Abstract
Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive renal cyst development and variable trajectories toward end-stage renal disease (ESRD). Hypertension is both common and prognostically significant in ADPKD. However, the escalating need for antihypertensive agents beyond RAAS inhibition on disease progression remains underexplored. Methods: We conducted a retrospective, single-center cohort study including 133 ADPKD patients followed for a median of 5 years. Baseline clinical, biochemical, and genetic data were collected. The primary outcome was a ≥25% decline in eGFR over 5 years. All patients achieved a blood pressure target range of 110/70 to 130/85 mmHg during follow-up. Univariate and multivariate logistic regression analyses were performed to identify predictors of rapid progression. Results: Patients with hypertension resistant to RAAS (i.e., those requiring additional antihypertensive drugs on top of RAAS inhibitors) had significantly higher odds of rapid eGFR decline (multivariate OR 1.27; 95% CI 1.03-1.57; p = 0.0248). The presence of hypertension resistant to RAAS was interpreted as a potential clinical surrogate for a more aggressive cystic phenotype and intrarenal hemodynamic dysregulation. Conclusions: Hypertension resistant to RAAS is an independent predictor of accelerated renal function decline in ADPKD. Its identification may aid in early risk stratification and prompt consideration of disease-modifying therapies such as tolvaptan. Further validation in larger cohorts is warranted.