RENAL MASS AS A DETERMINANT OF LATE ALLOGRAFT OUTCOME - INSIGHTS FROMEXPERIMENTAL 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 dev eloped in bilaterally nephrectomized recipients of single allografts a t 16 to 20 weeks. By contrast, recipients with two kidneys showed mark edly reduced indices of allograft injury, irrespective of whether the second kidney was native or transplanted. Micropuncture study of solit ary allografts revealed glomerular hyperfiltration and elevated glomer ular capillary pressure with marked inter-nephron variation despite no rmal systemic arterial pressure. In the two-kidney groups, single-neph ron GFR and glomerular capillary pressures were essentially normal. Th ese findings provide unambiguous evidence that the cycle of progressiv e nephron loss characteristic of extensive renal mass ablation operate s in single allografts and contributes significantly to injury. The ma gnitude of allograft protection obtained by augmenting renal mass atte sts 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 lat e renal allograft failure.