ObjectiveAutosomal dominant polycystic kidney disease (ADPKD) is a progressive hereditary kidney disorder with limited treatment options. Although semaglutide has demonstrated kidney-protective effects in other populations, its renal effects in ADPKD remain unknown.MethodsWe conducted a retrospective propensity score-matched cohort study using the TriNetX Research Network. Adults with ADPKD between 2000 and 2024 were identified. Patients receiving sodium-glucose cotransporter-2 inhibitors, tolvaptan, or other glucagon-like peptide-1 receptor agonists were excluded. Semaglutide users were matched 1:1 with non-users. Outcomes included creatinine-based estimated glomerular filtration rate (eGFR), stage 5 chronic kidney disease (CKD), end-stage kidney disease (ESKD), body mass index (BMI), acute kidney injury (AKI), urinary tract infection (UTI), volume depletion, and all-cause mortality.ResultsAmong 45,613 adults with ADPKD, 323 semaglutide users and 31,300 non-users met the eligibility criteria; 320 matched pairs were analyzed. At follow-up, semaglutide users had a higher mean creatinine-based eGFR than non-users (57.52 ± 28.19 vs. 50.93 ± 33.80 mL/min/1.73 m2; p = 0.013) and a lower risk of progression to stage 5 CKD (hazard ratio, 0.447; 95% confidence interval, 0.230-0.872). No significant differences were observed in ESKD, AKI, or UTI. Semaglutide use was also associated with lower incidences of volume depletion and all-cause mortality.ConclusionsSemaglutide use was associated with higher follow-up eGFR of creatinine-based eGFR and a lower risk of stage 5 CKD in patients with ADPKD. Because semaglutide-induced weight loss and reductions in muscle mass may lower serum creatinine independently of true glomerular filtration, the observed preservation of creatinine-based eGFR should be interpreted cautiously. Given the observational design, limited follow-up, and potential residual confounding, these findings should be considered hypothesis-generating and require confirmation in prospective studies.
