Nephrology

Sibeprenlimab gains first approval for IgA nephropathy based on proteinuria reduction

Sibeprenlimab is a fully humanized monoclonal antibody targeting APRIL, now approved to reduce proteinuria in adults with primary IgA nephropathy at risk for progression. APRIL signaling is implicated in glomerular injury in IgA nephropathy, and sibeprenlimab suppresses circulating APRIL levels. Interim analyses from the ongoing phase III VISIONARY trial showed that sibeprenlimab treatment reduced proteinuria in IgA nephropathy patients. This regulatory review summarizes developmental milestones, mechanism, and key efficacy data supporting its first approval for IgA nephropathy management. 1

Monlunabant shows no significant albuminuria benefit in diabetic kidney disease

This phase 2 randomized, double-blind, placebo-controlled trial tested monlunabant 10 mg and 25 mg versus placebo for 16 weeks in adults with diabetic kidney disease. The primary endpoint, change in UACR at week 16, did not differ significantly between monlunabant 25 mg and placebo (ETR 0.72, 95% CI 0.46–1.14). Monlunabant 10 mg also showed no statistically significant albuminuria benefit versus placebo, and secondary endpoints for UPCR and eGFR were similarly neutral. Gastrointestinal adverse events, mainly nausea, vomiting, and diarrhea, were most frequent and withdrawal rates increased with higher monlunabant dose. The trial failed to establish proof of concept for CB1 inverse agonism in diabetic kidney disease, though large placebo effects complicate interpretation. 2

Folate lowers homocysteine in CKD without improving cardiovascular or mortality outcomes

This systematic review and meta-analysis included 37 trials with 8625 adults, almost all with chronic kidney disease, evaluating folate-based supplementation. Folate significantly reduced plasma homocysteine (MD −8.09 µmol/L; 95% CI −11.54 to −4.63) with adverse events comparable to controls. Despite homocysteine lowering, folate did not significantly reduce cardiovascular events, all-cause mortality, or cardiovascular mortality. Limited data suggested no clear improvement in serum creatinine, and evidence on long-term kidney disease progression was inconsistent. Subgroup signals in end-stage kidney disease, higher doses, or alternative folate forms did not reach statistical significance. 3

Conventional diet and pharmacologic strategies remain central for preventing recurrent calcium stones

This systematic review synthesized 31 studies, mostly randomized trials, of diet, pharmacologic therapy, and surveillance for recurrent nephrolithiasis. For adults with calcium oxalate or phosphate stones, increased water intake and a normal-to-high calcium, low-protein, low-sodium diet may reduce recurrence. Thiazide diuretics, alkali therapy, and allopurinol also may lower recurrence risk, though strength of evidence is generally low. Selective versus empirical pharmacotherapy showed no clear difference in recurrence outcomes based on low-strength evidence. Acetohydroxamic acid may reduce growth of infection-related stones but likely increases adverse events, with insufficient data on recurrence prevention. 4