You, Zhiying

Key Points In an observational cohort of mostly non-Hispanic White women, pregnancy was not associated with later-life accelerated kidney function decline. Pregnancy occurring during the HALT Progression of Polycystic Kidney Disease (HALT-PKD) trial was not associated with kidney disease progression relative to women who did not become pregnant. Prior evidence indicates that adverse pregnancy outcomes may be involved in autosomal dominant polycystic kidney disease progression; pregnant women should be closely monitored. Background Data are conflicting regarding whether pregnancy influences disease progression in women with autosomal dominant polycystic kidney disease (ADPKD). This study examined whether pregnancy or number of pregnancies was associated with kidney disease progression in women with ADPKD. Methods Women with early- (study A) and late-stage (study B) ADPKD from the HALT Progression of Polycystic Kidney Disease (HALT-PKD) trial were included to examine the association between self-reported number of pregnancies (categorical predictor: no pregnancy versus 1–2 pregnancies and ≥3 pregnancies), annual slope of eGFR, annual percent change in total kidney volume (%ΔTKV), and a composite outcome (kidney failure, 50% decline in eGFR, or death) using multivariable linear regression and Cox proportional hazard models. In addition, women who became pregnant, had full-term pregnancies, and available data during study participation ( n =13) were propensity matched (1:4) to women who were not pregnant during study participation, and a mixed model was applied to determine the association of pregnancy with eGFR slope and %ΔTKV. Results Across all analyses, 455 women with a median age of 45 (interquartile range, 38–50) years and eGFR of 69±25 ml/min per 1.73 m 2 at baseline were included. One hundred ninety-nine women had 1–2 pregnancies, and 165 women had ≥3 pregnancies. There was no association of 1–2 pregnancies or ≥3 pregnancies (versus no pregnancies) with eGFR slope ( β -estimate [95% confidence interval (CI)]; 1–2 pregnancies: 0.22 [−0.44 to 0.89]; ≥3 pregnancies: −0.46 [−1.16 to 0.25]), %ΔTKV ( β -estimate [95% CI]; 1–2 pregnancies: 0.92 [−0.34 to 2.17]; ≥3 pregnancies: 0.69 [−0.67 to 2.04]), or time to composite outcome (hazard ratio [95% CI]; 1–2 pregnancies: 1.04 [0.56 to 1.93]; ≥3 pregnancies: 1.48 [0.78 to 2.77]) in adjusted models. Moreover, there was no difference in annual eGFR slope ( β -estimate: −0.14 [95% CI, −2.72 to 2.44]) and %ΔTKV ( β -estimate: 0.04 [95% CI, −3.74 to 3.82]) in women who became pregnant matched to women who did not became pregnant during their participation in the study. Conclusions Pregnancy was not associated with ADPKD progression among women with early- and late-stage ADPKD enrolled in the HALT-PKD trial.

ABSTRACT Background A decrease 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. Methods A total of 379 participants with early-stage ADPKD (mean age 36.6 ± 8.5 years; eGFR: 92.9 ± 17.1 ml/min/1.73 m2) who participated in the Halt Progression of Polycystic Kidney Disease Study A (HALT PKD A; NCT00283686) with baseline RBF (phase contrast magnetic resonance imaging) 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 the HALT study and subsequently linked to the US Renal Data System) over a median follow-up period of 13.1 years (interquartile range 7.5–14.5) (primary outcome). All-cause mortality was also considered as a competing risk (Fine and Gray method). The associations of RBF with eGFR slope and the change in height-adjusted total kidney volume (∆htTKV) were evaluated with linear and logistic regression models. Results The kidney failure incidence rate was the highest among those with the lowest RBF tertile {1.90 [95% confidence interval (CI) 1.31–2.78] versus 0.34 [95% CI 0.14–0.83] events/100 person-years in tertile 3}. In the fully adjusted model, the lowest RBF tertile was associated with a higher risk of progression to kidney failure [hazard ratio (HR) 3.19 (95% CI 1.05–9.67] versus the 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/1.73 m2 higher RBF]. Higher RBF was associated with a slower eGFR decline and lower odds of rapid annual ∆htTKV. Conclusions Lower baseline RBF independently associates with a greater risk of progression to kidney failure in early-stage patients with ADPKD.