Protein overload activates proximal tubular cells to release vasoactive and inflammatory mediators

Chronic renal diseases with highly enhanced glomerular permeability to prot eins are accompanied by tubulointerstitial inflammation and scarring and pr ogression to renal failure. As a consequence of increased glomerular permea bility, proteins filtered through the glomerular capillary in excessive amo unt: have intrinsic renal toxicity at least partially linked to their accum ulation in the proximal tubular cell cytoplasm during the process of reabso rption along the nephron. Experimental evidence is available showing that p rotein overload per se activates proximal tubular epithelial cells in cultu re to upregulate genes encoding for endothelin, chemokines and cytokines, T hese vasoactive and inflammatory substances, formed in excessive quantities by the tubular cells, are released mainly into the basolateral compartment , a pattern of secretion that in the kidney would favor recruitment and act ivation of inflammatory cells into the renal interstitium and fibrogenic re action leading to renal scarring. Copyright (C) 1999 S. Karger AG, Basel.