Nephron supply is a major determinant of long-term renal allograft outcome in rats.
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 unine-phrectomized 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.
Mackenzie
H S
HS
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Tullius
S G
SG
Heemann
U W
UW
Azuma
H
H
Rennke
H G
HG
Brenner
B M
BM
Tilney
N L
NL
D000818:Animals; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D009399:Nephrons / Q000502:physiology*; D011507:Proteinuria / Q000209:etiology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous