A three-year randomized, double-blind, placebo-controlled study of lanreotide in stage 2/3 autosomal dominant polycystic kidney disease.

Abstract

Somatostatin analogues reduce liver and kidney cyst volume in autosomal dominant polycystic kidney disease (ADPKD), but randomized trials have not demonstrated a consistent benefit on kidney function decline. We tested whether the analogue lanreotide slows glomerular filtration rate (GFR) decline over three years in adults with ADPKD stages 2/3. In this randomized, double-blind, placebo-controlled trial, we enrolled adults with ADPKD and measured GFR (mGFR) 30-89 mL/min/1.73 m². Patients were randomized to receive monthly injections of lanreotide 120 mg or 0.9% sodium chloride placebo for three years. The primary endpoint was mGFR slope (iohexol clearance) assessed at baseline, weeks 72 and 144 and analyzed with a linear mixed-effects model (LMM). Secondary endpoints included annual estimated GFR decline (creatinine-based, assessed at 11 scheduled visits), kidney events, quality of life, and safety. Due to slow enrollment, recruitment stopped after 144 of 180 planned participants. All randomized participants were included in the analysis (intention-to-treat). The primary endpoint was not met: the model-derived annualized between-arm difference in mGFR trajectory was -0.3 ml/min/1.73 m² per year (95% confidence interval -3.4 to 2.8). The time × lanreotide coefficient from the pre-specified creatinine-eGFR LMM was significant +1.2 ml/min/1.73 m² per year (0.27 to 2.15); however, this signal was not replicated by cystatin C-eGFR nor urinary creatinine clearance, consistent with a non-GFR effect on creatinine physiology. Rates of kidney events and quality-of-life scores were similar between arms. Gastrointestinal adverse events were more frequent with lanreotide. Hypoglycemia occurred in 11.1% of lanreotide-treated versus 1.4% of placebo-treated participants. Lanreotide did not slow mGFR decline in adults with stage 2/3 ADPKD. The creatinine-eGFR signal is exploratory, not supported by muscle-mass-independent markers, and should be interpreted in the context of a negative primary endpoint. An unexpected hypoglycemia signal warrants proactive monitoring when considering lanreotide in this population.