Nephron supply is a major determinant of long-term renal allograft outcome in rats

Abstract

The effects of augmenting the nephron supply on indices of allograft injury were assessed in a rat model of 'chronic rejection.' Orthotopic renal allotransplantation into uninephrectomized rats was followed by excision (allograft-alone group) or preservation of the remaining native kidney (allograft-native kidney group) such that the total kidney complement was either the allograft alone, or the allograft plus one retained native kidney. After 18 wk, values for GFR (1.85±0.3 ml/min) and kidney weights (2.3±0.2 g) in allograft-alone rats were far in excess of corresponding values in the allograft of allograft + native kidney rats (0.88±0.1 ml/min and 1.1±0.5 g, respectively). Proteinuria (35±2 mg/d) and allograft glomerulosclerosis (24±8%) also characterized allograft-alone but not allograft + native kidney rats, in whom glomerular structure (allograft glomerulosclerosis, 4±1%; native kidney glomerulosclerosis, 0%) and glomerular functional integrity (proteinuria 7±0.7 mg/d) were well preserved. Thus, the observed allograft protection derived from the presence of a retained recipient native kidney supports the hypothesis that a single renal allograft contains insufficient nephrons to prevent progressive renal injury, implicating nephron supply as a major determinant of long-term allograft outcome.