMBER 2014 www.renalandurologynews.com

Reports below are from the American Society of Nephrology’s Kidney Week 2014 in Philadelphia

Earlier ESA Use Benefits CKD Patients STARTING erythropoiesis-stimulating agents (ESAs) when hemoglobin levels fall below 11 rather than 9 or 10 g/dL decreases the risk of renal events in patients with chronic kidney disease (CKD) not on dialysis, according to the findings of a Japanese study.

The study investigators, led by Tadao Akizawa, MD, of Showa University School of Medicine, noted in a poster presentation that early detection and management of anemia is considered vital, but the optimal timing of initiating ESA therapy is unknown. In a prospective observational study, the researchers analyzed data from 1,113 non-dialysis CKD patients not previously treated with ESAs. The study population was 65.3% male and had a mean age of 70.5 years. The most common cause of CKD was diabetic nephropathy (34.9% of cases), followed by nephrosclerosis (24.1%) and chronic glomerulonephritis (22.4%).

The researchers placed patients into 3 groups based on hemoglobin (Hb) level: at least 10 but less than 11 g/dL (group 1); at least 9 but less than 10 g/dL (group 2); and less than 9 g/dL (group 3). The primary study endpoint was the time to the first occurrence of any renal event (initiation of renal replacement therapy, doubling of serum creatinine, or an estimated glomerular filtration rate below 6 mL/min/1.73 m2. ESA treatment consisted of epoetin beta.

The follow-up period was 24 months.

Patients in group 3 had a significant 2.5 times increased risk of renal events compared with those in group 1. The risk of renal events did not differ significantly between patients in groups 1 and 2.

The study also found that lower Hb levels, higher serum creatinine levels, lower serum albumin levels, diabetes mellitus, and previous use of diuretics were associated with significantly decreased odds of renal survival. n

KW_010_RUN1214.indd 10

Living Kidney Donors Are At Higher Risk of Pregnancy Complications LIVING KIDNEY donors are at higher risk of gestational hypertension or preeclampsia than healthy non-donors in the general population, according to a new study conducted in Ontario, Canada.

Most women, however, have uncomplicated pregnancies after kidney donation, said lead investigator Amit X. Garg, MD, PhD, of the London Health Sciences Centre in London, Ontario, who presented study findings at the meeting. Their rates of preterm birth and low birth weight do not differ significantly from healthy non-donors.

Presentation of the study findings coincided with their publication online in The New England Journal of Medicine (NEJM).

Dr. Garg and his colleagues conducted a retrospective cohort study that included 85 female living kidney donors who were matched to 510 healthy non-donors from the general population. The primary outcome was a hospital diagnosis of gestational hypertension or preeclampsia.

Gestational hypertension or preeclampsia developed in 15 (11%) of 131 pregnancies in the living donor group compared with 38 (5%) of 788 pregnancies in the control group. Compared with nondonors, the donors had a significant 2.4 times increased risk of gestational hyper-

tension or preeclampsia. The rates of preterm birth in the donor and non-donor groups were 8% and 7%, respectively, and the rates of low birth weight were 6% and 4%, respectively. No maternal deaths, stillbirths, or neonatal deaths were reported among the donors.

No increased rates of preterm birth and low birth weight observed.

Dr. Garg noted that the incidences of gestational hypertension, preeclampsia, and other maternal and fetal outcomes after donation were similar to those observed in the Ontario study.

In their NEJM report, he and his coauthors noted that the strengths of their study included a manual review of all perioperative donor charts, careful selection of similar donors and nondonors, and minimal loss to follow-up.

Additionally, their study population had access to a system of universal healthcare benefits whereby all healthcare encounters were recorded and the pregnancies of donors and non-donors

had similarly high levels of health surveillance, the investigators wrote.

The investigators acknowledged study limitations, including the fact that data regarding blood pressure, body mass index, renal function, and medication use during pregnancy were not available in their data sources. Another limitation was the lack of accurate racial information, and they noted that hypertension after kidney donation is more common among black than white donors. They pointed out, however, that 71% of Ontario citizens and 70% of donors are white.

“In addition, some donors may have had a genetic predisposition to kidney disease, which could have increased the risk of our primary study outcome among those in whom this condition developed.”

The latest study adds to recently published literature suggesting that living kidney donors are at elevated risk for health problems. For example, a Norwegian study published in Kidney International (2014;86:162-167) found that living kidney donors had a significantly elevated risk of end-stage renal disease and cardiovascular and allcause mortality compared with a control group of eligible kidney donors. n

Data Challenge Intravenous Iron Withholding NEW STUDY findings do not support guideline recommendations to withhold intravenous (IV) iron in hemodialysis (HD) patients hospitalized for infections “Guidelines for the treatment of anemia in chronic kidney disease have recommended caution, avoidance, or withholding of IV iron in the setting of active infection,” said lead investigator Julie H. Ishida, MD, a nephrology fellow at the University of California San Francisco. “However, these recommendations are based on limited data, and no data specifically support the recommendation to withhold IV iron in the setting of active infection.”

Using the U.S. Renal Data System database, Dr. Ishida and her colleagues identified 23,306 Medicare-covered adults on in-center HD who had

received IV iron within 14 days of their first hospitalization for bacterial infection in 2010. The researchers looked at the association between receipt of IV iron at any point from admission to discharge compared with no receipt of IV iron and all-cause mortality (within 30 days of admission and in 2010), readmission for infection within 30 days of discharge, and length of hospital stay.

Approximately 11% of the cohort had received IV iron at any point between admission and discharge, and 93% received their only dose on the day of admission. Receipt of IV iron was generally not significantly associated with age, dialysis vintage, comorbidities, or the infected organ system.

Of the 23,306 subjects, 2,684 died within 30 days of admission and 7,059

died in 2010, with a median follow-up time of 173 days. Receipt of IV iron was not significantly associated with any of the outcomes measures.

Researchers studied 23,306 HD patients who were hospitalized for bacterial infections.

“While we are not able to make a statement regarding the continued use of IV iron during a hospitalization for infection, our data do not support the practice of withhold IV iron upon admission for infection in hemodialysis patients,” Dr. Ishida said. n

11/21/14 9:04 AM

www.renalandurologynews.com DECEMBER 2014

Renal & Urology News 13

Exercise Decreases Odds of ESRD HIGHER LEVELS of physical activity are associated with a significantly decreased risk of end-stage renal disease (ESRD), according to researchers.

A team led by Tazeen Hasan Jafar, MD, of Duke-NUS Graduate Medical School in Singapore, analyzed data from a prospective cohort of 59,552 Chinese adults aged 45–74 years enrolled in the Singapore Chinese Health Study. Investigators collected information on physical activity using a structured questionnaire modeled after the European Prospective Investigation in Cancer (EPIC) study physical activity questionnaire. They defined physically active subjects as those who engaged in any moderate activities (such as brisk walking, bowling, bicycling on level ground) for 2 hours or more per week and strenuous aerobic activities (such as jogging, tennis, and bicycling on hills) 30 minutes or more per week.

During a median follow-up of 15.3 years, ESRD developed in 642 individuals and 9,808 participants died.

Compared with no physical activity,

Prophylactic SUI Surgery Effective A PROPHYLACTIC procedure may reduce the risk of post-operative stress urinary incontinence (SUI) in women undergoing repair of severe pelvic organ prolapse (POP), a new meta-analysis suggests.

The meta-analysis, by Priscila Katsumi Matsuoka, MD, of the University of São Paulo, and colleagues, included 7 trials involving

moderate or strenuous physical activity was associated with a 24% decreased risk of ESRD, after adjusting for age, sex, body mass index, and other potential confounders, Dr. Jafar’s group reported online ahead of print in Nephrology.

Moderate activity only for 2 hours or more per week was associated with a 19% decreased risk of ESRD and strenuous aerobic activity was associated with a 42% decreased risk.

The researchers also looked at the risk of ESRD or death. Compared with never engaging in physical activity, any physical activity was associated with a 15% decreased risk of ESRD or death.

Engaging in 2 hours or more of moderate activity per week was associated with a 12% decreased risk or ESRD or death, whereas strenuous aerobic activities were associated with a 27% decreased risk.

Of the 59,552 study participants, 13,200 (22%) engaged in habitual physical activity: 8,947 (15%) in moderate activity only and 4,254 (7%) in strenuous aerobic activity regardless of their status for moderate activity.

People may lower their ESRD risk by jogging or engaging in other strenuous activities.

The precise mechanism responsible for the independent relationship between physical activity and ESRD is not entirely clear, the investigators noted. Studies show that physical activity can decrease blood pressure and improve glycemia control. It also can improve cardiovascular health by enhancing endothelial function

directly through response to insulin, angiogenesis, and vascular regeneration via the up-regulation of endothelial nitric oxide production and other antioxidant enzymes. “It is entirely conceivable that the same would extend to the kidney vasculature leading to protection against glomerular filtration barrier defects, albuminuria, and declining kidney function,” the authors commented.

Dr. Jafar and her colleagues said a major strength of their study is the large sample size of a population-based cohort with near-complete followup, but the study had some limitations. One limitation was that physical activity was self-reported and did not include an objective assessment.

Another limitation was the absence of information on baseline kidney function, including serum creatinine or albuminuria. “This raises concern whether the observed association was mainly because individuals with preexisting CKD had already reduced their physical activity at baseline,” the researchers stated. n

© THINKSTOCK

Strenuous aerobic activities lowered the risk by 42% compared with no physical activity.

Low T Raises Atherosclerosis Risk MEN WITH type 2 diabetes are at higher risk of developing atherosclerosis if they have low rather than normal levels of testosterone, according to a study published in the Journal of Clinical Endocrinology & Metabolism (JCEM).

The study included 115 men younger than 70 years who had type 2 diabetes and no history of cardiovascular events. Compared with men who had normal testosterone levels (3.5 ng/mL or higher), those with low total testosterone levels (less than 3.5 ng/mL) had a significantly higher proportion of

patients with a carotid artery intimamedia thickness (IMT) of 0.1 cm or greater (80% vs. 39%), atherosclerotic plaques (68.5% vs. 44.8%), and endothelial dysfunction (80.5% vs. 42.3%).

They also had significantly higher levels of highly sensitive C-reactive protein (2.74 vs. 0.89 mg/dL). Results were similar for free testosterone.

The researchers identified the presence of atherosclerotic plaques using high resolution ultrasound and assessed endothelial function with brachial artery flow-mediated dilation.

In adjusted analyses, low total testos-

terone was independently associated with 8.4 times increased odds of greater IMT and 5.2 times increased odds of endothelial dysfunction, but not atherosclerotic plaques.

“The results of our study advance our understanding of the interplay between low testosterone and cardiovascular disease in patients with diabetes,” study author Javier Mauricio Farias, MD, of the Hospital Universitario Sanatorio Guemes in Buenos Aires, Argentina, said in a press release issued by the Endocrine Society, which publishes JCEM. n

women with severe POP and no SUI symptoms. Results showed that women who underwent retropubic midurethral sling surgery at the time of prolapse repair had a 91% decreased relative risk of SUI compared with women who did not have a prophylactic procedure, according to a paper published online ahead of print in the International Urogynecology Journal. n

News-Exercise_RUN1214.indd 13

Hemospermia Linked to High Uric Acid Levels HEMOSPERMIA may be linked to high uric acid levels, according to a report in Urology (2014;84:609-612).

Adel Kurkar, MD, and colleagues at Assiut University in Assiut, Egypt, studied 43 men who had 4–12 hemospermia attacks for 2–10 months before presentation, with no identifiable cause of the

hemospermia. Of these, 22 had hyperuricemia. The researchers compared these men with the 21 men with idiopathic hemospermia. Compared with the men who had idiopathic hemospermia, the hyperuricemia hemospermic patients had significantly higher serum uric acid levels (median 9.3 vs. 4.5 mg/dL), and they

were significantly younger (median 31.5 vs. 45 years) and had a higher proportion of patients who reported painful ejaculation (68.2% vs. 9.5%). Additionally, the hemospermia completely resolved in all men in the hyperuricemia group compared with only 25% of the idiopathic group within a mean of 2 months. n

11/20/14 5:00 PM

14 Renal & Urology News

DECEMBER 2014 www.renalandurologynews.com

Fewer Women than Men Receive HD FEWER WOMEN than men with end-stage renal disease (ESRD) are treated with hemodialysis, regardless of age group, according to findings from the ongoing Dialysis Outcomes and Practice Patterns Study (DOPPS).

A team led by Manfred Hecking, MD, of the Medical University of Vienna in Austria, studied 35,964 DOPPS patients from 12 countries and found that, overall, 59% of men with ESRD were on hemodialysis (HD) compared with 41% of women. In all 12 countries, fewer women than men were on HD. The average estimated glomerular filtration rate (eGFR) at HD initiation was higher in men than women, the researchers reported online in PLOS Medicine.

In addition, compared with women, men had a mean younger age (61.9 vs. 63.1 years) and they were less frequently obese and more frequently married.

The study also showed that the survival advantage that women have over men in the general population was markedly decreased in the HD population. “The finding that the general survival advantage for women is virtually lost for all adult age groups of individuals on dialysis is striking,” the authors wrote.

Dr. Hecking’s group explained that the finding that fewer women than men were on HD treatment in all DOPPS countries could in principle be related to differences in treatment modality for ESRD (in-center HD vs. home HD vs. peritoneal dialysis [PD]).

Both the U.S. Renal Data System and the Canadian Organ Replacement Registry, however, have shown that the incidence and prevalence of PD and home HD are higher in men than women, and more men had received a kidney transplant preemptively, the investigators pointed out.

Kidney disease severity in women may not be recognized by their caregivers.

“Whether men and women differ by dialysis initiation and chronic kidney disease care is perhaps the most important question raised by the present

ADT May Blacks with PCa Relapse Are More Likely To Regret Treatment Raise Cardiac Mortality

AMONG MEN who experience recurrence

problems after treatment. Among men

of prostate cancer (PCa), blacks may

with sexual problems after treatment,

be more likely than non-blacks to regret

the researchers observed no significant

being treated, according to a new study.

difference in the proportion of blacks

Brandon Arvin Virgil Mahal, MD, of

and non-blacks expressing treatment

Harvard Medical School in Boston,

regret. Among men without sexual prob-

and colleagues, studied 484 men (78

lems after treatment, however, 26.7%

black, 406 non-black) who experienced

of blacks expressed treatment regret

biochemical recurrence of PCa after

compared with 8.4% of non-blacks, a dif-

radical prostatectomy, external beam

ference that translated into a significant

radiotherapy, and brachytherapy.

4.7-fold increased odds of treatment

Results showed that 21.8% of black men

regret among blacks, in adjusted analy-

had treatment regret compared with

ses. The researchers say they believe

12.6% of non-black men, a difference

their findings support the notion that sex-

that translated into a significant 1.9

ual dysfunction is a ubiquitous concern

times increased likelihood of treatment

following PCa treatment among all men

regret among black men, Dr. Mahal’s

regardless of race “and in the presence

group reported online ahead of print in

of sexual issues after treatment, there

Prostate Cancer and Prostatic Diseases.

are no detectable differences in the rate

After adjusting for potential confounding

of regret across races.”

variables, however, black race no longer

“Treating physicians should ensure that

was significantly associated with an

patients are fully apprised of the pros

increased likelihood of treatment regret.

and cons of all treatment options in a cul-

In addition, the study found that racial

turally competent and relevant manner

differences in treatment regret may

in order to reduce the risk of subsequent

be mitigated by the presence of sexual

regret,” the authors concluded. n

News-Hemodialysis_RUN1214.indd 14

ANDROGEN-DEPRIVATION therapy (ADT) increases the risk of cardiacspecific mortality in prostate cancer (PCa) patients with a history of coronary artery disease, according to a new study.

A team led by Paul L. Nguyen, MD, of Harvard Medical School and the Dana-Farber Cancer Institute in Boston, retrospectively studied 5,077 men treated with brachytherapy with or without neoadjuvant ADT. The median duration of ADT was 4 months.

After a median follow-up of 4.8 years, the investigators observed no association between ADT and cardiac-specific mortality in men with no cardiac risk factors, Dr. Nguyen and his colleagues reported online ahead of print in BJU International. ADT, however, was associated with a statistically significant 3.3 times increased risk of CSM in patients with congestive heart failure (CHF) or a prior myocardial infarction (MI) in adjusted analyses. In this subgroup of patients, the 5-year cumulative incidence of CSM was 7% for those who received ADT versus 2% for those who

study,” Dr. Hecking and his colleagues concluded. “This question is not novel, as national data have been available for decades, but may not previously have been asked as clearly as by the present analysis with a large sample size and international perspective.”

In a discussion of study limitations, the authors noted that their analyses show associations, not causation, “and can thus merely hint at the mechanism that render mortality rates similar in men and women on hemodialysis.” In addition, their descriptive findings of sex disparity in the use of HD cannot answer why the prevalence of HD is higher among men than women. Psychosocioeconomic factors could be responsible, but it is also possible that the severity of kidney disease in women is not recognized by their caregivers or that women are less aware of their disease and the degree of its severity, or they are more reluctant to undergo treatment. n

© SHUTTERSTOCK

Study shows that 59% of men with end-stage renal disease were on hemodialysis versus 41% of women.

did not. Thus, administering ADT to 20 patients with CHF or prior MI could result in 1 cardiac death, according to the researchers.

The authors concluded that their results should encourage clinicians to consider the cardiac health of their patients when evaluating the benefits of ADT for prostate cancer.

The new study lends additional credence to concern about adverse cardiac effects of ADT that culminated in a joint statement from the American Urological Association, American Heart Association, American Cancer Society, and American Society for Radiation Oncology, which cautioned that the therapy might be associated with cardiac harm, Dr. Nguyen’s group stated.

Dr. Nguyen and his collaborators noted that despite the demonstrated association between ADT and cardiac harm, “providers must not lose sight of the strong evidence that supports the use of ADT to reduce prostate cancer mortality … in men with aggressive disease.”

At this point, the investigators noted, they do not advise withholding ADT from any patient with aggressive PCa for whom the results of randomized trials have shown a survival benefit of ADT, even if the patient has a history of heart disease. n

11/21/14 9:20 AM

www.renalandurologynews.com

DECEMBER 2014

Renal & Urology News 15

AKI Ups Risk of Early Readmission Patients who suffer hospital-acquired acute kidney injury may warrant closer follow-up Hospital Readmission Rates: AKI vs. No AKI Patients who suffer acute kidney injury while hospitalized have higher rates of early readmission than those who do not, according to a new study.

25 20 15

■ Patients

10

■ Patients

with AKI

without AKI

5 0

15%

11%

30-day

20%

15%

60-day

23%

Readmission Rate

18%

90-day

Source: Koulouridis I et al. Hospital-acquired acute kidney injury and hospital readmission: A cohort study. Am J Kidney Dis. 2014; published online ahead of print.

PATIENTS WHO suffer hospitalacquired acute kidney injury (AKI) are at higher risk of early hospital readmission, according to a new study.

Investigators led by Bertrand L. Jaber, MD, MS, of Tufts University School of Medicine in Boston, studied 22,001 hospitalized adults, of whom 3,345 (15%)

experienced AKI during the index hospitalization. The 30-, 60-, and 90-day hospitalization rates were 15%, 20%, and 23%, respectively, for the AKI patients compared with 11%, 15%, and 18% for the non-AKI patients, respectively.

In adjusted analyses, the AKI patients had a significant 21%, 15%, and 13%

Halting mRCC Drugs Induces Tumor Flare

months. The reasons for treatment discontinuation were disease progression (61.9% of cases), toxicity (22.2%), and sustained response (15.9%).

The median GR1 was 0.16 cm per month and the median GR2 was 0.70 cm per month, Dr. Iacovelli’s group reported online ahead of print in European Urology. In the overall population, the median tumor flare was 0.55 cm per month, and differed according to the reason for discontinuation.

It was 1.66 cm per month for disease progression, 0.95 cm per month for toxicity, and 0.15 cm per month for sustained response. In adjusted analyses, tumor flare was associated with an 11% increased risk for death from the time of treatment discontinuation.

Patients with GR1 less than the median had significantly greater overall survival than patients with GR1 greater than or equal to the median (51.6 vs.

12.3 months). Patients with GR2 less than the median had significantly greater overall survival than those with GR2 greater than or equal to the median (51.6 vs. 15.1 months).

The study provides the first clinical evidence that discontinuing sunitinib or pazopanib results in acceleration of tumor growth rate, and thereby negatively affects the prognosis of mRCC patients, the researchers stated. ■

DISCONTINUING sunitinib and pazopanib treatment may result in acceleration of tumor growth rate and induce tumor flare in patients with metastatic renal cell carcinoma (mRCC), which can lead to worse survival.

Roberto Iacovelli, MD, of Gustave Roussy in Villejuif, France, and colleagues studied 63 patients with mRCC treated with first-line sunitinib or pazopanib—both tyrosine kinase inhibitors—at standard dosages. All had discontinued treatment because of disease progression, intolerable toxicity, or sustained response (partial response/ stable disease). Subjects had their tumor growth rates evaluated immediately before treatment (GR1) and after immediately treatment discontinuation (GR2).

The investigators calculated tumor flare by substracting GR1 from GR2). The main study outcome was overall survival.

The median duration of treatment was 9.3 months. The median progression-free survival was 11.1 months, and the median overall survival was 41.5

AKI-news_RUN1214.indd 15

increased odds of readmission within 30, 60, and 90 days, respectively, compared with non-AKI patients, the researchers reported online ahead of print in the American Journal of Kidney Diseases.

In a propensity score–matched cohort of 5,912 patients, Dr. Jaber’s group found that AKI was associated with a significant 16% increased odds of readmission within 30 days and a nonsignificant 11% and 8% increased odds at 30 and 90 days, respectively.

The AKI group was more likely to be rehospitalized within 30 days for cardiovascular-related conditions, particularly heart failure and myocardial infarction.

“Our study suggests that AKI might be an unrecognized determinant of short-term hospital readmission and calls for the systematic study of transitions of care among hospitalized patients who experience an episode of AKI, with the ultimate goal of preventing or decreasing unplanned rehospitalizations,” the authors wrote.

The researchers concluded that their study supports the hypothesis that mild forms of hospital-acquired AKI portend increased odds of hospital readmissions within 30 days. “Whether the relationship between hospital-acquired AKI and hospital readmission is causal or associative, AKI is a compelling risk factor for this unwarranted and costly outcome,” they wrote. “If our findings are externally validated, the identification of mild episodes of hospitalacquired AKI should compel physicians to exercise heightened vigilance with a focus on timely follow-up of such patients in the ambulatory setting.”

Dr. Jaber and his colleagues acknowledged important study limitations. They noted that the study was conducted at a single acute-care facility, “so the generalizability of the results may be narrowed.” The researchers lacked information on socioeconomic status, which might have affected transitions to care services and hospital readmission risk. ■

Renal Hyperfiltration May Predict Higher Mortality RENAL HYPERFILTRATION (RHF) may

the Journal of the American Society of

have potential as a novel marker of all-

Nephrology. The investigators defined

cause and cardiovascular mortality in

RHF as an eGFR above the 95th percen-

apparently healthy people, a new South

tile after adjusting for sex, age, muscle

Korean study suggests.

mass, and history of diabetes and/or

A team led by Hyung-Jin Yoon, MD,

hypertension medication use.

of Seoul National University College of

The investigators also examined the

Medicine, studied 43,503 adults who

association between RHF and all-cause

underwent voluntary health screening

mortality according to smoking status.

at Seoul National University Hospital

RHF was associated with a significant

from March 1995 to May 2006. At the

58% and 73% increased risk of all-

time of screening, the study popula-

cause mortality in nonsmokers and for-

tion had a mean age of 49.2 years.

mer smokers, respectively, but was not

All subjects had a baseline estimated

significantly associated with all-cause

glomerular filtration rate (eGFR) of 60

mortality in current smokers.

mL/min/1.73 m or higher. A total of 2

Additionally, the study showed that

1,743 deaths occurred during a median

RHF was 31% more likely among individ-

follow-up of 12.4 years.

uals in the highest versus lowest quartile

After adjusting for known risk factors,

of lean body mass, after adjusting for

including smoking, subjects with RHF

potential confounders such as sex, age,

had a 37% increased risk of all-cause

smoking, regular exercise (exercising

mortality and a 66% increased risk of

more than 30 minutes at least 3 times

cardiovascular mortality compared with

per week), and regular alcohol use

those who did not have RHF, Dr. Yoon’s

(defined as consumption of alcoholic

group reported online ahead of print in

beverages at least once a week). ■

11/21/14 9:33 AM

20 Renal & Urology News

DECEMBER 2014 www.renalandurologynews.com

Study: PD May Offer Better Early Survival than HD In a study, the survival advantage was evident for up to 2–3 years treated analysis, with no significant difference in adjusted survival thereafter, and up to 2 years in the intent-to-treat analysis, with no difference in adjusted survival thereafter, Dr. Kumar and her colleagues stated in their report.

Dr. Kumar’s group pointed out that other studies have demonstrated that

© HUBERT RAGUET / SCIENCE SOURCE

NEW STUDY FINDINGS confirm previous research showing an initial survival advantage with peritoneal dialysis (PD) versus hemodialysis (HD), even among patients who have received pre-dialysis care and those starting HD with an arteriovenous fistula or graft.

In a study, patients with end-stage renal disease who started on peritoneal dialysis were more likely to be alive at 1 year compared with those who started on hemodialysis.

The study included 1,003 propensity-matched pairs of incidental PD and HD patients receiving care in the Kaiser Permanente Southern California health system. The HD cohort included only those patients who received dialysis with an arteriovenous fistula or graft during the first 90 days of the study. The researchers excluded from final analyses HD patients who used a central venous catheter at any time during the first 90 days of dialysis. The investigators compared survival using both as-treated and intent-to-treat analyses.

Compared with PD patients, HD patients had a 2.4 and 2.1 times greater risk of death at 1 year in astreated and intent-to-treat analyses, respectively, the investigators, led by Victoria A. Kumar, MD, of Southern California Permanente Medical Group in Los Angeles, reported in Kidney International (2014;86:1016-1022).

PD was associated with a survival advantage for up to 3 years in the as-

News-PD-HD_RUN1214.indd 20

PD patients experience a lower risk of death in the first 1–2 years after start of dialysis. Explanations include the lack of pre-dialysis care and the use of central venous catheters in HD patients.

Another possibility is that PD patients have better preservation of residual renal function, according to the researchers. “Although higher residual renal function during the first few years on PD could explain our results,” they wrote, “changes in peritoneal membrane structure over time along with reduced ultrafiltration capacity could explain why PD patients lose their survival advantage after the first few years on dialysis.”

Dr. Kumar and her colleagues noted that the strengths of their study include a large and diverse PD cohort and a relatively long follow-up time.

In addition, patients appeared to be well matched in terms of baseline disease burden and demographics.

A major limitation to their study was the absence of data regarding residual

renal function at the time of dialysis initiation. “The authors cannot exclude that baseline residual renal function was higher in PD patients than in matched HD patients, potentially conferring a survival benefit to the PD cohort,” they wrote.

In an accompanying editorial, Christos P. Argyropoulos, MD, and Mark L. Unruh, MD, of the Division of Nephrology in the Department of Internal Medicine at the University of New Mexico in Albuquerque, commented that the study by Dr. Kumar’s group “is an important addition to the evolving literature concerning the relative outcomes of dialysis modalities and establishes a methodological benchmark against which future studies on the same topic should be measured.”

At the 51st Congress of the European Renal Association–European Dialysis and Transplant Association, Boris Bikbov, MD, of A.I. Evdokimov Moscow State University of Medicine and Dentistry in Moscow, and colleagues reported on a study showing that PD as the initial dialysis modality is associated with a survival advantage over HD during the first year, but HD may offer better survival long term (see July 2014 issue of Renal & Urology News). The study included 11,021 incident HD and PD patients.

The researchers classified patients into 4 groups according to initial modality and long-term (duration more than 30 days) transfer to another modality: HD only, PD only, HD to PD, and PD to HD. PD-only patients had a significantly higher survival rate than HD-only patients at 1 year (82% vs.

76.1%), but a significantly lower rate at year 5 (33.7%) vs. 54.5%). Survival rates did not differ significantly between the groups at years 2, 3, and 4.

Among those switched from HD to PD, the rates were 87.7%, 75.9%, 63%, 49.3%, and 42%, respectively. Among patients switched from PD to HD, the survival rates at 1, 2, 3, 4, and 5 years were 96%, 89.7%, 82%, 74.6%, and 67.5%, respectively.

“Our results suggest that PD was the preferable initial dialysis modality that could be later switched to HD,” the authors concluded. n

ACP Issues Kidney Stone Guideline THE AMERICAN COLLEGE of Physicians (ACP) has unveiled a new guideline for preventing recurrent kidney stones in adults.

For patients who have had 1 or more prior kidney stone episodes, the guideline recommends increased fluid intake spread throughout the day to achieve at least 2 liters of urine per day. The guideline also recommends pharmacologic monotherapy with a thiazide diuretic, citrate, or allopurinol to prevent nephrolithiasis in patients with active disease in which increased fluid intake fails to reduce stone formation.

In addition, according to the guideline, which was published in Annals of Internal Medicine (2014;161:659-667), evidence shows that patients who decreased intake of soda acidified by phosphoric acid had decreased kidney stone recurrence. “Clinicians should encourage patients to avoid colas as opposed to fruit-flavored soft drinks, which are often acidified by citric acid,” the guideline stated.

Increased fluid intake throughout the day to achieve 2 L of urine daily is recommended.

The guideline, which was developed by the ACP’s Clinical Guidelines Committee, is based on a systemic evidence review and an evidence report sponsored by the U.S. Agency for Healthcare Research and Quality.

The evidence is applicable primarily to calcium stones.

The guideline document states that current evidence from randomized trials is insufficient to evaluate the benefits of determining stone composition and urine and blood chemistry related to the effectiveness of treatment.

“The guidelines committee is aware that observational data show an association of stone composition and biochemistry with stone recurrence; moreover, physiologic knowledge suggests that interventions targeting stone composition, biochemistry, or both can favorably alter biochemical composition that leads to stone formation,” the document noted. n

11/20/14 6:04 PM

www.renalandurologynews.com

DECEMBER 2014

Renal & Urology News 21

Men’s Health Update Short Takes Caffeine Found to Improve Muscle Strength The effects of caffeine on muscle strength have been equivocal, and this is thought to be based on the muscle groups that have been evaluated. A recent study looked maximal voluntary contraction strength in resistance-trained men randomized to testing with 6 mg/kg of caffeine (equivalent to about 3–4 cups of coffee) versus placebo. The men who received caffeine experienced significantly increased muscle performance, according to a report in the Journal of Strength Conditioning Research (2014;28:3239-3244). Both upper and lower body muscle groups were noted to improve with caffeine. While it seems that larger muscle groups may respond more favorably to caffeine, the influence on muscle group size remains in question.

Study Correlates Testosterone Levels with Symptoms Investigators from Baylor College of Medicine in Houston evaluated the correlation between hypogonadal symptoms and serum testosterone levels using the ADAM questionnaire. In middle-aged men, investigators observed an increased prevalence of symptoms within a testosterone range of 320–375 ng/dL and symptom clusters at levels of 300 ng/dL or less, according to a report published online ahead of print in Urology. The authors, led by Larry I. Lipshultz, MD, concluded that a “distinct constellation of hypogonadal symptoms exists at various serum testosterone levels. Consequently, identification of the thresholds for specific symptom management will be critical in establishing patient-centered treatment algorithms.”

Online Resources Could Aid Weight Loss Obese men are more likely to have diet-related chronic disease risk compared with their female counterparts. To investigate optimal mechanisms for weight loss, researchers provided obese men with self-help paper-based resources with or without online support. With 6-month follow-up, those receiving online support had reduced fat and carbohydrate intake compared with controls. These preliminary data indicate that online dietary support may help men improve their diet and lose weight, according to report in Obesity Research & Clinical Practice (2014;8:e476-e487).

Chinese Herb Found to Ease Knee Pain in Elderly Men The Chinese herbal medication guilu erxian jiao (GEJ) has

BY JAIME LANDMAN, MD

University of California, Irvine, Department of Urology

More Physical Activity May Cut CP/CPPS Risk H

igher levels of physical activity may lower the risk of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in middle-aged and older men, a new study suggests.

Ran Zhang, MD, ScD, MPH, of the Harvard School of Public Health in Boston, and colleagues conducted a prospective cohort study of men who participated in the Health Professionals Follow-up Study from 1986 to 2008. The study included 20,918 men who filled out questionnaires asking about leisure-time physical activity in 1986 and completed all CP/CPPS questions on a 2008 questionnaire. Researchers calculated a National Institute of Health Chronic Prostatitis Symptom Index pain score based on responses to the 2008 questionnaire. Men who had a pain score of 8 or higher were considered to have CP/CPPS. This group included 689 men.

In multivariate analysis, men who had more than 35 MET-h/wk of leisure-time physical activity had 28% decreased odds of CP/CPPS than men whose leisuretime physical activity totaled 3.5 MET-h/wk or less, according to an online report in Medicine & Science in Sports & Exercise.

The researchers noted that this study is the first large scale and most comprehensive study to date looking at this association.

Sleeping Around May Protect Against Prostate Cancer M

en who have plenty of sexual partners in their lifetime may be at lower risk of prostate cancer (PCa), new findings suggest.

A team led by Marie-Élise Parent, PhD, of the University of Montreal School of Public Health, studied 1,590 histologically confirmed PCa cases and 1,618 population controls frequency matched to cases by age. Men who had more than 20 female sexual partners in their lifetime had a 28% decreased risk of PCa compared with those who slept with only 1 woman, the researchers reported online in Cancer Epidemiology. The study found no association between sexually transmitted infections and PCa. Higher ejaculation frequency is a possible explanation for the reduced risk associated having numerous sexual partners, Dr. Parent’s group stated.

been shown in studies to be safe. It is commonly used Researchers in Taiwan recently randomized 42 elderly men with knee osteoarthritis to treatment with GEJ versus no treatment. Through 12 weeks of treatment, GEJ supplementation resulted in increased selected lower extremity muscle strength and diminishment of articular pain, the investigators reported in Evidence-Based Complementary and Alternative Medicine (2014;297458). The authors, led by Der-Yuan Chen, MD, reported no adverse effects and no changes in liver or renal function tests, but cautioned that longerterm studies were needed.

MensHealth_RUN1214.indd 21

MEDISTAT

to slow aging and to ease knee pain from osteoarthritis.

10.6

The prevalence of selfreported kidney stones among men, according to a cross-sectional analysis of responses to the 2007–2010 National Health and Nutrition Examination Survey.

Source: Scales CD Jr, et al. Prevalence of kidney stones in the United States. Eur Urol. 2012;62:160-165.

IMAGES: © THINKSTOCK

Please visit us at www.renalandurologynews.com for the latest news updates from the fields of urology and nephrology

11/20/14 4:28 PM

26 Renal & Urology News

DECEMBER 2014 www.renalandurologynews.com

Practice Management Patient portals, which are required to be eligible for Meaningful Use Stage 2, can be timesavers for physician’s offices. BY TAMMY WORTH or make appointments, that means 2 fewer kinds of calls coming into the practice every day.

And even when it doesn’t literally save work, portals can still help manage time. Instead of taking calls during the day, physicians can allow patients to email and then get to them when they have time to devote to the task.

Setting one up If an office doesn’t have a patient portal, the best time to get one is when setting up electronic medical records (EMR). Portals owned and integrated

by EMR vendors are the easiest to set up, Douglass said. The ease and cost of patient portal integration can be aspects to include in EMR vendor selection criteria.

The best way to determine what components to have in the portal is to understand what you want to accomplish with it. Setting one up to comply with the meaningful use requirements will simply require that patients can read and transfer health information to third parties.

Douglass said that must-have features include partial patient chart view access that includes lab and test results, medication lists, immunization lists, diagnoses, and medication allergies. A portal should also include a visit summary and secure patient messaging.

A portal can be used as a direct line to patients, not only to send individual messages to patients, but also to send blast messages.

January 2014 study, Kaiser Permanente researchers found that patients with diabetes who got refills of statin medications exclusively through an online portal reduced medication use and increased medication adherence and cholesterol. Patients in the study regularly used an average of 6 medications.

Portals can also be timesavers for a physician’s office. For instance, if a portal allows patients to refill medications

PM_RUN1214.indd 26

Beyond that, a portal may be used to increase patient engagement or save time by enabling patients to make medication refill requests, schedule appointments, obtain online statements, pay bills, and flag their chart if they see inaccurate information.

Offices can also use the portal as a direct line to patients, said Angela Dangelo, patient portal specialist with the consulting firm Beacon Partners. It

© THINKSTOCK

T

he healthcare industry has been working toward greater communication between patients and providers for years. It is well established that patients who are more involved in their healthcare have better outcomes.

Experts have been recommending greater patient engagement, and now the federal government is requiring it.

To be eligible for Meaningful Use Stage 2, providers have to use patient portals. Guidelines require providers to have more than 5% of their patients send an electronic message to a physician (which can be done through portals) and view, download, or transmit to another party their health information during the reporting period.

Matthew Douglass, co-founder and vice president of platform at Practice Fusion, said providers should be embracing this patient engagement tool as much as possible. “The most crucial tool in a doctor’s 21st century toolbelt (for 2-way communication with the patient) is the online patient portal,” Douglass said.

“This empowers the patient and her caregivers with access to her most recent medical information and provides an ability for the physician, patient, and care team to communicate securely.”

Aside from meeting meaningful use standards, portals may be able to help improve patient outcomes. In a

Online portals empower patients and their caregivers.

can be used not only to send individual messages to patients, but could be used to blast messages like “It’s time to get a flu shot” to groups of patients, she said.

Staffing The CMS set the bar relatively low for patient engagement on a portal at 5%.

Most providers who put the time and energy into building a portal, however, will want more than this. Some key staffing measures can aid in that goal.

To get the most out of the portal, Dangelo recommends ensuring an appropriate governance structure is in place to develop an implementation strategy and define goals, in addition to providing oversight and decision-making during the implementation process.

Equally important is the development of a well-trained and experienced technical support team. This could be part of an organization’s existing support team that is specifically trained on the portal and related systems or an external group brought in specifically to fill this role. “I have seen organizations that outsource all of their patient portal support needs,” she said. “It depends on what works for your organization.” Either way, the support team should consist of individuals highly

skilled in both customer service excellence and patient portal support.

Physicians should be involved in the process from a marketing standpoint.

They can play a huge role in encouraging patient engagement through a portal and recommending that patients use it.

Be creative Patient portals are truly a new way to think about care and communication with patients. One way to get patients to think about using them is to leverage the traditional patient contact points to promote the tool.

Aside from physicians encouraging patients to use the tool, office staff can put a message on the phone messaging system so patients hear it when waiting on the line. A reminder can be put on patient bills. Douglass recommends creating a “placeholder” patient and walking patients through the enrollment steps while they are in the office.

“You have to think about your marketing strategy,” Dangelo said. “You can put a portal out there and it can be great, but if patients don’t know it’s there, it’s meaningless.” n Tammy Worth is a freelance medical journalist based out of Blue Springs, MO.

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27 Renal & Urology News

DECEMBER 2014 www.renalandurologynews.com

■ Special to Renal & Urology News

CROWNWeb Updated to Improve Data Entry Efforts and Support Automation of CMS Forms New enhancements include a “save” button on each Clinical screen, allowing users to stop clinical data entry efforts at any point, save the information entered, and return at a later date to finish

BY ONIEL DELVA, BA FOR YEARS, the Centers for Medicare & Medicaid Services (CMS) has worked with members of its CROWNWeb support teams to review federal rules and regulations pertaining to electronic data submission; system and business requirements; and user feedback to identify necessary updates and enhancements to the agency’s CROWNWeb data collection system.

As part of an effort to help ensure that CROWNWeb contains the features and functionality necessary for users to meet administrative and clinical data submission requirements, CROWNWeb has seen four major revisions since its National Release in June 2012. While most of the changes to CROWNWeb have been to provide “behind the scenes” support to improve the system’s data processing capabilities, or to enable data reporting fields for annual use (i.e., the enabling of the Facility Attestation fields each year to support the End-Stage Renal Disease Quality Incentive Program), these releases have also introduced new functionality that has streamlined how users are able to gather and report data in CROWNWeb. A Step in the Right Direction CMS has implemented two releases of the CROWNWeb system in 2014—CROWNWeb Version 4.4 in May and CROWNWeb Version 4.5 in September—with a third release planned for December 2014.

CROWNWeb Version 4.4 and CROWNWeb Version 4.5 have been well received by users, because both releases boasted many features requested by facility-level users since the system originally debuted as part of a phase-in pilot in 2009.

CROWNWeb Version 4.4 introduced the bulk of the requested features—

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most of which were applied to the system’s Clinical screens. CROWNWeb 4.5 presented facility-level users access to Missing Forms and Saved Status reports that helped facilities identify and resolve missing CMS-2728 Medicare Enhancement and/or Patient Registration and CMS-2746 ESRD Death Notification forms.

CMS constantly receives requests to include additional functionality in CROWNWeb. “Can you add the ability to save data entries on the Clinical screens in CROWNWeb?” “Can CROWNWeb present the ability to indicate that lab data was not drawn for a particular patient during a reporting month?” “Can we have access to Missing Forms reports at the facilitylevel?” These are examples of some of the questions submitted to CMS that resulted in practical changes to the functionality of the system.

Before any enhancement or change request can be applied to CROWNWeb, it is reviewed for user and system impact, scored to determine both the level of importance and potential implementation timeframe, and tested to determine if the development meets the identified need. If the request passes these criteria, only then may the updates be approved by CMS for release. (See Figure 1 for a snapshot of the CROWNWeb Updates review and deployment process.)

The interface of CROWNWeb is often updated in accordance with user requests. After going through CMS’ detailed review and testing process, many fields, menus, and selections in CROWNWeb were simplified (especially on the Clinical screens) and fields have been added or removed to help reduce burden and improve data quality. The following updates were added to CROWNWeb over the two release cycles in 2014:

Enhancement List • CMS and CROWNWeb business requirements team review enhancement requests.

• CROWNWeb application development and testing teams review enhancement list.

• Enhancement list is prioritized based on feedback from CROWNWeb support teams.

• Final enhancement list and support needs are defined, and presented to CMS for approval.

Enhancement Testing and Deployment • CROWNWeb application development team begins programming.

• CROWNWeb application development team engages in multiple builds and testing.

• CROWNWeb application development team demonstrates the CROWNWeb application.

• The CROWNWeb application is released.

Figure 1: Overview of CROWNWeb enhancement review and deployment process.

• Clinical “Save” button • Clinical “N/A” (Not Available) check­boxes • Missing Forms reports • Saved Status reports • Framework to support electronic submission of CMS forms

Clinical “Save” Button For years, CROWNWeb has featured “Save” buttons on the CMS-2728 and CMS-2746 screens to allow users to save their work for each form. Users can then return and complete the forms before printing them for necessary signatures and/or to include with patients’ records. CROWNWeb was updated to feature a “Save” button on each Clinical screen—allowing users to stop clinical data entry efforts at any point, save the information entered, and return at a later date to finish. Saved data can be updated at any time, provided that the clinical month is still open.

When a user saves clinical data, system validation is not performed.

Instead, the system conducts its data validation at the time of submission.

It presents error messages for missing and/or unselected entries, and warning messages for data that is outside of a predetermined or expected

range. Further, in order for a facility to comply with CMS’ data submission requirements, its users must work to submit all missing and saved clinical data entries before the closure of that reporting month. (See Table 1 for the 2015 CROWNWeb clinical closure months announced by CMS on September 19, 2014.)

Clinical N/A Selections Beginning with CROWNWeb 4.4, all fields on the Clinical screens in CROWNWeb require entries. This means that users must enter the requested data if available or indicate if the information is not available for a particular patient during a reporting month CROWNWeb presents users with two means of indicating that lab values or patient details requested on the Clinical screens are not available for a specific patient. For patients with no laboratory values for an entire clinical month, users can check a “Master N/A” checkbox. This indicates that the facility has “No Clinical Data Available For All Collection Types”— the facility never treated the patient during a reporting month due to death or a discharge at the start of the reporting month. Alternately, users can make

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field-by-field “N/A” selections to note that the patient was treated, but specific data are not available.

Challenges and Setbacks One of CROWNWeb’s most requested enhancements is the ability for clinical fields to automatically carry over from month to month. Conceptually, facilities would enter the data once and CROWNWeb would allow that entry to automatically display the following month. This logic has been a part of CROWNWeb’s Vascular Access screen since 2012. Knowing that patients’ accesses infrequently change, CMS designed CROWNWeb to allow access data to carry over from month to month as long as that data is reviewed each month and updated as needed. Recognizing the benefit of this feature, CMS looked into the possibility of expanding this feature to some of the fields on the Hemodialysis and Peritoneal Dialysis Clinical screens.

The ability for data entered in the “Height,” “Height Unit of Measure,” and “Vaccination” areas on the Clinical screens to carry over was intended to be added as part of the Version 4.4

release in May 2014. However, an error was identified that prevented the feature from operating as designed. After working with its CROWNWeb support teams, CMS was able to identify the root cause of the error and plan a fix to be rolled out as part of the CROWNWeb 4.6 release scheduled for December 2014.

Automating CMS Form Submissions In September 2014, CMS laid the foundation for CROWNWeb to support the electronic population and submission of CMS-2728 forms. This feature helps open up the possibility of reducing manual data entry in CROWNWeb for all users (and associated manual entry errors), and will be expanded to include the automation of the CMS-2746 form in December 2014. With these updates, CMS has provided a platform to allow CMS2728 and CMS-2746 forms to be electronically uploaded in a saved status to be completed by a facility representative or received by the facility in a submitted status. The automation of CMS forms is still in the early stages of development, and organiza-

Statin Plus Metformin May Reduce PCa Relapse Risk CONCOMITANT USE of statins and metformin may decrease a prostate cancer (PCa) patient’s risk of biochemical recurrence (BCR) following radical prostatectomy compared with the use of either medication alone, researchers concluded.

Matthew Danzig, MD, and collaborators at the Herbert Irving Cancer Center, Columbia University College of Physicians and Surgeons, New York, retrospectively studied 767 diabetic men (median age 63 years, median Gleason sum 7, median preoperative PSA 6.1 ng/mL) undergoing radical prostatectomy for PCa. Of these, 76 (9.9%) were users of statins only, 56 (7.3%) were users of metformin only, and 42 (5.5%) used both statins and metformin. The cohort had a median postoperative follow-up period of 27 months.

In multivariable analysis, statin use alone or metformin use alone was not significantly associated with BCR-free survival, but dual use of statins and metformin was associated with a significant 80% decreased risk of BCR than would be expected from each medication’s independent effects, the

CrownWeb_RUN1214.indd 28

investigators reported online ahead of print in Prostate Cancer and Prostatic Diseases.

Dr. Danzig’s group noted that a synergism between statins and metformin is biologically plausible based on the current understanding of their diverse molecular pathways of action.

The study is not the first to demonstrate possible synergism between statins and metformin as it relates to PCa. In a study of male 5,042 type 2 diabetics seen in the Veteran Administration healthcare system, Donna M. Lehman, PhD, of the University of Texas Health Science Center in San Antonio, and colleagues found that metformin use was associated with a significant 31% decreased risk of PCa among men on statins, according to a paper published in Diabetes Care (2012;35:1002-1007).

Results also showed that metformin was associated with a significant 2.1 times increased PCa risk among patients not on statins. Patients taking both metformin and statins had a significant 68% decreased risk of PCa compared with men not taking either medication. n

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Clinical Month(s)

Date of Closure for Clinical Submissions

October 2014

January 31, 2015 at 11:59 p.m. ET

November 2014

January 31, 2015 at 11:59 p.m. ET

December, 2014

January 31, 2015 at 11:59 p.m. ET

January 2015

March 31, 2015 at 11:59 p.m. ET

February 2015

April 30, 2015 at 11:59 p.m. ET

March 2015

May 31, 2015 at 11:59 p.m. ET

April 2015

June 30, 2015 at 11:59 p.m. ET

May 2015

July 31, 2015 at 11:59 p.m. ET

June 2015

August 30, 2015 at 11:59 p.m. ET

Table 1: 2015 CROWNWeb clinical closure months announced by CMS on September 19, 2014.

tions that electronically report data into CROWNWeb via the system’s Electronic Data Interchange (EDI) are currently exploring how they can configure their respective systems to support this feature.

For More Information For more information on CROWNWeb and the system’s features, visit the Project CROWNWeb website at http://projectcrownweb.org/, or visit the CMS CROWNWeb website at https://www.qualitynet.org/ and click on the ESRD tab. n

The work on which this publication is based was performed under Contract Number HHSM-500-2011-00157G, titled “CROWNWeb Outreach, Communication, and Training,” funded by the Centers for Medicare & Medicaid Services, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. Publication Number: FL-OCT-OCT-10312014-02

Conscious Sedation Found Safe for Renal Cryoablation LOCAL ANESTHESIA with conscious

hospital stay (1.95 vs. 1.08 days),

sedation (LACS) is safe and effective for

Dr. Landman’s group reported online

patients undergoing percutaneous renal

ahead of print in Urology.

cryoablation for small renal masses,

In addition, the rate of immediate

and, compared with general anesthe-

failure and disease recurrence did not

sia, has the advantage of decreased

differ significantly between the GA and

procedure time and shorter hospital

LACS groups.

stays, according to a new study.

In a retrospective study, Jaime

The researchers noted that, to their knowledge, the study is the first

Landman, MD, of the University of

to assess differences in outcomes

California Irvine, and colleagues

between GA and LACS during PRC.

analyzed data from 235 patients who

The study had several limitations,

underwent percutaneous renal cryoab-

including its retrospective design, which

lation (PRC). Of these, 153 had LACS

makes it prone to selection bias, Dr.

and 82 had general anesthesia (GA).

Landman and his colleagues stated. In

The 2 groups were similar with respect

addition, the authors noted that their

to age, gender, body mass index,

early experience with PRC began with

and other clinical characteristics. The

the GA approach and transitioned

mean follow-up times for the GA and

to LACS with increasing expertise

LACS groups were 37 and 21 months,

and technologic improvements.

respectively, a significant difference

“Accordingly, the learning curve over

between the groups.

time may be a source of bias in compar-

The GA group had a significantly

ing the GA and LACS groups.” Moreover,

longer mean procedure time than

the longer follow-up of the GA group

the LACS group (133 vs. 102 min-

may be a source of bias with respect to

utes) and a significantly longer mean

the treatment failure outcome. n

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Study: Diabetes Mellitus Raises RCC Death Risk DIABETES MELLITUS (DM) is independently associated with decreased overall and cancer-specific survival in patients who undergo surgery for clear-cell renal cell carcinoma (ccRCC), according to a new study.

A team at Mayo Clinic in Rochester, Minn., led by R. Houston Thompson, MD, reviewed data from 1,964 patients who had surgery for sporadic, unilateral ccRCC from 1990 to 2008. Of these, 257 (13%) had DM. The researchers matched these patients 1:2 to referent patients without diabetes according to clinicopathological and surgical features. The median postoperative follow-up was 8.7 years. At a median of 2.6 years postoperatively, 149 patients had died of RCC. The researchers excluded from their analysis of cancerspecific survival 23 patients who die of an unknown cause.

On multivariable analysis, DM was independently associated with a significant 55% increased risk of cancerspecific mortality and a significant 32% increased risk of all-cause mortality, the

researchers reported in The Journal of Urology (2014;192:1620-1627). DM was not associated with risk of progression.

“These findings underscore the importance of considering the effect of DM among other comorbidities on outcomes during risk stratification in RCC,” the authors concluded. “They also support the hypothesis regarding the potential influence of the hyperglycemic and hyperinsulinemic DM states on ccRCC behavior and as such they warrant further investigation.”

The researchers explained that “high plasma insulin results in increased hepatic production of IGF-1, which has a central driving role in cell proliferation and differentiation, protecting against apoptosis.”

Dr. Thompson’s group noted that the strengths of their study include a substantial follow-up, but the study had some limitations, including the retrospective design, which precluded the ability to definitively test a causal relationship between DM and decreased overall survival. n

Novel Gene-Based Tool Predicts Bladder Cancer Recurrence A NOVEL GENOMIC-BASED signature

According to the researchers, the GC

provides a more accurate way to

could improve identification of patients

identify patients who may experience

who may benefit from more aggressive

recurrence of high-risk bladder cancer

treatment, such as adjuvant chemo-

following cystectomy, according to a

therapy. “Identification of candidates

new study.

at highest risk for recurrence who may

Using whole transcriptome profiling

need adjuvant therapy is currently

on 225 patients who underwent radical

based on clinical criteria that may

cystectomy for muscle-invasive bladder

not reflect the entire biology of the

cancer, Anirban P. Mitra, MD, PhD, of the

disease,” the authors wrote.

Center for Personalized Medicine at the

“We expect this study to provide

University of Southern California in Los

better understanding of the molecular

Angeles, and collaborators identified 15

alterations associated with aggressive

markers that could robustly and repro-

bladder cancer, and how one can man-

ducibly predict disease recurrence. This

age individual patients based on their

15-feature “genomic classifier” (GC),

genomic profiles,” Dr. Mitra told Renal &

which was independently validated on

Urology News.

341 patients, surpassed the prognostic

The study was a joint effort led

potential of standard clinical variables

by investigators at the University of

and previously reported genomic

Southern California in collaboration

signatures for muscle-invasive bladder

with the University of British Columbia

cancer, the researchers reported online

in Vancouver, Stanford University in

ahead of print in the Journal of the

Palo Alto, Calif., and a Vancouver-based

National Cancer Institute.

company. n

News_029_RUN1214.indd 29

treatment with XTANDI. Animal Data In an embryo-fetal developmental toxicity study in mice, enzalutamide caused developmental toxicity when administered at oral doses of 10 or 30 mg/kg/day throughout the period of organogenesis (gestational days 6-15). Findings included embryo-fetal lethality (increased post-implantation loss and resorptions) and decreased anogenital distance at ≥ 10 mg/kg/day,and cleft palate and absent palatine bone at 30 mg/kg/ day. Doses of 30 mg/kg/day caused maternal toxicity.

The doses tested in mice (1, 10 and 30 mg/kg/day) resulted in systemic exposures (AUC) approximately 0.04, 0.4 and 1.1 times, respectively, the exposures in patients. Enzalutamide did not cause developmental toxicity in rabbits when administered throughout the period of organogenesis (gestational days 6-18) at dose levels up to 10 mg/kg/day (approximately 0.4 times the exposures in patients based on AUC).

Nursing Mothers XTANDI is not indicated for use in women. It is not known if enzalutamide is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from XTANDI, a decision should be made to either discontinue nursing, or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use Safety and effectiveness of XTANDI in pediatric patients have not been established.

Geriatric Use Of 1671 patients who received XTANDI in the two randomized clinical trials, 75% were 65 and over, while 31% were 75 and over. No overall differences in safety or effectiveness were observed between these patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Patients with Renal Impairment A dedicated renal impairment trial for XTANDI has not been conducted.

Based on the population pharmacokinetic analysis using data from clinical trials in patients with metastatic CRPC and healthy volunteers, no significant difference in enzalutamide clearance was observed in patients with pre-existing mild to moderate renal impairment (30 mL/min ≤ creatinine clearance [CrCL] ≤ 89 mL/min) compared to patients and volunteers with baseline normal renal function (CrCL ≥ 90 mL/min). No initial dosage adjustment is necessary for patients with mild to moderate renal impairment. Severe renal impairment (CrCL < 30 mL/min) and end-stage renal disease have not been assessed [see Clinical Pharmacology (12.3)].

Patients with Hepatic Impairment A dedicated hepatic impairment trial compared the composite systemic exposure of enzalutamide plus N-desmethyl enzalutamide in volunteers with baseline mild or moderate hepatic impairment (Child-Pugh Class A and B, respectively) versus healthy controls with normal hepatic function. The composite AUC of enzalutamide plus N-desmethyl enzalutamide was similar in volunteers with mild or moderate baseline hepatic impairment compared to volunteers with normal hepatic function. No initial dosage adjustment is necessary for patients with baseline mild or moderate hepatic impairment. Baseline severe hepatic impairment (Child-Pugh Class C) has not been assessed [see Clinical Pharmacology (12.3)].

OVERDOSAGE In the event of an overdose, stop treatment with XTANDI and initiate general supportive measures taking into consideration the half-life of 5.8 days. In a dose escalation study, no seizures were reported at < 240 mg daily, whereas 3 seizures were reported, 1 each at 360 mg, 480 mg, and 600 mg daily.

Patients may be at increased risk of seizure following an overdose.

NONCLINICAL TOXICOLOGY Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term animal studies have not been conducted to evaluate the carcinogenic potential of enzalutamide.

Enzalutamide did not induce mutations in the bacterial reverse mutation (Ames) assay and was not genotoxic in either the in vitro mouse lymphoma thymidine kinase (Tk) gene mutation assay or the in vivo mouse micronucleus assay.

Based on nonclinical findings in repeat-dose toxicology studies, which were consistent with the pharmacological activity of enzalutamide, male fertility may be impaired by treatment with XTANDI. In a 26-week study in rats, atrophy of the prostate and seminal vesicles was observed at ≥ 30 mg/kg/day (equal to the human exposure based on AUC).

In 4-, 13-, and 39-week studies in dogs, hypospermatogenesis and atrophy of the prostate and epididymides were observed at ≥ 4 mg/kg/day

Renal & Urology News 29

(0.3 times the human exposure based on AUC).

Manufactured by: Catalent Pharma Solutions, LLC, St. Petersburg, FL 33716 Manufactured for and Distributed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Marketed by: Astellas Pharma US, Inc., Northbrook, IL 60062 Medivation, Inc., San Francisco, CA 94105 Revised: September 2014 14B006-XTA-BRFS Rx Only © 2014 Astellas Pharma US, Inc. XTANDI® is a registered trademark of Astellas Pharma Inc.

076-0516-PM

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