Longitudinal causal effect of modified creatinine index on all-cause mortality in patients with end-stage renal disease: Accounting for time-varying confounders using G-estimation

BACKGROUND: Standard regression modeling may cause biased effect estimates in the presence of time-varying confounders affected by prior exposure. This study aimed to quantify the relationship between declining in modified creatinine index (MCI), as a surrogate marker of lean body mass, and mortality among end stage renal disease (ESRD) patients using G-estimation accounting appropriately for time-varying confounders. METHODS: A retrospective cohort of all registered ESRD patients (n = 553) was constructed over 8 years from 2011 to 2019, from 3 hemodialysis centers at Kerman, southeast of Iran. According to changes in MCI, patients were dichotomized to either the decline group or no-decline group. Subsequently the effect of interest was estimated using G-estimation and compared with accelerated failure time (AFT) Weibull models using two modelling strategies. RESULTS: Standard models demonstrated survival time ratios of 0.91 (95% confidence interval [95% CI]: 0.64 to 1.28) and 0.84 (95% CI: 0.58 to 1.23) in patients in the decline MCI group compared to those in no-decline MCI group. This effect was demonstrated to be 0.57 (-95% CI: 0.21 to 0.81) using G-estimation. CONCLUSION: Declining in MCI increases mortality in patients with ESRD using G-estimation, while the AFT standard models yield biased effect estimate toward the null.