Renal mass as a determinant of late allograft outcome: insights from experimental studies in rats

Experimental studies of renal mass augmentation were conducted in the Fisher-->Lewis rat model of late renal allograft failure to assess the injury attributable to inadequate nephron supply in single allografts. Marked proteinuria, glomerulosclerosis and cellular infiltration developed in bilaterally nephrectomized recipients of single allografts at 16 to 20 weeks. By contrast, recipients with two kidney showed markedly reduced indices of allograft injury, irrespective of whether the second kidney was native or transplanted. Micropuncture whether the second kidney was native or transplanted. Micropuncture study of solitary allografts revealed glomerular hyperfiltration and elevated glomerular capillary pressure with marked inter-nephron variation despite normal systemic arterial pressure. In the two-kidney groups, single-nephron GFR and glomerular capillary pressures were essentially normal. These findings provide unambiguous evidence that the cycle of progressive nephron loss characteristic of extensive renal mass ablation operates in single allografts and contributes significantly to injury. The magnitude of allograft protection obtained by augmenting renal mass attests to the importance of nephron supply as a determinant of injury in this model. We conclude that mass-related injury processes may play a potentially major and underappreciated role in the pathogenesis of late renal allograft failure.