Renal blood flow and progression to kidney failure in ADPKD

A decline in renal blood flow (RBF) precedes estimated glomerular filtration rate (eGFR) decline among patients with autosomal dominant polycystic kidney disease (ADPKD) and inversely associates with disease severity and progression. However, it is unknown whether RBF independently predicts progression to kidney failure in patients with ADPKD.

379 participants with early-stage ADPKD (age 36.6 ± 8.5 years [mean ± SD]; eGFR: 92.9 ± 17.1 mL/min/1.73m2) who participated in the HALT PKD Study A with baseline RBF (phase contrast MRI) data were included in the primary analysis. Kaplan Meier survival analysis and multivariate Cox proportional hazard models were used to determine the association of baseline RBF as a continuous and categorical variable with kidney failure risk (during HALT and subsequently linked to the US Renal Data System) over a median (IQR) follow-up period of 13.1 (7.5, 14.5) years (primary outcome). All-cause mortality was also considered as a competing risk (Fine and Gray method). The associations of RBF with eGFR slope and ∆ height-adjusted total kidney volume (htTKV) were evaluated with linear and logistic regression models.

The kidney failure incidence rate was the highest among those with the lowest RBF tertile (1.90 [1.31, 2.78] vs. 0.34 [0.14, 0.83] events/100 person-years in tertile 3). In the fully adjusted model, the lowest RBF tertile was associated with higher risk of progression to kidney failure (Hazard Ratio [HR (95% CI)] 3.19 [1.05, 9.67] vs. highest tertile). The association of RBF with kidney failure risk was slightly attenuated in adjusted models. All associations remained similar when considering death as a competing risk (HR: 0.82 [95% CI 0.67, 1.00] per 100 ml/min/1.73m2 higher RBF). Higher RBF was associated with slower eGFR decline and lower odds of rapid annual ∆htTKV.

Lower baseline RBF independently associates with greater risk of progression to kidney failure in early-stage patients with ADPKD.