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Blood pressure and the risk of chronic kidney disease progression using multistate marginal structural models in the CRIC Study
Authors:Alisa J. Stephens‐Shields  Andrew J. Spieker  Amanda Anderson  Paul Drawz  Michael Fischer  Stephen M. Sozio  Harold Feldman  Marshall Joffe  Wei Yang  Tom Greene  CRIC Study Investigators
Affiliation:1. Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, U.S.A.;2. Department of Medicine, University of Minnesota, Minneapolis, U.S.A.;3. Department of Medicine, University of Illinois College of Medicine, Chicago, U.S.A.;4. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, U.S.A.;5. Department of Population Health Sciences, University of Utah School of Medicine, Salt Lake City, U.S.A.
Abstract:In patients with chronic kidney disease (CKD), clinical interest often centers on determining treatments and exposures that are causally related to renal progression. Analyses of longitudinal clinical data in this population are often complicated by clinical competing events, such as end‐stage renal disease (ESRD) and death, and time‐dependent confounding, where patient factors that are predictive of later exposures and outcomes are affected by past exposures. We developed multistate marginal structural models (MS‐MSMs) to assess the effect of time‐varying systolic blood pressure on disease progression in subjects with CKD. The multistate nature of the model allows us to jointly model disease progression characterized by changes in the estimated glomerular filtration rate (eGFR), the onset of ESRD, and death, and thereby avoid unnatural assumptions of death and ESRD as noninformative censoring events for subsequent changes in eGFR. We model the causal effect of systolic blood pressure on the probability of transitioning into 1 of 6 disease states given the current state. We use inverse probability weights with stabilization to account for potential time‐varying confounders, including past eGFR, total protein, serum creatinine, and hemoglobin. We apply the model to data from the Chronic Renal Insufficiency Cohort Study, a multisite observational study of patients with CKD.
Keywords:causal inference  inverse probability weighting  multistate models  renal disease progression
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