Transforming growth factc progressive diabetic nephr

enal failure is a common and serious glycosylated protei] complication of longstanding diabetes vasoactive hormon mellitus. Diabetes is now the most common ular hypertension, I cause of end-stage renal failure requiring tors, and cytokines dialysis in the United States, accounting for the pathogenesis c almost 40% of all new dialysis patients (1). (10, 11). Of these, th Moreover, the incidence of renal failure growth factor (TGF caused by diabetes, particularly type II diaing a key role in th betes, is rising dramatically worldwide (2). hypertrophy and ac Compounding the tragedy of the explosive lular matrix in diab growth in the incidence renal failure caused known to have pov by diabetes is the grim reality that the surresulting from bot] vival of patients with renal failure caused by synthesis and inhib: diabetes is much worse than that of patients tion (12). In huma with renal failure resulting from other TGF-P mRNA ane causes. In Germany, for example, Koch et al. nificantly increasec (3) reported a 5-year survival of only 5% tubulointerstitium among patients with type II diabetes underMoreover, short-t( going dialysis. Fortunately, progress is being TGF-3 neutralizing made in our understanding of the pathochemically induced genesis of diabetic renal disease and in our merular enlargeme ability to delay, or even prevent, this devasexpression of gene, tating complication. Two studies appearing matrix components in this issue of PNAS (4, 5) are illustrative of by Ziyadeh et al. (4 this progress. Diabetic nephropathy refers extends these obser to a characteristic set of structural and funcstrongest evidence t tional kidney abnormalities that occur in of TGF-P in the sl patients with diabetes. Although best deabnormalities of di; scribed in patients with type I diabetes (6), Specifically, Ziya similar findings are now known to occur in the effects of long-t the more common type II diabetic patient neutralizing TGF-f (7). Structural abnormalities include hyperfunction and rena trophy of the kidney, an increase in the mice. These mice, t thickness of glomerular basement memhypothalamic leptii branes, accumulation of extracellular matrix obesity caused by ( corrponents in the glomerulus (nodular and tance, and hypergly diffuse glomerulosclerosis), tubular atrothe dbldb mouse phy, and interstitial fibrosis (6, 7). Funcdiabetes mellitus, w tional alterations include an early increase 70-80% of all diab in the glomerular filtration rate with intraure (1). Kidneys fro glornerular hypertension, subsequent proexhibited an increa teinuria, systemic hypertension, and evenpression in glomer tual loss of renal function (8). TGF-3 receptor exi Clinicopathologic studies of diabetic newith nondiabetic c phropathy have established that the extent larly, there was an of matrix accumulation in both the glomerIV collagen al anc uli and the interstitium correlate strongly pression and histol with the degree of renal insufficiency and gial matrix expans proteinuria (9). Accordingly, the factors reFunctional abnorn sponsible for the deposition and accumulaphropathy includet tion of extracellular matrix material within merular filtration r