Renal blood flow as marker for disease progression in autosomal dominant polycystic kidney disease

Background Disease progression in autosomal dominant polycystic kidney disease (ADPKD) is variable. Renal blood flow (RBF) and filtration fraction (FF), reflecting hemodynamic alterations and hyperfiltration, may improve risk stratification. Methods This prospective study included 238 adults with ADPKD from the DIPAK observational cohort study and 1421 healthy controls. Multivariable regression analyses assessed associations of RBF and FF with disease severity and progression. Kaplan-Meier analysis and classification performance metrics were used to evaluate clinical utility beyond established risk stratification tools. Results Cross-sectionally, patients with ADPKD had significantly lower RBF than controls across all age groups, even in young patients with similar eGFR to controls. Within ADPKD patients, lower RBF was associated with reduced kidney function and larger kidney volume. During follow-up of 5.6 ± 3.5 years, higher RBF (per SD) was associated with slower annual eGFR decline (standardized β = 0.34, 95% CI: 0.09-0.58, P=0.01), lower odds of rapid disease progression (eGFR decline ≥3.0 mL/min/1.73 m 2 per year) (OR = 0.34, 95% CI: 0.17-0.70, P=0.003) and lower composite-endpoint risk (kidney failure or ≥30% eGFR decline) (HR = 0.35, 95% CI: 0.20-0.60, P < 0.001). FF was significantly higher in patients aged 30-40 years, consistent with early hyperfiltration, but was not associated with disease progression. For the association with rapid progression, adding RBF to the Mayo Imaging Classification (MIC) increased the AUC from 0.69 (95% CI: 0.60-0.76) to 0.79 (95% CI: 0.72-0.85). Conclusion Reduced RBF is an early hallmark of ADPKD, associated with disease severity and kidney function decline, and improves risk stratification beyond MIC.