Nephrology

Empagliflozin after severe AKI did not lower 1-year MAKE but reduced recurrent AKI

In this multicenter RCT, 200 survivors of predominantly stage 3 AKI were randomized to empagliflozin 10 mg daily or placebo for 1 year. Participants were dialysis-independent with eGFR ≥20 ml/min/1.73 m² at enrollment across three tertiary hospitals. The primary outcome, MAKE365, occurred in 35% with empagliflozin versus 36% with placebo (P = 0.82), showing no benefit on the composite. Empagliflozin halved recurrent AKI incidence (34 vs 66 episodes per 100 person-years; incident rate ratio 0.51; 95% CI 0.31-0.84; P = 0.008). 1

Urinary clusterin predicts DKD progression and response to atrasentan in SONAR

A nested proteomics case-control analysis within SONAR (N = 180) identified urinary clusterin (uCLU) as the top biomarker candidate for kidney outcomes. Transcriptomics of independent human kidney biopsies showed higher CLU mRNA associated with worse kidney function and outcomes. In the full SONAR population (N = 3,060), higher baseline uCLU predicted worse kidney outcomes. Atrasentan reduced uCLU by 42.6% over six weeks, and early uCLU reductions independently predicted improved kidney outcomes. 2

African-ancestry GWAS clarifies eGFR loci and polygenic risk performance

This three-stage GWAS meta-analysis combined ~26,000 continental Africans and ~81,000 African-ancestry individuals in the diaspora to study eGFR. Continental African meta-analysis identified four independent genome-wide significant loci, including two previously unreported loci. Pan-African meta-analysis identified 19 independent loci, including three novel loci, with fine-mapping implicating four loci with high causal probability. Phenome-wide analyses showed pleiotropic effects on cardiometabolic and immunologic traits, relevant for multisystem risk assessment. 3