Renoprotective therapy in patients with nondiabetic nephropathies.
End-stage renal failure (ESRF) represents a major health problem. Early diagnosis and effective measures to slow or to stop renal damage are essential goals for nephrologists to prevent or delay progression to ESRF. Identifying mechanisms of progressive parenchymal injury is instrumental in developing renoprotective strategies. Protein traffic through the glomerular barrier is an important determinant of progression in chronic nephropathies and proteinuria is the best predictor of renal outcome. At the moment, ACE inhibition is the most effective treatment in patients with chronic nondiabetic proteinuric nephropathies, reducing protein traffic, urinary protein excretion rate and progression to ESRF more effectively than conventional treatment. Low sodium diet and/or diuretic treatment may help to increase the antiproteinuric effect of ACE inhibitors by maximally activating the renin-angiotensin system. Intensified blood pressure control, whatever treatment is employed, also enhances the antiproteinuric response to ACE inhibitors. However, since this is not always sufficient to normalise urinary proteins and fully prevent renal damage, additional treatments may be needed in patients poorly or not responding to ACE inhibitors. These may include angiotensin II receptor antagonists, non-dihydropyridine calcium antagonists and perhaps low doses of nonsteroidal anti-inflammatory drugs. Preliminary data on multidrug treatments including these additional antiproteinuric agents are encouraging, but additional studies in larger patient numbers are needed to better define the risk/benefit profile of this innovative approach.
Pisoni
R
R
Department of Kidney Research, Mario Negri Institute for Pharmacological Research, Bergamo, Italy. pisoni@marionegri.it
Ruggenenti
P
P
Remuzzi
G
G
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D002908:Chronic Disease; D004044:Dietary Proteins / Q000008:administration & dosage; D016232:Endothelins / Q000037:antagonists & inhibitors; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D007674:Kidney Diseases / Q000188:drug therapy*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002121:Calcium Channel Blockers; D004044:Dietary Proteins; D016232:Endothelins