Research presented at the European Renal Association Congress, held June 3-6 in Glasgow, Scotland, highlighted new findings in chronic kidney disease (CKD), including evidence supporting more precise GFR assessment and trial results on finerenone in nondiabetic CKD and rivaroxaban in advanced CKD patients with cardiovascular risk factors.

CKD Thresholds and Outcomes

Among nearly 6,200 Swedish adults in a retrospective observational study, researchers found that a measured glomerular filtration rate (mGFR) of 60 mL/min/1.73m², compared with 90 mL/min/1.73m², was associated with higher rates of all-cause mortality and kidney failure – supporting a 60 mL/min/1.73m² threshold to define CKD.

The study by Edouard L. Fu, PhD, et al., simultaneously published in JAMA, found these associations were best reflected in estimated glomerular filtration rate (eGFR) values calculated with both plasma creatinine and cystatin C (eGFRcr-cys).

Results at nearly six years showed that all-cause mortality was 21% higher (27.6 vs. 22.4 deaths per 1,000 person-years) in patients with an mGFR of 60 mL/min/1.73m² vs. 90 mL/min/1.73m², and kidney failure with replacement therapy was nearly threefold higher (1.2 vs. 0.4 per 1,000 person-years; hazard ratio [HR], 2.85), respectively.

While associations for eGFRcr-cys did not differ significantly from those for mGFR, researchers found that eGFRcr underestimated and eGFRcys overestimated associations with all-cause mortality.

"This finding adds to existing evidence that integrating these [two] biomarkers for eGFR more precisely reflects kidney function than equations that rely on creatinine or cystatin C alone," write Vishnu S. Potluri, MD, MPH, et al., in an accompanying editorial comment.

Finerenone in CKD

Finerenone led to a slower decrease in eGFR over 32 months in nearly 1,600 adults with nondiabetic CKD in the FIND-CKD trial, according to results simultaneously published by H.J.L. Heerspink, PhD, et al., in the NEJM.

Patients were randomized to finerenone 10 or 20 mg or placebo. The mean eGFR was 46.8 and 46.6 mL/min/1.73m² in the two groups, respectively, and median urinary albumin-to-creatine ratio was 818.9 mg/g.

In the finerenone and placebo groups, the mean annual rate of change in eGFR was –3.3 mL/min/1.73m² vs. –4.0 mL/min/1.73m²). Moreover, with finerenone there was a 23% lower risk of the composite outcome of ≥57% eGFR reduction from baseline, kidney failure, heart failure hospitalization and cardiovascular death (p=0.04). Reductions were also seen in a composite of two cardiovascular outcomes (HR, 0.60) and composite of two renal outcomes (HR, 0.78).

An exploratory analysis of FIND-CKD, by Brendon L. Neuen, MBBS, PhD, et al., simultaneously published in JAMA, found similar results in a subgroup of 903 participants with investigator-reported glomerular diseases (mean eGFR annual rate change, –3.50 mL/min/1.73m² with finerenone vs. –4.23 mL/min/1.73m² with placebo). Additionally, finerenone reduced albuminuria at one year by 42% and lowered the risk of kidney failure or eGFR reduction ≥40% by 26% (7.42 vs. 9.60 events per 100 person-years; HR, 0.74), with the effect consistent across glomerular disease subtypes.

No Risk Reduction With Rivaroxaban

In nearly 1,500 adults with advanced CKD and at least one cardiovascular risk factor, low-dose (2.5 mg) rivaroxaban did not reduce the risk of adverse cardiovascular events compared with placebo (13.0 vs. 11.8 events per 100 person-years; HR, 1.90; p=0.46), and researchers found a significantly higher risk of major bleeding (5.1 vs. 3.4 events per 100 person-years; HR, 1.51; p=0.04). The results of the international TRACK trial, led by Sunil V. Badve, PhD, et al., was simultaneously published in JAMA.

Of the 1,360 patients who completed follow-up over a median of 1.7 years, 23% of patients in the rivaroxaban group and 21% in the placebo group experienced the primary outcome – a composite of cardiovascular death, nonfatal myocardial infarction, stroke or peripheral artery disease event (13.0 vs. 11.8 events per 100 person-years; HR, 1.90; p=0.46).

Notably, the trial had a discontinuation rate of 28% and was stopped early for lack of efficacy.

"TRACK sets the direction for the questions that must be asked next, particularly regarding which patients are most likely to benefit (e.g., those with established cardiovascular disease) and whether alternative oral anticoagulation strategies may prove more effective or safer in selected CKD populations," write Nisha Bansal, MD, and Wolfgang C. Winkelmayer, MD, in an accompanying editorial comment.