Uric Acid-Lowering Therapy May Increase CKD Risk

Uric Acid-Lowering May Raise CKD Risk

Findings do not support initiating this therapy to prevent development of chronic kidney disease

URIC ACID-LOWERING therapy is associated with a higher risk for newonset chronic kidney disease (CKD) among patients with baseline serum uric acid levels of 8 mg/d or less, a new study finds. The therapy did not change the risk for individuals with higher baseline serum uric acid levels.

“These findings do not support the initiation of uric acid-lowering therapy as a means to prevent the development of CKD,” investigators concluded.

Among 269,651 patients (94% male) with a baseline estimated glomerular filtration rate (eGFR) of at least 60 mL/ min/1.73 m2 and no albuminuria treated at US Veterans Affairs health care facilities from 2004 to 2019, a total of 29,501 patients (10.9%) started uric acid-lowering therapy. The vast majority (99.7%) received allopurinol. Of the full cohort, 21.7% eventually experienced an eGFR decline to less than 60 mL/min/1.73 m2 , 25.5% new-onset albuminuria, and 0.2% end-stage kidney disease (ESKD). After propensity-score matching, use vs nonuse of uric acid-lowering therapy was associated with a significant 15% higher risk of eGFR decline to less

than 60 mL/min/1.73 m2 and a significant 5% higher risk of albuminuria in the overall cohort, Csaba P. Kovesdy, MD, of Memphis VA Medical Center in Tennessee, and colleagues reported in JAMA Network Open. Allopurinol use did not decrease the risk for ESKD.

Among individuals with baseline serum uric acid levels of 8 mg/dL or less, uric acid-lowering therapy was significantly associated with 24% and 7% increased risks for an eGFR less than 60 mL/min/1.73 m2 and albuminuria, respectively. The investigators did not find these associations among those with higher baseline serum uric acid levels.

“Our findings of higher risk of incident CKD and albuminuria in patients with less severe elevations of serum uric concentration treated with urate lowering therapy may appear surprising, as we hypothesized that the lowering of uric acid levels would be beneficial owing to the detrimental effects of uric acid on various metabolic and cardiovascular processes,” the authors wrote.

They also noted that the findings “support results of recent large randomized clinical trials that found no benefit of allopurinol in delaying progression of established CKD.”

Dr Kovesdy’s team said their study “is notable for its large size, national representativeness, and availability of comprehensive information on a broad array of clinical data.” They also acknowledged that their study was observational and retrospective, and thus open to confounding. “While we accounted for major known confounders of the development of kidney disease, residual confounding remains possible, such as the doses of various potentially nephrotoxic medications or the severity of cardiovascular disease or other comorbidities.” In addition, their analysis included mostly male US veterans, so it is unclear whether their results apply to women or nonveterans, they noted. ■

Higher risk observed in patients with uric acid levels of 8 mg/dL or less at baseline.

Dysnatremias in ESKD Linked to Higher In-Hospital Mortality

HYPERNATREMIA AND hyponatremia in hospitalized patients with end-stage kidney disease (ESKD) are associated with higher in-hospital mortality and longer hospital length of stay (LOS), investigators concluded in a poster presented at the National Kidney Foundation’s 2022 Spring Clinical Meeting in Boston.

After adjusting for age, sex, race, and comorbidities, hypernatremia and hyponatremia were significantly associated with a 2.0- and 1.8-fold increased risk for in-hospital death compared with patients without these conditions, Calvin Ghimire, MD, of McLarin Flint Hospital in Flint, Michigan, and colleagues reported. Female patients had significantly lower in-hospital mortality and shorter LOS compared with male patients.

Patients with hypernatremia and hyponatremia had a significantly longer LOS than patients without these conditions (11.6 vs 5.7 days and 8.9 vs 5.4 days, respectively).

The findings are from a study of 643,555 index hospitalizations for ESKD identified in the National Inpatient Sample. The racial composition was 39.2% White and 34.9% Black. The study population was 54.72% male and 45.28% female.

Compared with patients who did not have hypernatremia, those with the condition were significantly older (66.5 vs 61.5 years) and significantly more likely to be Black (38.1% vs 34.8%).

Compared with patients who did not have hyponatremia, patients with hyponatremia were significantly older (63 vs 61 years), significantly more likely to be female (49.1% vs. 44.8%), and significantly less likely to be Black (27.2% vs 35.9%).

“Prevention of dysnatremia remains vital and patient education remains a cornerstone to achieve it,” Dr Ghimire’s team wrote.

They also observed, “Effectiveness of managing underlying comorbidities and renal replacement methods to maintain normal sodium level as per the requirement remains an unsolved mystery to prevent worse clinical outcomes and mortality.” ■

Endometrial CA Ups Risk for UTI, CKD

WOMEN WITH endometrial cancer are at increased risk for urinary problems, including lower urinary tract infection (UTI) and chronic kidney disease (CKD), according to a recent study.

An analysis of 265,605 women aged 66 years or older showed that women diagnosed with endometrial cancer had a 2.36-fold increased risk for lower UTI compared with women who did not have a history of cancer, Chelsea Anderson, PhD, MPH, of the Gillings School of Global Public Health at the University of North Carolina in Chapel Hill, and colleagues reported in Cancer Epidemiology, Biomarkers, & Prevention. They also had a 1.85- and 2.28-fold increased risk for CKD and kidney failure, respectively, and a 2.22fold increased risk for urinary stones.

“Results of the current study suggest that older women with endometrial cancer have a higher risk of several urinary outcomes than similarly aged women without a cancer history,” the authors wrote. “Timely identification and treatment of these conditions, especially among those with preexisting risk factors and those treated with chemotherapy and/or radiation, may be an important part of ongoing survivorship care after endometrial cancer.”

The study population, which investigators identified using the Surveillance, Epidemiology, and End ResultsMedicare linked database (2004-2017), compared 44,386 women diagnosed with endometrial cancer with a control group of 221,219 women without a cancer history matched by age, race or ethnicity, and state of residence.

In the endometrial cancer cohort, 65% of women had localized disease.

Among women with endometrial cancer, the risk of most urinary outcomes tended to be higher among women who were older at cancer diagnosis, according to the investigators. For example, compared with women aged 66-69 years, those aged 70-74, 75-79, 80-84, and 85 years or older had a significant 1.06-, 1.25-, 1.42-, and 1.51-fold increased risk for lower UTI, respectively, and 1.22-, 1.47-, 1.82-, and 2.10fold increased risk for CKD, respectively, Dr Anderson’s team reported.

The study identified racial and ethnic differences among women with endometrial cancer. For example, compared with White women, Black women had a 1.58- and 1.72-fold higher risk for CKD and renal failure, respectively, and Hispanic women had a 1.17-fold higher risk for lower UTIs. ■

COVID-19 Conversations With Older CKD Patients Inadequate

Limited discussions about vulnerability and advance care planning reported

CLINICIANS SHOULD make a greater effort to engage older patients with chronic kidney disease (CKD) in discussions about the risks they face from COVID-19 and the effect of the illness on treatment options, researchers concluded in an article in the Clinical Journal of the American Society of Nephrology.

The investigators based that conclusion on interviews with 39 patients aged 70 years or older with advanced CKD, 17 care partners, and 20 clinicians from Boston, Portland, Maine, San Diego, and Chicago from August to December 2020.

“Although clinicians perceived greater vulnerability among older patients CKD and more readily encouraged homebased modalities during the COVID-19 pandemic, their discussions of vulnerability, advance care planning, and conservative management remained limited, suggesting areas for improvement,” Thalia Porteny, PhD, MSc, a postdoctoral scholar at the REACH Lab at Tufts University in Medford, Massachusetts, and colleagues concluded.

The investigators found that many patients “learned about their high vulnerability to COVID-19 from the media, and some expressed that they would have preferred to discuss their heightened risk with clinicians.”

Unanswered Questions “I think the most surprising finding was that few clinicians directly discussed how COVID reshaped risks for patients with CKD, and patients had unanswered questions about COVID and the impacts on their kidney disease,” study investigator Keren Ladin, PhD, MSc, an associate professor at Tufts and director of the REACH Lab, said in an interview with Renal & Urology News.

She also observed, “The findings illustrate that patients are generally satisfied with treatment decisions and perceive them to be quite safe, irrespective of whether they selected in-center or a home-based treatment. Undoubtedly, this reflects the tremendous efforts of kidney clinicians to adapt to higher precautions in the clinic and dialysis center, and communication with patients about the efforts in place to keep them safe.”

Adapting decision-making and treatment recommendations to reflect new understanding of COVID-19-related risks offers patients the opportunity to better understand and weigh the risks and benefits, Dr Ladin said.

Favorable View of Telemedicine The interviews also revealed a generally favorable view of telemedicine. “As we think about the future, our findings suggest an openness to telemedicine, as participants perceived this form of care to be convenient; it also gave care partners the ability to participate in clinical encounters when in-person care was restricted,” the authors wrote.

Clinicians are well positioned to discuss challenging new risks with patients, even under conditions of significant uncertainty and emerging information, she noted. Nephrologists can be more open to recommending home-based modalities, especially when risks of in-center modalities increase. “Although this was true for peritoneal dialysis, clinicians were still hesitant to recommend or discuss conservative management. This offers an important opportunity for improvement, as a balanced description of treatment options, including discussion of risks, benefits, and implications for quality of life is critical to shared decision-making,” Dr Ladin said.

Nephrologist Alexander Chang, MD, an assistant professor of clinical research and co-director of the Kidney Health Research Institute at Geisinger Medical Center in Danville, Pennsylvania, said his team has been discussing these issues at length over the past year. “I’ve noticed myself that the pandemic was an effective way to introduce the topic of home dialysis modalities to my patients, with some success in getting them to consider home modalities as the first option if possible,” Dr Chang said.

He said he agrees that the pandemic may have encouraged clinicians and patients to think more about home dialysis modalities, but the true impact remains unclear. “The burnout issue and the ‘great resignation’ with staffing challenges may have also limited the ability of providers in getting patients on home dialysis, as that requires experienced dialysis nurses available to educate and train patients as well as availability of surgeons familiar with peritoneal dialysis and operating room time during the pandemic,” Dr Chang said.

Panduranga Rao, MBBS, Richard D Swartz Collegiate Professor of Nephrology at the University of Michigan in Ann Arbor, said he predicts an increase in the use of home dialysis, perhaps peritoneal dialysis more so than home hemodialysis, in coming years due to a confluence of factors.

“We could be seeing a new era in home dialysis, especially given the innovations in dialysis hardware which would make it more appealing, less intimidating and less burdensome even to the elderly patient,” Dr Rao said. ■

Race Affects ADPKD Care, Study Finds

INVESTIGATORS HAVE identified racial and ethnic disparities in autosomal dominant polycystic kidney disease (ADPKD) outcomes.

“Compared with White patients, Black and Hispanic patients with ADPKD have earlier age of onset of kidney failure and less access to kidney transplantation,” Rita L. McGill, MD, of the University of Chicago in Illinois and colleagues concluded in a paper published in the Clinical Journal of the American Society of Nephrology. National and local resources need to focus on education and outreach, and they need to clarify these systemic disadvantages to achieve health equity for all patients.

Among 41,485 adults aged 30 years or older with ADPKD in the 20002018 US Renal Data System, 77% were White, 13% were Black, and 10% were Hispanic. Black and Hispanic patients experienced kidney failure at significantly younger ages than White patients (55 and 53 years vs 57 years), Dr McGill’s team reported. Yet, in adjusted analyses, Black and Hispanic patients had significant 67% and 50% decreased odds of preemptive kidney transplantation and 39% and 22% decreased odds of transplantation after dialysis initiation, respectively, compared with White patients. Living donor transplants occurred in just 7% and 15% of Black and Hispanic patients compared with 27% of White patients.

Results showed 20% and 22% of Black and Hispanic patients were placed on a transplant waiting list prior to kidney failure, respectively, compared with 38% of White patients. The median time from waitlisting to transplantation was 28 and 24 months for Black and Hispanic patients, respectively, compared with 15 months for White patients.

Nephrology care prior to kidney failure, private insurance, employment, and higher income increased the odds of both preemptive transplantation and transplantation after dialysis initiation, the investigators reported. ■