Renal Calculi (Kidney Stones): Advances and Management

Kidney stones are crystalline deposits — most often calcium oxalate — managed through acute treatment, recurrence prevention, and, for rare metabolic forms, disease-specific therapy.

Prevention of calcium-stone recurrence

A notable recent finding tempered long-standing practice: in the NOSTONE trial, hydrochlorothiazide at 12.5, 25, or 50 mg daily did not significantly reduce stone recurrence versus placebo, and carried more adverse effects (hypokalemia, gout, new-onset diabetes). Thiazides may therefore be less effective for recurrence prevention than long assumed, and their use warrants individualized risk-benefit assessment. The general cornerstones remain robust: high fluid intake (2–2.5 L/day urine output), reduced sodium and animal protein, normal calcium intake, citrate supplementation for hypocitraturia, and allopurinol for hyperuricosuric stones.

RNA-targeted therapy for primary hyperoxaluria

The clearest advance is in primary hyperoxaluria type 1 (PH1), where the liver overproduces oxalate. Two RNА interference therapies now target this defect directly: lumasiran (which reduces oxalate synthesis upstream) markedly lowered urinary oxalate and achieved normalization in most patients in its pivotal trial and is approved for PH1; and nedosiran (Rivfloza), a once-monthly injection acting on hepatic lactate dehydrogenase, was approved in 2023 for PH1 in patients aged nine and older with relatively preserved kidney function. Together they transform the outlook for a disease that previously drove recurrent stones and progressive kidney failure. For cystinuria and struvite stones, tiopronin/penicillamine with alkalinization and infection eradication, respectively, remain the mainstays.

Further reading: NOSTONE hydrochlorothiazide (Dhayat et al., NEJM 2023); lumasiran ILLUMINATE (Garrelfs et al., NEJM 2021); nedosiran PHYOX program (2023); EAU/AUA urolithiasis guidelines.