Nephron Supply Is a Major Determinant of Long-Term Renal Allograft Outcome in Rats

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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. (J. Clin. Invest. 1994. 94:2148-2152.) Key words: chronic rejection. transplantation. kidney diseases. glomerular filtration rate. glomerulosclerosis

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