title: The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease.
abstract: BACKGROUND
  It is not known whether angiotensin-converting-enzyme (ACE) inhibitors slow the progression of polycystic kidney disease (PKD). We performed a patient-level meta-analysis to compare the effect of antihypertensive regimens, including ACE inhibitors, to those without ACE inhibitors (controls) on kidney disease progression in patients with PKD.
  
  
  METHODS
  We analyzed a database of 11 randomized controlled trials including 1860 patients with nondiabetic kidney disease. We compared randomized groups for the decline in urine protein excretion and kidney disease progression (combined outcome of doubling of baseline serum creatinine or onset of kidney failure). We also performed multivariable linear regression and Cox proportional hazards analyses. Based on previous findings, we searched for interactions between the treatment effect (effect of ACE inhibitors vs. controls) and baseline urine protein excretion in both models.
  
  
  RESULTS
  Eight studies included a total of 142 subjects with PKD: 68 (48%) were randomized to ACE inhibitors and 74 (52%) were randomized to the control. Baseline mean (SD) urine protein excretion was 0.92 (1.40) g/day: 1.08 (1.50) g/day in the ACE inhibitor and 0.76 (1.28) g/day in the control group. During a mean follow-up of 2.3 years, mean (SD) urine protein excretion declined by 0.33 (1.11) g/day in the ACE inhibitor group and increased by 0.19 (0.88) g/day in the control group (P < 0.001). Kidney disease progression occurred in 50 patients: 20 patients (29%) in the ACE inhibitor group and 30 patients (41%) in the control group (P= 0.17). ACE inhibitors had a greater effect on lowering urine protein excretion and slowing kidney disease progression in patients with higher levels of baseline urine protein excretion (interaction P < 0.001 and P= 0.03, respectively).
  
  
  CONCLUSIONS
  As in other causes of non-diabetic kidney disease, antihypertensive regimens with ACE inhibitors are more effective in lowering urine protein excretion in patients with advanced PKD compared to regimens without ACE inhibitors, and this benefit is greater in patients with higher levels of baseline urine protein excretion. The effect of ACE inhibitors to slow kidney disease progression in PKD is inconclusive.
authors.affiliation: Division of Nephrology, New England Medical Center, Boston, Massachusetts, USA. tazeen.jafar@aku.edu
authors.forename: Tazeen H
authors.initials: TH
authors.lastname: Jafar
authors.forename: Paul C
authors.initials: PC
authors.lastname: Stark
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Schmid
authors.forename: Svend
authors.initials: S
authors.lastname: Strandgaard
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Kamper
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maschio
authors.forename: Gavin
authors.initials: G
authors.lastname: Becker
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Perrone
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D016208:Databases, Factual; D006801:Humans; D015999:Multivariate Analysis; D007690:Polycystic Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology / Q000652:urine; D016016:Proportional Hazards Models; D011507:Proteinuria / Q000188:drug therapy / Q000209:etiology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors