on August 9, 2004
Circulation. 2004
Published online before print August 9, 2004, doi: 10.1161/01.CIR.0000139860.33974.28
Published online before print August 9, 2004, doi: 10.1161/01.CIR.0000139860.33974.28
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Submitted on July 22, 2003
From the Department of Clinical Pharmacology, Groningen University Medical Center, the Netherlands (D.d.Z.); Mario Negri Institute for Pharmacological Research, Bergamo, Italy (G.R.); Steno Diabetes Center Gentofte and Faculty of Health Science, Aarhus University, Denmark (H.-H.P.); Merck Research Laboratories, Merck & Co, Inc, Whitehouse Station, NJ (W.F.K., Z.Z., S. Shahinfar, S. Snapinn); Baker Medical Research Institute, Melbourne, Australia (M.E.C.); Department of Medicine, University of Texas, Medical Branch, Galveston (W.E.M.); and Department of Medicine, Renal Division, Brigham and Women’s Hospital and Harvard School of Medicine, Boston, Mass (B.M.B.). * To whom correspondence should be addressed. E-mail: d.de.zeeuw{at}med.rug.nl.
Background--Albuminuria is an established risk marker for both cardiovascular and renal outcomes. Albuminuria can be reduced with drugs that block the renin-angiotensin system (RAS). We questioned whether the short-term drug-induced change in albuminuria would predict the long-term cardioprotective efficacy of RAS intervention. Methods and Results--We analyzed data from Reduction in Endpoints in Non-insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL), a double-blind, randomized trial in 1513 type 2 diabetic patients with nephropathy, focusing on the relationship between the prespecified cardiovascular end point (composite) or hospitalization for heart failure and baseline or reduction in albuminuria. Patients with high baseline albuminuria ( Conclusions--Albuminuria is an important factor predicting cardiovascular risk in patients with type 2 diabetic nephropathy. Reducing albuminuria in the first 6 months appears to afford cardiovascular protection in these patients.
Revised on April 20, 2004
Accepted on April 22, 2004
Albuminuria, a Therapeutic Target for Cardiovascular Protection in Type 2 Diabetic Patients With Nephropathy
Dick de Zeeuw MD, PhD*,
3 g/g creatinine) had a 1.92-fold (95% CI, 1.54 to 2.38) higher risk for the cardiovascular end point and a 2.70-fold (95% CI, 1.94 to 3.75) higher risk for heart failure compared with patients with low albuminuria (<1.5 g/g). Among all available baseline risk markers, albuminuria was the strongest predictor of cardiovascular outcome. The association between albuminuria and cardiovascular outcome was driven by those patients who also had a renal event. Modeling of the initial 6-month change in risk parameters showed that albuminuria reduction was the only predictor for cardiovascular outcome: 18% reduction in cardiovascular risk for every 50% reduction in albuminuria and a 27% reduction in heart failure risk for every 50% reduction in albuminuria.
Key words: proteinuria • albuminuria • cardiovascular disease • angiotensin • diabetes
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R. Agarwal and M. J. Andersen Correlates of Systolic Hypertension in Patients With Chronic Kidney Disease Hypertension, September 1, 2005; 46(3): 514 - 520. [Abstract] [Full Text] [PDF]
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J. Arnlov, J. C. Evans, J. B. Meigs, T. J. Wang, C. S. Fox, D. Levy, E. J. Benjamin, R. B. D'Agostino, and R. S. Vasan Low-Grade Albuminuria and Incidence of Cardiovascular Disease Events in Nonhypertensive and Nondiabetic Individuals: The Framingham Heart Study Circulation, August 16, 2005; 112(7): 969 - 975. [Abstract] [Full Text] [PDF]
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C. W, Y. PX, L. BM, C. RD, M. DL, M. RH, I. H, O. MH, W. K, B.-J. K, et al. Anorexia and Cachexia in Renal Failure--Is Leptin the Culprit?: Role of Leptin and Melanocortin Signaling in Uremia-Associated Cachexia. J Clin Invest 115: 1659-1665, 2005 J. Am. Soc. Nephrol., August 1, 2005; 16(8): 2245 - 2250. [Full Text] [PDF]
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D. de Zeeuw Albuminuria, Just a Marker for Cardiovascular Disease, Or Is It More? J. Am. Soc. Nephrol., July 1, 2005; 16(7): 1883 - 1885. [Full Text] [PDF]
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J. Redon Urinary Albumin Excretion: Lowering the Threshold of Risk in Hypertension Hypertension, July 1, 2005; 46(1): 19 - 20. [Full Text] [PDF]
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F. Togel, Z. Hu, K. Weiss, J. Isaac, C. Lange, C. Westenfelder, T. Stasko, M.D. Brown, J.A. Carucci, S. Euvrard, et al. Amelioration of Acute Renal Failure by Stem Cell Therapy--Paracrine Secretion Versus Transdifferentiation into Resident Cells: Administered Mesenchymal Stem Cells Protect against Ischemic Acute Renal Failure through Differentiation-Independent Mechanisms. Am J Physiol Renal Physiol E-pub February 15, 2005 J. Am. Soc. Nephrol., May 1, 2005; 16(5): 1153 - 1163. [Full Text] [PDF]
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 Other articles noted Evid. Based Med., April 1, 2005; 10(2): 63 - 64. [Full Text] [PDF]
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A. Smith, J. Karalliedde, L. De Angelis, D. Goldsmith, and G. Viberti Aortic Pulse Wave Velocity and Albuminuria in Patients with Type 2 Diabetes J. Am. Soc. Nephrol., April 1, 2005; 16(4): 1069 - 1075. [Abstract] [Full Text] [PDF]
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M. R. Weir Reduction in Microalbuminuria: A Biomeasure of Therapeutic Success? Hypertension, February 1, 2005; 45(2): 181 - 182. [Full Text] [PDF]
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H. Ibsen, M. H. Olsen, K. Wachtell, K. Borch-Johnsen, L. H. Lindholm, C. E. Mogensen, B. Dahlof, R. B. Devereux, U. de Faire, F. Fyhrquist, et al. Reduction in Albuminuria Translates to Reduction in Cardiovascular Events in Hypertensive Patients: Losartan Intervention for Endpoint Reduction in Hypertension Study Hypertension, February 1, 2005; 45(2): 198 - 202. [Abstract] [Full Text] [PDF]
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W. E. Mitch Treating Diabetic Nephropathy -- Are There Only Economic Issues? N. Engl. J. Med., November 4, 2004; 351(19): 1934 - 1936. [Full Text] [PDF]
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