Is population-wide diuretic use directly associated with the incidence of end-stage renal disease in the United States? A hypothesis

Abstract

Background: We introduce the hypothesis that population-wide use of diuretics might be associated with acceleration of the incidence of end-stage renal disease (ESRD).

Methods: Based on the technique of data fusion, pooled-data trends in disease incidence and antihypertensive medication use were examined to determine whether changes in drug use patterns are predictive of disease emergence in the United States. National databases for all-cause cardiovascular disease (CVD) mortality and stroke mortality from the National Vital Statistics Registry, renal failure data obtained from the United States Renal Data Service, and drug information obtained from IMS Health (Fairfield, CT) were examined.

Results: A statistically significant inverse relationship was observed between all-cause CVD mortality rates and ESRD incidence rates for the period 1980 to 1998 (r = -0.98948; P < .0001). A statistically significant direct time-lagged relationship was found between both annual changes in diuretic distribution and total diuretic expenditure to annual changes in the ESRD growth rate (r = 0.754, P = .03, r(2) = 0.568, 95% CI for slope = 0.08975 to 1.3010).

Conclusions: Increasing annual diuretic distribution in the US is directly associated with accelerated time-lagged growth rates of ESRD incidence. One potential explanation is that diuretic therapy could promote ESRD expression. A large-scale, randomized, controlled trial to investigate acceleration of ESRD by diuretics would be justifiable. The data invites the hypothesis that reliance on nondiuretic antihypertensive therapies such as calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers might attenuate the epidemic rise of ESRD that is prevalent in the United States.