In this study, we aimed to estimate the causal effect of normalized protein catabolic rate (nPCR) on mortality among end-stage renal disease (ESRD) patients in the presence of time-varying confounding affected by prior exposure using g-estimation. Information about 553 ESRD patients was retrospectively collected over an 8-year period (2011-2019) from hemodialysis facilities in Kerman, Iran. nPCR was dichotomized as <1.2 g/kg/day versus ≥1.2 g/kg/day. Then a standard time-varying accelerated failure time (AFT) Weibull model was built, and results were compared with those generated by g-estimation. After appropriate adjustment for time-varying confounders, weighted g-estimation yielded 78% shorter survival time (95% confidence interval (95% CI): -81, -73) among patients with a continuous nPCR <1.2 g/kg/day than among those who had nPCR ≥1.2 g/kg/day during follow-up, though it was 18% (95% CI: -57, 54) in the Weibull model. Moreover, hazard ratio estimates of 4.56 (95% CI: 3.69, 5.37) and 1.20 (95% CI: 0.66, 2.17) were obtained via weighted g-estimation and the Weibull model, respectively. G-estimation indicated that inadequate dietary protein intake characterized by nPCR increases all-cause mortality among ESRD patients, but the Weibull model provided an effect estimate that was substantially biased toward the null.
Keywords: G-estimation; epidemiologic methods; hemodialysis; mortality; time-varying confounding.
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