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Management of Glomerular Proteinuria: A Commentary

William A. Wilmer^*, Brad H. Rovin^*, Christopher J. Hebert, Sunil V. Rao, Karen Kumor and Lee A. Hebert^*

*Department of Internal Medicine, The Ohio State University Medical Center, Columbus, Ohio; Case Western Reserve University, Louis Stokes VA Medical Center, Cleveland, Ohio; Department of Medicine, Duke University, Durham, North Carolina; and Alexion Pharmaceuticals, Inc., Cheshire, Connecticut.

Correspondence to Dr. Lee A. Hebert, The Ohio State University Medical Center, 1654 Upham Drive, Columbus, OH 43210-1250. Phone: 614-293-4997; Fax: 614-293-3073; E-mail: hebert.1{at}osu.edu

ABSTRACT. It is widely accepted that proteinuria reduction is an appropriate therapeutic goal in chronic proteinuric kidney disease. Based on large randomized controlled clinical trials (RCT), ACE inhibitor (ACEI) and angiotensin receptor blocker (ARB) therapy have emerged as the most important antiproteinuric and renal protective interventions. However, there are numerous other interventions that have been shown to be antiproteinuric and, therefore, likely to be renoprotective. Unfortunately testing each of these antiproteinuric therapies in RCT is not feasible. The nephrologist has two choices: restrict antiproteinuric therapies to those shown to be effective in RCT or expand the use of antiproteinuric therapies to include those that, although unproven, are plausibly effective and prudent to use. The goal of this work is to provide the documentation needed for the nephrologist to choose between these strategies. This work describes 25 separate interventions that are either antiproteinuric or may block injurious mechanisms of proteinuria. Each intervention is assigned a level of recommendation (Level 1 is the highest; Level 3 is the lowest) according to the strength of the evidence supporting its antiproteinuric and renoprotective efficacy. Pathophysiologic mechanisms possibly involved are also discussed. The number of interventions at each level of recommendation are: Level 1, n = 7; Level 2, n = 9; Level 3, n = 9. Our experience indicates that we can achieve in most patients the majority of Level 1 and many of the Level 2 and 3 recommendations. We suggest that, until better information becomes available, a broad-based, multiple-risk factor intervention to reduce proteinuria can be justified in those with progressive nephropathies. This work is intended primarily for clinical nephrologists; therefore, each antiproteinuria intervention is described in practical detail.

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