Aim: Romosozumab is increasingly prescribed across the spectrum of chronic kidney disease (CKD), yet its stage-specific renal and calcium safety in real-world Asian populations is poorly characterised. We assessed the 12-month trajectory of estimated glomerular filtration rate (eGFR) and hypocalcemia incidence by baseline CKD stage.

Methods: Retrospective multicentre cohort of patients completing 12-month subcutaneous romosozumab (210 mg monthly; 2019-2025) at two Japanese hospitals, stratified by KDIGO stage. Patients with paired pre/12-month eGFR were analysed (n=409). Endpoints were 12-month eGFR change (compared across stages, site-adjusted) and incidence of mild (albumin-corrected Ca <8.4 mg/dL), moderate (<8.0) and severe (<7.5) hypocalcemia. Per-stage ANCOVA (12-month eGFR on baseline) distinguished true effect from regression to the mean.

Results: Overall 12-month eGFR change was -3.64 mL/min/1.73m2 (95% CI, -4.76 to -2.53). Change differed across stages (p<0.001): -12.74, -3.35, -0.93 and +2.24 for stages 1, 2, 3 and 4-5, with no significant decline in stage 3 (p=0.28) or 4-5 (p=0.22). ANCOVA slopes rose from 0.31 (stage 1) to 1.14 (stage 4-5), indicating the stage-1 decline was predominantly regression to the mean. A >25% eGFR decline occurred in 8.8%. Mild hypocalcemia was 0.49% (2/407), confined to stages 4-5; one moderate, no severe events; mean corrected calcium was unchanged (p=0.33).

Conclusion: Romosozumab did not accelerate renal decline across CKD stages 1-5; the apparent stage-1 fall reflected regression to the mean. Hypocalcemia was rare and restricted to advanced CKD, supporting standard monitoring in stages 1-3 and intensified calcium/vitamin D supplementation with closer monitoring in stages 4-5.