Glomerular preload and afterload reduction as a tool to lower urinary protein leakage: will such treatments also help to improve renal function outcome?
It has been well documented that different therapeutic strategies, including angiotensin-converting enzyme (ACE) inhibitors, nonsteroidal anti-inflammatory drugs, and dietary protein restriction, lower urinary protein excretion in patients with diabetic and non-diabetic nephropathy. Experimental evidence suggests that this antiproteinuric effect is, at least in part, related to a reduction in the glomerular capillary hydraulic pressure. ACE inhibitors appear to achieve this reduction in glomerular capillary pressure, mainly through a fall in postglomerular arteriolar resistance, whereas dietary protein restriction and non-steroidal antiinflammatory drugs appear to invoke the response predominantly through an increase in preglomerular resistance. This leads to the suggestion that both "glomerular preload reduction" (afferent vasoconstriction) and "glomerular afterload reduction" (efferent vasodilation) will result in an anti-proteinuric response. Interestingly, these same therapeutic regimens, particularly the ACE inhibitors and low-protein diets, have been proven to prevent progressive glomerulosclerosis in animal models. This concept of influencing glomerular hemodynamics both at the afferent and efferent arteriolar level may open new perspectives in the treatment of patients with renal protein loss and renal failure. At present, however, it is too early to conclude whether the fall in proteinuria induced by these treatments will also contribute to a better renal survival of these patients.
de Jong
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PE
Anderson
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S
de Zeeuw
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D
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D003928:Diabetic Nephropathies / Q000503:physiopathology / Q000628:therapy; D004044:Dietary Proteins / Q000008:administration & dosage; D006801:Humans; D007678:Kidney Glomerulus / Q000187:drug effects / Q000503:physiopathology; D009404:Nephrotic Syndrome / Q000503:physiopathology / Q000628:therapy; D011507:Proteinuria / Q000503:physiopathology / Q000628:therapy*
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004044:Dietary Proteins