Renal endpoints in renal and cardiovascular randomized clinical trials: time for a consensus?

Fundam Clin Pharmacol. 2012 Dec;26(6):771-82. doi: 10.1111/j.1472-8206.2011.00965.x. Epub 2011 Aug 19.

Abstract

Several recent major randomized clinical trials (RCTs) using renal outcomes resulted in conflicting results. We searched MEDLINE via PubMed with the search request '(dialysis OR end-stage renal disease) and creatinine' in six major general journals and two leading journals of nephrology; 123 articles were found; 17/123 were relevant RCTs. Some disagreement among surrogate endpoints in 11/15 articles (missing data in two RCTs) and between surrogate and hard renal endpoints in 10/13; the intervention effects were in the opposite direction in 4/15, mostly in patients with cardiovascular disease, but discrepancies and conflicting results were also found among renal trials. Among our selected RCTs, 14/17 used composite endpoints: vital and renal endpoints were mixed in 11/14 trials, the components of the composite endpoints were of similar importance in 0/14 trials and of similar frequency in 1/11 trials, the intervention was likely to have a similar effect on the components in 4/14 trials, and the relative risk reduction was similar for the different components in 2/10 trials. None of the trials fulfiled all conditions of validation. Based on this analysis, we believe that the current use of renal endpoints in RCTs must be reviewed and their conditions of validation defined.

Publication types

  • Review

MeSH terms

  • Biomarkers / blood*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / drug therapy
  • Drugs, Investigational / administration & dosage
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / therapeutic use
  • Endpoint Determination*
  • Humans
  • Kidney Diseases / blood*
  • Kidney Diseases / chemically induced
  • Kidney Diseases / drug therapy
  • Kidney Function Tests
  • Randomized Controlled Trials as Topic / methods*
  • Randomized Controlled Trials as Topic / standards

Substances

  • Biomarkers
  • Drugs, Investigational