title: 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.
authors.affiliation: Hypertension Institute, St.Thomas Hospital, Nashville, Tennessee, USA. rhawkins@stthomas.org
authors.forename: Ralph G
authors.initials: RG
authors.lastname: Hawkins
authors.forename: Mark C
authors.initials: MC
authors.lastname: Houston
mesh_terms: D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000401:mortality; D004232:Diuretics / Q000009:adverse effects* / Q000627:therapeutic use; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006304:Health Status; D006801:Humans; D015994:Incidence; D007676:Kidney Failure, Chronic / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D011159:Population Surveillance; D015995:Prevalence; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D014481:United States / Q000453:epidemiology
chemical_list: D004232:Diuretics