Beyond the Average Patient: A Population-Focused Review of Sodium-Glucose Cotransporter 2 Inhibitors in Autosomal Dominant Polycystic Kidney Disease

Sodium-glucose cotransporter 2 (SGLT2) inhibitors slow the loss of kidney function across a wide range of causes of chronic kidney disease (CKD).Still, the trials that established this benefit excluded autosomal dominant polycystic kidney disease (ADPKD) because these drugs raise vasopressin, the main hormonal driver of cyst growth.Since then, observational studies, a small crossover trial, and two meta-analyses with differing conclusions have appeared.This review argues that the question of whether SGLT2 inhibitors work in ADPKD cannot be answered for the disease as a whole, because ADPKD varies widely in genotype, rate of progression, CKD stage, comorbidity, and tolvaptan use.In this structured narrative review, PubMed and ClinicalTrials.govwere searched, and the clinical, trial, and preclinical evidence was mapped to these patient groups.Thirteen clinical studies were identified (two randomised, four comparative cohorts, four single-arm studies and three case reports), most of them small, short, and from Japan.The reassuring data come from two groups: older patients, many with type 2 diabetes or cardiovascular disease, whose kidney decline may owe as much to comorbidity as to cysts; and a few rapidly progressing patients already taking tolvaptan, in whom the only randomised trial reporting kidney outcomes found slower kidney growth and a better estimated glomerular filtration rate (eGFR) slope despite higher vasopressin.The evidence is almost silent on young, rapidly progressive patients not taking tolvaptan, the group in whom the concern about cyst growth is greatest, and the few case-level data in this group show kidney enlargement and falling eGFR.No study reports results by genotype or Mayo imaging class beyond individual case descriptions, and there are few or no data for slow progressors, early CKD, or heart failure.Phase 3 trials will answer the question for rapid progressors off tolvaptan from about 2030, but not for most other groups.Until then, SGLT2 inhibitors seem reasonable when there is a diabetic or heart-failure indication, based on evidence in those conditions rather than in ADPKD.The KDIGO guideline, although the Kidney Disease: Improving Global Outcomes (KDIGO) guideline does not yet recommend them in ADPKD.They should be considered within trials for rapid progressors, and should not be used off tolvaptan solely to slow ADPKD.Future trials should report results by genotype, imaging class, and tolvaptan use.