Diabetes May Complicate Renal Biopsy

Recent study reveals an increased risk for major bleeding complications and need for transfusion

THE RISK FOR MAJOR bleeding complications after percutaneous renal biopsy is higher among patients with than without diabetes, according to a new Japanese study.

All percutaneous renal biopsies in Japan are performed in the hospital. In a nationwide inpatient database of 76,302 Japanese patients who underwent percutaneous renal biopsy, major bleeding complications occurred in 678 patients (0.9%), including 622 (0.8%) with red blood cell (RBC) transfusion within 7 days and 109 (0.1%) with invasive hemostasis requiring transcatheter arterial embolization or nephrectomy. Of the cohort, 8245 had diabetes mellitus.

Major bleeding complications (3.1% vs 0.6%), including requiring RBC transfusion (2.9% vs 0.66%), transfusion of more than 1 L (1.6% vs 0.1%), and invasive hemostasis (0.3% vs 0.1%) was significantly more common in the group with vs without diabetes. In multivariate analysis, the diabetes group had a 2.4-fold increased risk for major

bleeding complications and a 2.4- and 1.9-fold increased risk for transfusion and invasive hemostasis, respectively, corresponding author Hideo Yasunaga, PhD, of The University of Tokyo in Japan, and colleagues reported in Kidney International Reports. Multiagent or insulin for diabetes treatment was significantly associated with a 1.6-fold increased risk for major bleeding complications compared with single-agent treatment.

The patients with diabetes tended to be older, male, and steroid users with acute kidney injury (AKI), chronic kidney disease (CKD), or rapidly progressing glomerulonephritis (RPGN). In multivariable analysis, older age, female sex, AKI, CKD, or RPGN, and steroid use each were associated with higher risks of major bleeding. Diabetes remained a risk factor after adjustment for patient and hospital characteristics and in a sensitivity analysis considering anemia, according to the investigators.

Dr Yasunaga’s team acknowledged that the study was limited by a lack of information on needle gauge, glucose control, timing of discontinuation and resumption of antithrombotic agents, and some other relevant factors.

The researchers concluded that “nephrologists should carefully judge whether the anticipated benefits outweigh the relatively high risk of major bleeding complications when considering [percutaneous renal biopsy] for patients with diabetes.”

In an accompanying editorial, Emilio D. Poggio, MD, of Glickman Urological and Kidney Institute at Cleveland Clinic in Cleveland, Ohio, and colleagues wrote that they “strongly support the practice of [percutaneous renal biopsy] in patients with diabetes when a secondary diagnosis is suspected, and identification of that disease would alter management with the hopes of reducing the progression to end-stage kidney disease. As in all patients with or without diabetic kidney disease, we recommend aggressively managing modifiable risk factors to reduce the risk of bleeding.” ■

Researchers report results from their study of 76,302 Japanese patients.

Cardiovascular Calcification Increases Death Risk in ESKD

CALCIFICATION IN cardiac valves and aorta portends worse survival and progresses faster in patients with endstage kidney disease (ESKD), according to a recent study.

In a study of 434 patients receiving hemodialysis (HD), 27.2% of patients displayed mitral valve calcification (MVC) and 31.8% aortic valve calcification (AVC) on echocardiography. The group with vs without cardiovascular calcification had significantly higher all-cause and cardiovascular mortality rates, Ning Cao, MD, of General Hospital of Northern Theater Command, Liaoning, China, and colleagues reported in BMC Nephrology. The presence of MVC and AVC was significantly associated with 1.5- and 1.4-fold increased risks for all-cause mortality and 2.3- and 2.4-fold increased risks for cardiovascular mortality, respectively. Left atrial dimension also significantly correlated with all-cause and cardiovascular death.

Cardiovascular calcification on routine echocardiography “should not be overlooked and can be used for risk assessment in maintenance HD patients,” Dr Cao and colleagues wrote. “Moreover, it can help identify patients who are appropriate for intensive medical treatment to reduce cardiovascular events.”

In a second study, researchers examined progression of aortic calcification in 150 patients with stage 4-5 chronic kidney disease transitioning to dialysis or transplantation or continuing conservative care. The median abdominal aortic calcification (AAC) score significantly increased from 4.8 before renal replacement therapy or conservative care to 8.0 at 3 years after the transition, with no difference among treatment modalities, Roosa Lankinen, MD, of University of Turku, Finland, and colleagues reported in Kidney and Blood Pressure Research.

The annual rate of AAC increase was significantly associated with a 1.4-fold higher risk for mortality and, in transplant recipients, a longer time on the transplant waiting list. ■

Study Finds Continuous Rise in mPCa

METASTATIC PROSTATE cancer (mPCa) incidence continues to increase in the US, a trend temporally associated with changes in guidelines from the US Preventive Services Task Force (USPSTF), according to the latest data.

The USPSTF recommended against routine PSA screening of men older than 75 years in 2008 and all men in 2012, but revised their recommendation in 2018, advising personalized decision-making for screening men aged 55 to 69 years.

Investigators observed the trend when they analyzed data from 836,282 PCa cases in the Surveillance, Epidemiology, and End Results (SEER) 18 registry. They identified 26,642 men (56.5%) aged 45 to 74 years and 20,507 (43.5%) men aged 75 years or older diagnosed with metastatic PCa from 2004 through 2018.

Among men aged 45 to 74 years, mPCa incidence was stable from 2004 to 2010 (-0.4% annually), but significantly increased 5.3% annually from 2010 to 2018, Mihir M. Desai, MD, MPH, of the University of Southern California’s Keck School of Medicine in Los Angeles, and colleagues reported in JAMA Network Open. Among men aged 75 years or older, mPCa incidence significantly decreased 1.5% annually from 2004 to 2011, but significantly increased 6.5% annually from 2011 to 2018.

The rise in mPCa occurred despite a significant concurrent reduction in overall PCa diagnoses, according to the investigators.

“Although the reasons behind this recent rising incidence of mPCa are multifactorial, it is unlikely to be due to a true change in cancer biology in such a short period,” the authors wrote. “Factors such as environmental exposures or germline variations leading to changes in epidemiological signatures of cancers take substantially longer. Rather, changes in clinical policy and/ or practice such as screening strategies and use of diagnostic imaging are much more likely to explain such short-term changes in cancer epidemiological trends.”

Regardless of the cause, Dr Desai and colleagues noted, the finding of a rising incidence of mPCa by itself does not imply that screening practices should be changed. “The overall risk vs benefit of PSA-based screening is extremely complex and must take into account various other factors that impact the overall health of the community.” ■

Anaphylaxis Risk With IV Iron Differs By Product

BY NATASHA PERSAUD INTRAVENOUS (IV) iron use overall is associated with a very low risk for anaphylaxis, but iron dextran and ferumoxytol are associated with a higher risk compared with iron sucrose, according to new research.

Investigators compared the risks for anaphylaxis among 5 IV iron products using data from 167,925 new users of IV iron older than 65 years receiving Medicare Part D. The adjusted rates for anaphylaxis per 10,000 administrations were 9.8 cases for iron dextran, 4.0 cases for ferumoxytol, 1.5 cases for ferric gluconate, 1.2 cases for iron sucrose, and 0.8 cases for ferric carboxymaltose.

Compared with iron sucrose, iron dextran and ferumoxytol were significantly associated with 8.3- and 3.4-fold increased odds for anaphylaxis, respectively, Chintan V. Dave, PharmD, PhD, of Rutgers University, New Brunswick, New Jersey, and colleagues reported in the Annals of Internal Medicine. Hospitalization for anaphylactic reactions occurred only among patients receiving iron dextran or ferumoxytol. Anaphylaxis with CPR, hypotension, or epinephrine also occurred at higher rates among patients receiving iron dextran or ferumoxytol.

High-molecular-weight iron dextran was withdrawn from the US market in 2014. Anaphylaxis risk with low-molecular-weight iron dextran was also increased.

“Clinically, factors guiding the choice of parenteral iron preparation should include not only the risk for anaphylaxis but also medical history, clinical indication, setting, dose, number and duration of administrations needed, risk for other adverse events, and cost,” Dr Dave’s team wrote.

In a second study of 12,237 patients (mean age 51 years) with iron deficiency published in JAMA Network Open, Joseph Shatzel, MD, of OHSU Knight Cancer Institute, Portland, Oregon, and colleagues found a low 3.9% rate of adverse events from IV iron use. The adverse event rate was significantly higher among patients who received premedication such as corticosteroids and antihistamines compared with those who did not (38.6% vs 1.7%). Severe adverse reactions were extremely rare. The study identified only 2 documented epinephrine administrations, both associated with iron dextran use, according to the investigators.

The risk for infusion reactions differed significantly among IV iron products: 4.3% with iron sucrose, 3.8% with iron dextran, 1.8% with ferumoxytol, and 1.4% with ferric carboxymaltose. Among patients with a history of infusion reactions, readministration with the same IV iron formulation was significantly associated with a higher reaction rate especially with (68%) than without (32%) premedication, compared with an alternate IV iron formulation with (21%) than without (5%) premedication.

“Although further investigation is warranted to determine the ideal approach of readministration of iron in those who experience an infusion reaction,” the investigators concluded, “our data suggests that rechallenging patients with IV iron, perhaps with an alternate formulation and not preceded by sedating antihistamines, would be both safe and effective. Overall, IV iron continues to hold an undeniably essential role in the management of iron deficiency.” ■

Pediatric ESKD Racial Gap Persists Into Adulthood

BY NATASHA PERSAUD A 30-YEAR observational cohort study of children with childhood-onset kidney failure found that Black patients are disadvantaged in all aspects of kidney transplantation into adulthood compared with White patients, according to investigators.

Black patients have a significantly higher overall mortality rate and lower graft survival rate compared with White patients. Black patients also are less likely to undergo preemptive transplantation. Researchers speculate that socioeconomic factors might contribute to the disparities.

“Our analysis demonstrated that Black patients faced more economic challenges as evidenced by a greater likelihood of living in areas of low median household income, having Medicaid as primary payer, or having no health insurance, all of which could present barriers to transplant access and limit the chance of preemptive transplantation,” they wrote.

Using 1980-2017 US Renal Data System (USRDS) data, Susan R. Mendley, MD, and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of

ESKD race disparities

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Health in Bethesda, Maryland, studied 28,337 children — 24% Black and 76% White — diagnosed with ESKD before age 18 years.

Compared with White patients, Black patients had a significantly lower unadjusted 30-year overall survival rate (39% vs 57%) and significantly lower rate of preemptive transplantation (23.6% vs 13.4%), the investigators reported in the Journal of the American Society of Nephrology.

Compared with White patients, Black patients had a significant 45% higher risk for all-cause mortality, a 31% lower rate of first transplant, and a 39% lower rate of second transplant, Dr Mendley’s team reported. A significantly lower proportion of Black patients had a living donor for a first (26.0% vs 49.2%) or second kidney transplant (15.4% vs 35.1%).

After their first transplant, Black patients received 11% fewer total lifetime transplants compared with White patients, according to the investigators. A significantly higher proportion of Black than White patients never received a transplant (23.6% vs 13.4%).

Among transplanted patients, graft survival was shorter in Black than White patients (median 6.1 vs 10.3 years). Graft survival was 20% and 24% lower after the first and second transplant, respectively, for the Black population.

The risk for mortality was 38% and 23% higher after the first and second transplant, respectively, for Black patients, the investigators reported. These trends largely persisted across defined eras from 1980 through 2017 with no meaningful improvement in outcomes

over time despite medical and technical advancements. The investigators could not assess how 2014 changes in the Kidney Allocation System may have affected outcomes.

Transplantation was associated with a 72% decreased risk for death over a lifetime for patients with childhood-onset ESKD, Dr Mendley and colleagues reported. Yet time with a functioning allograft was significantly shorter for Black than White patients who began renal replacement therapy in childhood: 57% vs 83% of follow-up time, respectively.

In a simulation, investigators found that equalizing transplant number, graft survival, and time with a functioning transplant would reduce Black excess mortality from 45% to 34%.

“This indicates that 35% of the excess mortality between Black and White patients would be eliminated if the transplant experience was the same in each racial group, but 65% of the survival differential would remain from other mediators independent of transplantation,” Dr Mendley’s team wrote. Transplant waiting time, graft survival, and access to subsequent transplants may all contribute to the disparity in time with a functioning graft, the investigators noted. They suggested that social determinants of health and the consequences of structural racism likely play important roles. A greater proportion of the Black than White population had a low median household income of less than $34,000 (56.2% vs 11.1%) and Medicaid as primary insurance (48.3% vs 32.9%). The study lacked more granular information on socioeconomic status, comorbidities, and body mass index, limiting interpretation of the findings. ■

HRQOL Predicts Post-RP Outcomes in High-Risk PCa

MEN WITH GOOD health-related quality of life are more likely to have favorable outcomes following radical prostatectomy (RP) for high-risk prostate cancer, researchers reported at the 2022 Genitourinary Cancers Symposium.

In a propensity-score matched analysis of 636 patients with high-risk prostate cancer, the biochemical recurrence-free survival rate at 5 years was significantly higher among those who had a preoperative global health status (GHS) of 70 or higher vs lower than 70 on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQC30), Thilo Westhofen, MD, of LudwigMaximilians-University Munich in Germany reported on behalf of his team. The metastasis-free survival rate at 5 years was also significantly higher among patients with a good GHS at baseline: 86% vs 68%, respectively. The groups were well matched by age, PSA, pT stage, Gleason grade, positive surgical margin rate, and lymph node involvement. A multivariate analysis confirmed that a GHS of 70 or more independently predicted a 40% and 49% decreased risk for biochemical recurrence and metastasis, respectively, according to researchers. ■