The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease.
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.
Jafar
Tazeen H
TH
Division of Nephrology, New England Medical Center, Boston, Massachusetts, USA. tazeen.jafar@aku.edu
Stark
Paul C
PC
Schmid
Christopher H
CH
Strandgaard
Svend
S
Kamper
Anne-Lise
AL
Maschio
Giuseppe
G
Becker
Gavin
G
Perrone
Ronald D
RD
Levey
Andrew S
AS
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
D000806:Angiotensin-Converting Enzyme Inhibitors