Bilateral native nephrectomy improves renal isograft function in rats

Bilateral native nephrectomy has been suggested to improve renal allograft survival in man. This effect may be most prominent in patients experiencing acute tubular necrosis following transplantation. Thus, native kidneys may alter the course of ischemic acute tubular necrosis in the transplanted kidney. In the present studies, we utilized an experimental model of syngeneic transplantation in which rejection does not occur. We studied Lewis rat renal isografts transplanted into littermates following sham, unilateral or bilateral native nephrectomy. In a fourth group of rats, we evaluated the importance of native kidney excretory function by studying isografts transplanted into littermates with bilaterally obstructed native kidneys. Renal blood flow and excretory function were measured in vivo, eight days following transplantation. Renal excretory function of isografts transplanted into animals following bilateral native nephrectomy was similar to normal nontransplanted Lewis kidneys. The presence of either one or both functioning native kidneys significantly reduced isograft inulin clearance, PAH clearance, and blood flow. However, when isografts were transplanted into Lewis rats with bilaterally obstructed native kidneys, renal isograft inulin clearance and blood flow were not significantly impaired. Nontransplanted kidneys demonstrated 'functional hypertrophy' following contralateral nephrectomy, with glomerular filtration rate and renal blood flow increasing by approximately 50%. In contrast, isograft glomerular filtration rate in animals following bilateral native nephrectomy was equivalent to that of single kidneys from normal animals with both kidneys in situ. However, renal blood flow of isografts from these animals increased to the same level as nontransplanted Lewis kidneys following contralateral nephrectomy. Histological examination of isografts from animals with functioning native kidneys in situ demonstrated extensive disruption of normal renal architecture with tubular and interstitial injury. This was in marked contrast to the appearance of Lewis-Brown Norway allografts, to isografts from animals following bilateral native nephrectomy, and to isografts from animals with bilaterally obstructed native kidneys. In Lewis-Brown Norway allografts, there was evidence of rejection with active inflammatory cell infiltration, arteriolitis and venulitis. In isografts from animals following bilateral native nephrectomy or with bilaterally obstructed native kidneys, renal architecture was normal. Thus, the detrimental effect of native kidneys on isograft function may be related to impaired recovery from ischemia or potentiation of ischemic injury which occurs during the transplantation procedure.