Prognostic significance of a reduced glomerular filtration rate and interaction with microalbuminuria in resistant hypertension

OBJECTIVE: The prognostic importance of a reduced glomerular filtration rate (GFR) is unsettled in resistant hypertension. The aim was to evaluate GFR and its interaction with microalbuminuria as prognostic predictors in resistant hypertensive patients. METHODS: In a prospective study, 531 resistant hypertensive patients had albuminuria measured and GFR estimated by Cockroft-Gault (eGFRCG) and Modification of Diet in Renal Disease (MDRD; eGFRMDRD) equations. Primary endpoints were a composite of fatal and nonfatal cardiovascular events, all-cause and cardiovascular mortality. Multiple Cox regression assessed the associations between reduced GFR and endpoints, and interaction with microalbuminuria. RESULTS: After a median follow-up of 4.9 years, 72 patients died, 42 from cardiovascular causes; and 96 cardiovascular events occurred. Decreasing grades of eGFRMDRD were predictors of the composite endpoint with hazard ratios of 2.1 [95% confidence interval (CI) 1.1-3.8], 2.2 (1.2-3.9) and 3.5 (1.4-8.7) for the subgroups with eGFR between 60-89, 30-59 and less than 30 mg/min per 1.73 m, respectively. A decreased eGFRCG was predictive of the composite endpoint only in the lowest GFR subgroup (hazard ratio 2.7, 95% CI 1.0-7.1). The lowest eGFR subgroups were also associated with all-cause mortality, regardless of the estimated equation used. The presence of both reduced eGFR and microalbuminuria significantly increased cardiovascular risk in relation to one or another isolated, with hazard ratios of 3.0 (1.7-5.3), 2.9 (1.5-5.5) and 4.6 (2.2-10.0), respectively for the composite endpoint, all-cause and cardiovascular mortality. CONCLUSION: A reduced GFR, mainly estimated by the MDRD equation, is an independent predictor of increased cardiovascular morbidity and mortality in resistant hypertension. The combination of a reduced GFR and increased albuminuria identifies patients with a very high cardiovascular risk.