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Reduction of proteinuria with angiotensin receptor blockers

Nature Clinical Practice Cardiovascular Medicine volume 5, pages S36–S43 (2008)Cite this article

Abstract

Renal pathophysiology is elicited by activation of angiotensin II type 1 (AT1) receptors at all stages of renovascular disease. Angiotensin receptor blockers (ARBs) that specifically block the AT1 receptor offer the potential to prevent or delay progression to end-stage renal disease independently of reductions in blood pressure. Proteinuria—an early and sensitive marker for progressive renal dysfunction—is reduced by ARB use in patients with type 2 diabetic nephropathy and microalbuminuria or macroalbuminuria. Retrospective analysis of data available from early trials has confirmed this finding and has shown that albuminuria reduction is associated with lessening of cardiovascular risk. The ARB telmisartan is equivalent to enalapril in preventing glomerular filtration rate decline, and equivalent to valsartan in reducing proteinuria. Telmisartan is more effective than conventional therapy in lowering the risk of transition to overt nephropathy in hypertensive and normotensive patients. An additive effect has been seen in smaller studies when telmisartan has been added to lisinopril therapy, and high-dose telmisartan reduces albuminuria better than low-dose telmisartan. Similar data were obtained with other ARBs such as candesartan, losartan, valsartan, or irbesartan. These data support the proposition that blockade of the renin–angiotensin system beyond that required for maximum blood pressure reduction provides optimum renal protection.

Key Points

  • Injury to the vascular endothelium and glomerulus can be promoted by an activated renin–angiotensin system and, therefore, inhibition of this system provides renoprotection

  • RAS inhibition reduces proteinuria, which is a key factor in the progression of renal disease

  • Blood pressure control is essential to prevent progression to end-stage renal disease, but because the mechanisms of angiotensin receptor blockers and angiotensin-converting-enzyme inhibitors differ, the effectiveness of the latter might decline over time

  • Combination therapy with angiotensin receptor blockers and angiotensin-converting-enzyme inhibitors seems to produce additional blood-pressure-lowering effects to monotherapy

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Figure 1: The central role of angiotensin II in the pathophysiology of renal disease.
Figure 2: The close relationship between systolic blood pressure and the risk of a renal endpoint in the Irbesartan Diabetic Nephropathy Trial subanalysis.
Figure 3: Changes from baseline in glomerular filtration rate with telmisartan versus enalapril in the DETAIL study.

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Acknowledgements

PAREXEL MMS provided writing assistance, comprising preparation of a draft from slides and audio transcript, preparation of figures and obtaining copyright permissions, proofreading, and reference checking.

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  1. Direktor der Klinik für Nephrologie, Klinikum Lüdenscheid, Paulmannshöher Strasse 14, D-58515 Lüdenscheid, Germany j.galle@klinikum-luedenscheid.de

Authors and Affiliations

  1. J Galle is Head of the Department of Nephrology and Dialysis at the Klinikum Lüdenscheid, and a Fellow of the Deutsche Gesellschaft für Kardiologie, Herz, und Kreislaufforschung and the Deutsche Herzstiftung, Lüdenscheid, Germany.,

    Jan Galle

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Galle, J. Reduction of proteinuria with angiotensin receptor blockers. Nat Rev Cardiol 5 (Suppl 1), S36–S43 (2008). https://doi.org/10.1038/ncpcardio0806

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