Background: Obesity substantially increases the risk of the development of chronic kidney disease. Adipose tissue expresses all of the components of the renin-angiotensin system (RAS), contributing to the high prevalence of hypertension in obese patients and driving renal hyperfiltration and subsequent glomerular injury. Methods: We performed a retrospective cohort study using a United Kingdom primary care database, evaluating the effect of time-updated exposure to RAS blockade versus all other antihypertensive medications in obese, hypertensive, non-diabetic patients. We used Cox proportional hazards modeling with and without marginal structural modeling to assess the hazards of developing a primary outcome of 50% reduction in estimated glomerular filtration rate (eGFR) (across 2 consecutive values), end stage renal disease or death. Results: A total of 219,701 patients met inclusion criteria, with a median 7.2 years of follow-up. Median baseline eGFR was 72.6 ml/min/1.73 m2. Compared to other antihypertensive medications, patients treated with RAS blockade had a modestly elevated hazard of adverse renal outcomes using traditional Cox regression (hazard ratio (HR) 1.04, 95% CI 1.01-1.07) and no significantly increased hazard by marginal structural modeling (HR 1.02, 95% CI 0.97-1.08). Patients treated with RAS blockade had a significantly reduced hazard of incident diabetes, but no significant difference in mortality. Conclusion: This study, conducted in a large real-world cohort, provides evidence that RAS blockade may not provide benefit with regard to longitudinal renal outcomes in obese, hypertensive patients. Further research is needed to elucidate the hemodynamic and renoprotective role of antihypertensive medications in obese patients.
Super learning to hedge against incorrect inference from arbitrary parametric assumptions in marginal structural modeling