Author(s): Remuzzi G, Ruggenenti P, Benigni A
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Abstract Animal and human proteinuric glomerulopathies evolve to terminal renal failure by a process leading to progressive parenchymal damage, which appears to be relatively independent of the initial insult. Despite the fact that the mechanism(s) leading to renal disease progression has been only partially clarified, several studies have found that the amount of urinary proteins (taken to reflect the degree of protein trafficking through the glomerular capillary) correlated with the tendency of a given disease to progress more than the underlying renal pathology. On the other hand, dietary protein restriction and ACE inhibitors were capable of limiting the progressive decline in GFR to the extent that they could effectively lower the urinary protein excretion rate. A constant feature of proteinuric nephritis is also the concomitant presence of tubulointerstitial inflammation. So far it was not clear if this is a reaction to the ischemic obliteration of peritubular capillaries that follows glomerular obsolescence or whether albumin and other proteins that accumulated in the urinary space are indeed instrumental for the formation of the interstitial inflammatory reaction. In recent years several studies have convincingly documented that excessive and sustained protein trafficking could have an intrinsic renal toxicity. Here we have reviewed the abundant evidence in the literature that the process of reabsorption of filtered proteins activates the proximal tubular epithelium. Biochemical events associated with tubular cell activation in response to protein stress include up-regulation of inflammatory and vasoactive genes such as MCP-1 and endothelins. The corresponding molecules formed in an excessive amount by renal tubuli are secreted toward the basolateral compartment of the cell and give rise to an inflammatory reaction that in most forms of glomerulonephritis consistently precede renal scarring.
This article was published in Kidney Int
and referenced in Journal of Nephrology & Therapeutics