title: Therapeutic response to vasoconstrictors in hepatorenal syndrome parallels increase in mean arterial pressure: a pooled analysis of clinical trials.
abstract: BACKGROUND
  Vasoconstrictor therapy has been advocated as treatment for hepatorenal syndrome (HRS). Our aim was to explore across all tested vasoconstrictors whether achievement of a substantial increase in arterial blood pressure is associated with recovery of kidney function in HRS.
  
  
  METHODS
  Pooled analysis of published studies identified by electronic database search.
  
  
  METHODS
  Data pooled across 501 participants in 21 studies.
  
  
  METHODS
  Human studies evaluating the efficacy of a vasoconstrictor administered for 72 hours or longer in adults with HRS type 1 or 2.
  
  
  METHODS
  Vasoconstrictor therapy.
  
  
  METHODS
  Cohorts' mean arterial pressure (MAP), serum creatinine level, urinary output, and plasma renin activity (PRA) at baseline and subsequent times during treatment. Linear regression models were constructed to estimate mean daily changes in MAP, serum creatinine level, urinary output, and PRA for each study subgroup. Correlations were used to assess for association between variables.
  
  
  RESULTS
  An increase in MAP is associated strongly with a decrease in serum creatinine level, but is not associated with an increase in urinary output. Associations were stronger when analyses were restricted to randomized clinical trials and were not limited to cohorts with either lower baseline MAP or lower baseline serum creatinine level. Most studies tested terlipressin as vasoconstrictor, whereas fewer studies tested ornipressin, midodrine, octreotide, or norepinephrine. Excluding cohorts of participants treated with terlipressin or ornipressin did not eliminate the association. Furthermore, a decrease in PRA correlated with improvement in kidney function.
  
  
  CONCLUSIONS
  Studies were not originally designed to test our question. We lacked access to individual patient data.
  
  
  CONCLUSIONS
  An increase in MAP during vasoconstrictor therapy in patients with HRS is associated with improvement in kidney function across the spectrum of drugs tested to date. These results support consideration for a goal-directed approach to the treatment of HRS.
authors.affiliation: Division of Nephrology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA. velezj@musc.edu
authors.forename: Juan Carlos Q
authors.initials: JC
authors.lastname: Velez
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Nietert
mesh_terms: D001794:Blood Pressure / Q000187:drug effects*; D003404:Creatinine / Q000097:blood; D006530:Hepatorenal Syndrome / Q000188:drug therapy* / Q000503:physiopathology*; D006801:Humans; D020127:Recovery of Function / Q000502:physiology; D012083:Renin / Q000097:blood; D014556:Urine; D014662:Vasoconstrictor Agents / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D014662:Vasoconstrictor Agents; D003404:Creatinine; D012083:Renin