New research was presented at Kidney Week 2022, the American Society of Nephrology annual meeting, from November 3-6. The features below highlight some of the studies that emerged from the conference.

Stopping RAS Inhibitors in Advanced CKD Not Linked With eGFR Changes

Although renin-angiotensin system (RAS) inhibitors slow the progression of mild or moderate CKD, some past studies have indicated that cessation of RAS inhibitors in patients with advanced CKD may increase eGFR or slow its decline, according to Sunil Bhandari, MBCHD, MRCP, FRCP, PhD, MClinEdu. Dr. Bhandari and colleagues sought to determine the eGFR at 3 years and the development of ESKD in a multicenter, open-label trial, where patients with advanced and progressive CKD (eGFR, <30 mL per minute per 1.73 m2 of body surface area) were randomly assigned either to continued therapy with RAS inhibitors or discontinuation of it. Prespecified subgroups were defined based on age, proteinuria, eGFR, type of diabetes, and mean arterial pressure. The discontinuation of RAS inhibitors was not linked with a considerable difference in the long-term rate of decrease in eGFR among patients with advanced and progressive CDK. Among 411 patients after 3 years, the least-squares mean eGFR was 13.3±0.6 mL per minute per 1.73 m2 in the continuation group and 12.6±0.7 mL per minute per 1.73 m2 in the discontinuation group and (difference, −0.7; 95% CI, −2.5 to 1.0), with a negative value favoring the outcome in the continuation group. ESKD, or the initiation of renal replacement therapy, occurred in 56% in the continuation group
and 62% in the discontinuation group (HR, 1.28; 95% CI, 0.99-1.65).

Kidney Donors Who Develop AKI Tend to be Older Males With Comorbidities

An increasing need for kidney transplantation, particularly from living donors, has resulted in the need for a better understanding of risks associated with kidney donation. Mistafa Hafid, MD, and colleagues compared the differences in characteristics in donors who developed acute kidney injury (AKI) within 1 year after donation with those who did not develop AKI. Researchers conducted a retrospective, multicenter cohort study of 42,955 adult donors from 59 United States healthcare organizations. They then identified individuals with a confirmed diagnosis of AKI within a year of donation and calculated the OR and 95% CI of diagnosis of ESRD and death in the first 5 years after donation. The study team found that 3,055 donors had a confirmed AKI diagnosis within the first year. Patients who developed AKI were older at the time of donation (44.2±13.5 vs 40.8±12.9; P<0.0001). They were also more likely to be male, have hypertension, nicotine dependence, and a BMI of greater than 30 kg/m2, and be on a diuretic. Furthermore, a total of 5,554 donors (1,874 with an AKI history) were diagnosed with ESRD and 1,266 donors
(501 with AKI) died within the first 5 years after donation. AKI was also linked with greater odds of ESRD (OR, 15.2; 95% CI, 14.1-16.5), and mortality (OR, 9.9; 95% CI, 8.8-11.2), after propensity matching.

Empagliflozin Protects At-Risk Patients from CKD Progression

To better understand the effects of empagliflozin in patients with CKD who are at risk for disease progression, William Herrington, MD, MBBS, and colleagues conducted a clinical trial to examine the impact of the treatment. “The effects of empagliflozin in patients with [CKD] who are at risk for disease progression are not well understood,” the study authors wrote. Patients with CKD who had an eGFR of at least 20 but less than 45 mL per minute per 1.73 m2 of body surface area, or who had an eGFR of at least 45 but less than 90 mL per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio of at least 200, were enrolled. A total of 6,609 patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. A composite of progression of kidney disease (defined as ESKD, a sustained decrease in eGFR to <10 mL per minute per 1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes was the primary outcome. During a median follow-up of 2 years, kidney disease progression or death from cardiovascular causes occurred in 13.1% of 3,304 patients in the empagliflozin group and in 16.9% of 3,305 patients in the placebo group (HR, 0.72; 95% CI, 0.64-0.82; P<0.001). In the empagliflozin group, the rate of hospitalization from any cause was lower than in the placebo group (HR, 0.86; 95% CI, 0.78-0.95; P=0.003), but there were no notable differences between the groups with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes
or death from any cause. The rates were similar in the two groups for serious adverse events.

No Evidence for Persistent/Progressive Kidney Disease After Non-Severe COVID-19

After non-severe COVID-19, a wide range of abnormal findings have been reported in patients, but little is known about kidney outcomes, according to Christian Schmidt-Lauber, PhD, and colleagues. To fill this knowledge gap, researchers aimed to assess relevant kidney outcomes after COVID-19 infection. They conducted a cross-sectional study of patients after non-severe COVID-19 (N=443) and matched controls without prior COVID-19 (N=1,328).
During the COVID-19 pandemic, the study recruited patients at least 4 months after a PCR test for SARS-CoV-2 infection. Patients aged 45-74 were matched by sex, age, and education. Albumin, eGFR, albuminuria, hematuria, pyuria, and Dickkopf-related protein 3 were the main outcomes. A median 9 months after SARS-CoV-2 infection, researchers observed that most patients had mild COVID-19; just 31 were hospitalized and none were treated in an ICU. Compared with the non-COVID-19 cohort, the risk for CKD, defined by an eGFR of less than 60 mL/ min/1.73m2 (OR, 0.9) or severely increased albuminuria (OR, 0.79), was not increased in the COVID-19 cohort. In early CKD stages, this also applied. In post-COVID patients, however, mean eGFR was mildly lower, even after adjusting for known risk factors (adjusted P=0.032). “We found no elevation of hematuria, pyuria, and proteinuria
for the post-COVID cohort, suggesting no systematic ongoing kidney involvement,” the study authors wrote.

Hyponatremia Linked With Probable Dementia & All-Cause Mortality

Although severe hyponatremia (hypoNa) requiring treatment with hypertonic saline has been linked with probable dementia (PD), it is unknown if mild hyponatremia raises the risk for mild cognitive impairment (MCI)/PD, according to Amara Sarwal, MD. Dr. Sarwal and colleagues conducted the Systolic Blood Pressure Intervention Trial (SPRINT) MIND study (N=8,561) to examine the impact of intensive systolic blood pressure (SBP) control (goal, <120 mmHg) versus standard SBP control (goal, <140 mmHg) on risk for adjudicated MCI/PD. In this post-hoc
secondary analysis, researchers included 8,541 SPRINT-MIND participants with baseline serum sodium (Na) greater than 130 meq/L and Non missing baseline and 6-month (6m) serum Na. Incident hypoNa was defined as a serum Na of less than 130 mmol/L at 6m and related incident hypoNa with time to MCI alone, PD alone, a composite of MCI/PD and all-cause mortality (ACM) in separate Cox regression models adjusted for the SBP intervention, gender, age, race, BMI, eGFR, smoking, cardiovascular disease, and congestive heart failure. A total of 129 (1.5%) participants developed incident hyponatremia at 6m with a mean serum sodium of 127±3 meq/L. Those with incident hyponatremia were mostly women, older, and Black, had lower BMI, were treated with thiazide diuretics, and assigned to an intensive SBP arm compared with those without incident hyponatremia. There were 324 ACM, 1,254 MCI, 1,485 MCI/PD, and 324 PD events.