Effect of proteinuria on renal interstitium: Effect of products of nitrogen metabolism

Tubulointerstitial disease is an invariant finding in proteinuric renal disease regardless of the underlying disease or the compartment in which the disease originates. Such histologic changes are functionally significant in that scores of such injury rather than glomerular histologic injury correlate with decrements in GFR. Proteinuria, the consequence of a loss of glomerular permselectivity incurred by glomerular diseases, also provides an index of renal functional decline. This review provides evidence that proteins leaked into the urinary space may directly or indirectly provoke tubulointerstitial injury, a linkage that may underlie the functional significance of proteinuria and tubulointerstitial disease. This review also highlights two products of nitrogen metabolism, ammonia and nitric oxide, in the pathogenesis of tubulointerstitial disease.