NEPHRON MASS MODULATES THE HEMODYNAMIC, CELLULAR, AND MOLECULAR RESPONSE OF THE RAT RENAL-ALLOGRAFT

Functioning nephron mass has recently been implicated as a risk factor for development of chronic ''rejection'' of kidney allografts, Reduct ions in nephron number below 50% may induce glomerular hypertension an d hyperfiltration in surviving units, which in turn lead to graft inju ry, In the present study, which extends and amplifies our previous inv estigations, cellular and molecular characteristics of single allograf ts from F344 donors in bilaterally nephrectomized LEW recipients, our standard experimental model of chronic renal allograft dysfunction, we re compared with allografts from recipients where total renal mass was reduced (by ligating branches of the graft renal artery) or restored to normal levels by transplanting or retaining a second kidney. Our fi ndings in this study confirm that progressive proteinuria and structur al injury in recipients of single allografts were accentuated in graft s with reduced mass but virtually absent in rats with increased kidney mass, A striking observation was that patterns of cell surface molecu le expression, cellular infiltration, and expression of all T cell- an d macrophage-associated products studied were all markedly modulated b y changes in renal mass, Moreover, several molecules that are up-regul ated before evidence of graft injury are down-regulated by providing i ncreased renal mass, These data show that the quantity of functioning renal mass is not only an important independent determinant of the tem po and intensity of chronic renal allograft failure, but also a potent modulator of fundamental cellular and molecular components of a compl ex process, This phenomenon involves antigen-dependent and antigen-ind ependent elements that ultimately result in chronic allograft failure.