title: Nephrotoxic Medication Exposure in U.S. Adults with Predialysis Chronic Kidney Disease: Health Services Utilization and Cost Outcomes.
abstract: BACKGROUND
  Nephrotoxic medication exposure increases risks for acute kidney injury, permanent renal function loss, and costly preventable adverse drug events. Exposure to medications associated with inducing acute tubular nephritis or tubular toxicity versus nonexposure among those with predialysis renal disease-a population vulnerable to increased risk of kidney injury-may affect health services utilization and cost outcomes. Few studies quantify nephrotoxic medication exposure in chronic kidney disease (CKD) and associated costs.
  
  
  OBJECTIVE
  To examine exposure to medications associated with inducing acute tubular nephritis or tubular toxicity versus nonexposure and the effect on health services utilization and cost outcomes in a nationally representative sample of adults with predialysis CKD.
  
  
  METHODS
  This retrospective study used Medical Expenditure Panel Survey (MEPS) household component longitudinal files (years 2006-2012; panels 11-16). Participants included 809 MEPS respondents aged > 18 years with predialysis CKD, after excluding those participants with cancer, kidney stone, renal dialysis, or transplant procedures (approximately 14.7 million U.S. noninstitutionalized individuals). Two groups were created to evaluate the main measures: (1) participants prescribed 1 or more medications associated with risk of acute tubular nephritis and/or tubular toxicity (termed "nephrotoxic exposure") and (2) participants with nonexposure. Medications cited in published literature as associated with tubular kidney damage were used. Multivariable regression models assessed the pattern of nephrotoxic medication exposure and its effect on health services utilization and expenses.
  
  
  RESULTS
  Nephrotoxic medication exposure occurred in 72% of adult MEPS respondents. Of those, 47.2% and 52.8% were prescribed 1 and at least 2 nephrotoxic medications, respectively. Coexistent chronic conditions included hypertension (72.3%), diabetes (49.5%), coronary heart disease (33%), arthritis (23.6%), and chronic obstructive pulmonary disease (17.6%). Eligible MEPS respondents aged ≥ 65 years, from the U.S. South region, and with Charlson Comorbidity Index (CCI) score > 0 were 75% (vs. aged 18-45 years), 83% (vs. Northeast), and 72%-96% (vs. CCI = 0) more likely to be exposed to nephrotoxic medications. Uninsured participants showed 55% less likelihood of nephrotoxic exposure, compared with privately insured participants. Higher utilization was shown in the nephrotoxic medication exposure group (vs. nonexposure): prescription fills (52.8 vs. 26.8, P < 0.001), emergency department visits (56.2 vs. 29.3 per 1,000 patient months, P < 0.001), and hospitalization (51.8 vs. 23.4 per 1,000 patient months, P < 0.001). Unadjusted all-cause expenses were greater for the following categories: medical ($119,935 vs. $11,462, P < 0.001), prescription drug ($4,828 vs. $2,816, P < 0.001), and total health expenses ($24,663 vs. $14,277, P < 0.001). Adjusted all-cause expenses were greater for total (29.7% greater, P = 0.003), prescription medications (56.6% greater, P < 0.001), and medical (23.4% greater, P = 0.036), but there were no differences in predialysis CKD-related utilization and expenses.
  
  
  CONCLUSIONS
  Increased vigilance is needed when prescribing nephrotoxic medications in predialysis CKD, particularly in patients with comorbid conditions and the elderly. Nephrotoxic medication exposure in predialysis CKD has the potential for increased health services utilization and cost outcomes.
  
  
  BACKGROUND
  There was no grant or intramural funding for this research. The authors have no conflicts of interest, financial or otherwise, to disclose. Study concept and design were primarily contributed by Davis-Ajami, along with Fink and Wu. Davis-Ajami took the lead in data collection, along with Wu, and data interpretation was performed by David-Ajami, Wu, and Fink. All authors participated in manuscript preparation and revision.
authors.affiliation: 1 Virginia Commonwealth University School of Nursing, Richmond, Virginia.
authors.forename: Mary Lynn
authors.initials: ML
authors.lastname: Davis-Ajami
authors.affiliation: 2 University of Maryland Medical System, Baltimore, Maryland.
authors.forename: Jeffery C
authors.initials: JC
authors.lastname: Fink
authors.affiliation: 3 Presbyterian College School of Pharmacy, Clinton, South Carolina.
authors.forename: Jun
authors.initials: J
authors.lastname: Wu
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000191:economics* / Q000453:epidemiology; D000293:Adolescent; D000328:Adult; D000368:Aged; D003365:Costs and Cost Analysis / Q000191:economics*; D003430:Cross-Sectional Studies; D064420:Drug-Related Side Effects and Adverse Reactions / Q000191:economics* / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D010342:Patient Acceptance of Health Care; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy / Q000191:economics* / Q000453:epidemiology; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology; D055815:Young Adult