Clinical Nephrology – Epidemiology – Clinical Trials
Kidney International (2005) 67, 265–271; doi:10.1111/j.1523-1755.2005.00077.x
The effect of angiotensin-converting-enzyme inhibitors on progression of advanced polycystic kidney disease
TAZEEN H JAFAR, PAUL C STARK, CHRISTOPHER H SCHMID, SVEND STRANDGAARD, ANNE-LISE KAMPER, GIUSEPPE MASCHIO, GAVIN BECKER, RONALD D PERRONE and ANDREW S LEVEY FOR THE ACE INHIBITION IN PROGRESSIVE RENAL DISEASE (AIPRD) STUDY GROUP
Division of Nephrology, New England Medical Center, Boston, Massachusetts; Department of Medicine, The Aga Khan University, Karachi, Pakistan; Department of Community Health Sciences, The Aga Khan University, Karachi, Pakistan; Division of Clinical Care Research, New England Medical Center, Boston, Massachusetts; Department of Nephrology, Herlev Hospital University of Copenhagen, Copenhagen, Denmark; Division Nefrologia Ospedale Civile Maggiore, Verona, Italy; and The Royal Melbourne Hospital, Melbourne, Australia
Correspondence: Tazeen H. Jafar, M.D., M.P.H., Head, Section of Nephrology, Director, Clinical Epidemiology Unit, Associate Professor, Departments of Medicine and Community Health Sciences, Aga Khan University, Stadium Road, PO Box 3500, Karachi, Pakistan. E-mail:tazeen.jafar@aku.edu
Received 5 May 2004; Revised 14 July 2004; Accepted 27 July 2004.
Abstract
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).
Conclusion
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.
Keywords:
polycystic kidney disease, kidney disease progression, ACE inhibitors
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