title: Creatinine Change on Vasoconstrictors as Mortality Surrogate in Hepatorenal Syndrome: Systematic Review & Meta-Analysis.
abstract: OBJECTIVE
  Hepatorenal syndrome is a severe complication of cirrhosis and associates with significant mortality. Vasoconstrictor medications improve renal function in patients with hepatorenal syndrome. However, it is unclear to what extent changes in serum creatinine during treatment may act as a surrogate for changes in mortality. We have performed a meta-analysis of randomized trials of vasoconstrictors assessing the association between changes in serum creatinine, taken as a continuous variable, and mortality, both while on treatment and during the follow-up period for survivors.
  
  
  METHODS
  The electronic databases of PubMed, Web of Science and Embase were searched for randomized trials evaluating the efficacy of vasoconstrictor therapy for treatment of HRS type 1 or 2. The relative risk (RR) for mortality was calculated against delta creatinine. The proportion of treatment effect explained (PTE) was calculated for delta creatinine.
  
  
  RESULTS
  Seven trials enrolling 345 patients were included. The correlation between delta creatinine and ln (RR) was moderately good (R2 = 0.61). The intercept and parameter estimate indicated a fall in creatinine while on treatment of 1 mg/dL resulted in a 27% reduction in RR for mortality compared to the control arm. In patients surviving the treatment period, a fall in creatinine while on treatment of 1 mg/dL resulted in a 16% reduction in RR for post-treatment mortality during follow-up. The PTE of delta creatinine for overall mortality was 0.91 and 0.26 for post-treatment mortality.
  
  
  CONCLUSIONS
  Changes in serum creatinine in response to vasoconstrictor therapy appear to be a valid surrogate for mortality, even in the period following the completion of treatment.
authors: Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT, United States of America; Section of Nephrology, Yale University School of Medicine, New Haven, CT, United States of America; Clinical Epidemiology Research Center, VAMC, West Haven, CT, United States of America.
authors: Justin M
authors: JM
authors: Belcher
authors: Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT, United States of America; Section of Nephrology, Yale University School of Medicine, New Haven, CT, United States of America; Clinical Epidemiology Research Center, VAMC, West Haven, CT, United States of America.
authors: Steven G
authors: SG
authors: Coca
authors: Program of Applied Translational Research, Yale University School of Medicine, New Haven, CT, United States of America; Section of Nephrology, Yale University School of Medicine, New Haven, CT, United States of America; Clinical Epidemiology Research Center, VAMC, West Haven, CT, United States of America.
authors: Chirag R
authors: CR
authors: Parikh
mesh_terms: D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood*; D006530:Hepatorenal Syndrome / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008236:Lypressin / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D016019:Survival Analysis; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D014662:Vasoconstrictor Agents; D008236:Lypressin; D003404:Creatinine