Clinical Nephrology – Epidemiology – Clinical Trials
Kidney International (2001) 60, 1131–1140; doi:10.1046/j.1523-1755.2001.0600031131.x
Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease
Tazeen H Jafar, Paul C Stark, Christopher H Schmid, Marcia Landa, Guiseppe Maschio, Carmelita Marcantoni, Paul E De Jong, Dick De Zeeuw, Shahnaz Shahinfar, Piero Ruggenenti, Guiseppe Remuzzi, Andrew S Levey and for the AIPRD Study Group1
Division of Nephrology, and Division of Clinical Care Research, New England Medical Center, Boston, Massachusetts, USA; Divisone Nefrologia, Ospedale Civile Maggiore, Verona, Italy; University of Groningen, Groningen, The Netherlands; Merck Research Laboratories, West Point, New Jersey, USA; and "Mario Negri" Institute for Pharmacological Research, Bergamo, Italy
Correspondence: Andrew S. Levey, M.D., Division of Nephrology, New England Medical Center, Box 391, 750 Washington Street, Boston, Massachusetts 02111, USA
1Other members of the Angiotensin-Converting Enzyme Inhibition and Progression of Renal Disease (AIPRD) Study Group include: R. Toto (Dallas, TX, USA), B.M. Brenner (Boston, MA, USA), A. Kamper (Copenhagen, Denmark), P. Zucchelli (Malpighi-Bologna, Italy), G. Becker (Melbourne, Australia), A. Himmelmann (Goteborg, Sweden), K. Bannister (Adelaide, Australia), P. Landais (Paris, France), A. Perna (Bergamo, Italy), S. Strandgaard (Copenhagen, Denmark), B.U. Ihle (Melbourne, Australia), L. Hannson (Goteborg, Sweden), J.P. Grünfeld (Paris, France), G.G. Van Essen (Groningen, The Netherlands), A.J. Apperloo (Groningen, The Netherlands), L. Oldrizzi (Verona, Italy), N.E. Madias (Boston, MA, USA), B. Delano (Brooklyn, NY, USA), T. Karim (Boston, MA, USA), and M. Reddy (Boston, MA, USA).
Received 4 January 2001; Revised 9 April 2001; Accepted 16 April 2001.
Abstract
Proteinuria as a modifiable risk factor for the progression of non-diabetic renal disease.
Background
Angiotensin-converting enzyme (ACE) inhibitors reduce urine protein excretion and slow the progression of renal disease. The beneficial effect in slowing the progression of renal disease is greater in patients with higher urine protein excretion at the onset of treatment. We hypothesized that the greater beneficial effect of ACE inhibitors on the progression of renal disease in patients with higher baseline levels of proteinuria is due to their greater antiproteinuric effect in these patients.
Methods
Data were analyzed from 1860 patients enrolled in 11 randomized controlled trials comparing the effect of antihypertensive regimens, including ACE inhibitors to regimens not including ACE inhibitors on the progression of non-diabetic renal disease. Multivariable linear regression analysis was used to assess the relationship between the level of proteinuria at baseline and changes in urine protein excretion during follow-up. The Cox proportional hazards analysis was used to assess the relationship between changes in urine protein excretion during follow-up and the effect of ACE inhibitors on the time to doubling of baseline serum creatinine values or onset of end-stage renal disease.
Results
Mean (median) baseline urine protein excretion was 1.8 (0.94) g/day. Patients with higher baseline urine protein excretion values had a greater reduction in proteinuria during the follow-up in association with treatment with ACE inhibitors and in association with lowering systolic and diastolic blood pressures (interaction P < 0.001 for all). A higher level of urine protein excretion during follow-up (baseline minus change) was associated with a greater risk of progression [relative risk 5.56 (3.87 to 7.98) for each 1.0 g/day higher protein excretion]. After controlling for the current level of urine protein excretion, the beneficial effect of ACE inhibitors remained significant [relative risk for ACE inhibitors vs. control was 0.66 (0.52 to 0.83)], but there was no significant interaction between the beneficial effect of ACE inhibitors and the baseline level of urine protein excretion.
Conclusions
The antiproteinuric effects of ACE inhibitors and lowering blood pressure are greater in patients with a higher baseline urine protein excretion. The greater beneficial effect of ACE inhibitors on renal disease progression in patients with higher baseline proteinuria can be explained by their greater antiproteinuric effects in these patients. The current level of urine protein excretion is a modifiable risk factor for the progression of non-diabetic renal disease. ACE inhibitors provide greater beneficial effect at all levels of current urine protein excretion.
Keywords:
ACE inhibitors, antihypertensive therapy, urine protein, blood pressure, management of renal disease, angiotensin-converting enzyme, kidney failure
