Therapeutic measures in proteinuric nephropathy.
The level of proteinuria is one of the most important risk factors for progressive renal function loss in renal diseases. Any therapeutic measure that reduces proteinuria will slow or halt the progression of proteinuric nephropathies. Blockade of the renin-angiotensin-aldosterone system (RAAS) with angiotensin-converting enzyme (ACE) inhibitors or AT1-receptor antagonists (ARA) is currently the most powerful available antiproteinuric treatment. Recent investigations point out that blockade of RAAS at other levels (e.g., aldosterone or renin antagonists) could also induce a significant decrease in proteinuria. Because angiotensin II is also generated from angiotensin I by enzymes other than ACE, ARA would provide a more effective blockade of angiotensin II; however, ACE inhibition increases plasma levels of substances such as bradykinin and N-acetyl-seryl-aspartyl-lysyl-proline, which have strong antifibrotic properties. These differential effects of ACE inhibitors and ARA are the rationale for combined administration of both agents, which in clinical studies has demonstrated a significantly higher antiproteinuric and renoprotective effect than by either drug alone. Salt and protein restriction, as well as cautious use of diuretics, can also increase the antiproteinuric effect of RAAS blockade. Treatment with statins or other lipid-lowering agents leads to reduction in proteinuria levels, as some meta-analyses have demonstrated. Smoking is associated with an increased risk for the appearance of proteinuria, so cessation of smoking should be mandatory in proteinuric renal diseases. Recent studies have highlighted an epidemic increase of obesity-related proteinuric glomerulopathies; weight loss is effective not only in this condition, but also in overweight patients with proteinuric nephropathies of other etiologies.
Praga
Manuel
M
Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain. mpragat@senefro.org
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D018450:Disease Progression; D004359:Drug Therapy, Combination; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000503:physiopathology; D007333:Insulin Resistance; D007674:Kidney Diseases / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D009395:Nephritis, Interstitial / Q000503:physiopathology; D011507:Proteinuria / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D051437:Renal Insufficiency / Q000503:physiopathology; D012083:Renin / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000502:physiology; D012307:Risk Factors; D016540:Smoking Cessation; D015431:Weight Loss; D000092502:Renin Inhibitors
D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000451:Mineralocorticoid Receptor Antagonists; D012083:Renin; D000092502:Renin Inhibitors