title: Prostaglandin E1 analogs do not improve renal function among either transplant or nontransplant patients: no further trials required.
abstract: BACKGROUND
  To assess whether prostaglandin E1 analogs have a role in either reducing renal allograft rejection or improving renal function among both transplant and nontransplant patients.
  
  
  METHODS
  Studies were identified through Ovid MEDLINE between 1981 and December 1997 using multiple MeSH headings and text words related to renal or liver transplantation, as well as renal insufficiency. These items were crossed with MeSH headings and text words related to prostaglandins and prostaglandin E1. All abstracts were read, in addition to review articles, and their bibliographies were searched for further references. Articles were limited to those published in the English language. Studies were selected based on the following criteria: (1) a randomized control clinical trial; (2) administration of any form of prostaglandin; (3) publication of primary data; and (4) reporting on either renal transplant rejection or renal dysfunction after transplant or, for both transplant and nontransplant studies, objectively comparing a change in renal function from before to after prostaglandin E1 therapy. From the 217 articles that were retrieved, 19 met all inclusion criteria. Data were extracted on study design, nature of the study subjects, and the principal therapeutic intervention. Among the transplant studies, the rate of acute renal graft rejection or renal dysfunction was calculated for each study and then pooled using a random effects model. In addition, the mean change in renal glomerular filtration rate was compared between prostaglandin E1 and controls among both transplant and nontransplant studies and then pooled using an inverse variance-weighted method. Using the Breslow-Day method, statistical heterogeneity was defined at a two-sided P value less than 0.10.
  
  
  RESULTS
  Within the 10 transplant trials, all patients were on cyclosporine; oral or intravenous prostaglandin E1 was generally started within 24 hr of transplantation. Renal transplant rejection or renal dysfunction was not significantly reduced with prostaglandin E1 (odds ratio 0.91, 95% confidence interval [CI] 0.64 to 1.28, two-sided P value=0.58; weighted control event 66.9%, 95% CI 50.5 to 80.0). The glomerular filtration rate was estimated within nine transplant studies, with a minimal positive gain in renal function with prostaglandin E1 (mean difference 2.3 ml/min, 95% CI 1.6 to 3.1). Nine other randomized, double-blinded trials evaluated the effect of prostaglandin E1 on renal function among a variety of nontransplant patients. These patients were generally selected based on their susceptibility to renal injury, with a concomitant exposure to nonsteroidal anti-inflammatory drugs. No significant change in the glomerular filtration rate was observed between prostaglandin E1 and placebo arms (mean difference 0.5 ml/min in favor of placebo, 95% CI -2.8 to 1.8). However, these studies were very heterogeneous.
  
  
  CONCLUSIONS
  Among both transplant and nontransplant populations, prostaglandin E1 does not seem to preserve or improve renal function. Further research is unlikely to demonstrate superiority of prostaglandin E1 in the context of cyclosporine or nonsteroidal anti-inflammatory drug use.
authors.affiliation: Department of Medicine, Women's College Hospital, University of Toronto, Ontario, Canada.
authors.forename: J G
authors.initials: JG
authors.lastname: Ray
mesh_terms: D000527:Alprostadil / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007668:Kidney / Q000502:physiology*; D016030:Kidney Transplantation / Q000502:physiology*; D016032:Randomized Controlled Trials as Topic
chemical_list: D000527:Alprostadil