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Grand RoundsWeekly Evidence Brief

Nephrology

Edition

30-Second Takeaway

  • Febuxostat did not improve kidney, cardiovascular, or mortality outcomes in stage 3–4 CKD with asymptomatic hyperuricemia.
  • Oral semaglutide slowed eGFR loss but did not significantly reduce composite kidney endpoints in high-risk type 2 diabetes.
  • Finerenone reduced albuminuria without improving arterial stiffness, supporting intraglomerular rather than macrovascular mechanisms.

Week ending December 13, 2025

Targeted therapies in CKD and glomerular disease: separating mechanistic promise from clinical payoff

Febuxostat provides no kidney or survival benefit in asymptomatic hyperuricemic stage 3–4 CKD

AMERICAN JOURNAL OF NEPHROLOGYDec 12, 2025

In 3,232 adults with newly diagnosed stage 3–4 CKD and asymptomatic hyperuricemia, 20% initiated febuxostat within one year of hyperuricemia detection. Over five years, febuxostat initiation did not reduce the composite of ≥40% eGFR decline, ESKD, or kidney replacement therapy (HR 1.07; 95% CI 0.91–1.20). All-cause mortality (HR 1.00; 95% CI 0.66–1.35) and MACE (HR 1.03; 95% CI 0.95–1.11) were also unaffected. These findings argue against initiating febuxostat solely for kidney protection in asymptomatic hyperuricemic stage 3–4 CKD patients.

SOUL: oral semaglutide slows eGFR decline without reducing kidney event composites

DIABETES CAREDec 11, 2025

In SOUL, 9,650 people with type 2 diabetes and ASCVD and/or CKD were randomized to oral semaglutide or placebo for 47.5 months. Semaglutide did not significantly reduce the five-point kidney composite versus placebo (8.4% vs. 9.0%; HR 0.91; 95% CI 0.80–1.05). The four-point composite excluding cardiovascular death was also nonsignificant (HR 0.86; 95% CI 0.66–1.10). However, annual eGFR decline was slower with semaglutide (−1.67 vs. −2.06 mL/min/1.73 m²; difference 0.40; 95% CI 0.27–0.53).

FIVE-STAR: finerenone cuts albuminuria but not arterial stiffness in diabetic CKD

CARDIOVASCULAR DIABETOLOGYDec 6, 2025

FIVE-STAR randomized 101 Japanese patients with type 2 diabetes, eGFR 25–<90, and UACR 30–<3500 mg/g to finerenone or placebo. At 24 weeks, changes in cardio-ankle vascular index were similar (group difference −0.057; 95% CI −0.428 to 0.314; P = 0.760), indicating no arterial stiffness effect. Finerenone reduced UACR by ~29% at weeks 12 and 24 versus placebo, demonstrating sustained antiproteinuric action. An early, persistent eGFR drop occurred without increases in urinary tubular injury markers, suggesting hemodynamic rather than nephrotoxic effects.

References

Numbered in order of appearance. Click any reference to view details.

Additional Reads

Optional additional studies from this edition.

Edition context

Clinical signal

  • Routine febuxostat for asymptomatic hyperuricemia in CKD lacks outcome benefit and should not be used for renoprotection alone.
  • When selecting GLP-1 RAs for diabetic CKD, oral semaglutide offers cardiovascular benefit and modest eGFR preservation, but limited kidney hard-endpoint data.
  • Finerenone’s renal effects in diabetic CKD appear driven by hemodynamic and intraglomerular pressure changes, not large-artery stiffness remodeling.