The relationship between reduced functioning kidney mass and chronic rejection in rats.
Interest has recently increased in the role of alloantigen-independent factors in chronic rejection. In this context, we examined the long-term effects of reduced functioning kidney mass in a F344-->LEW allograft (A) model. Animals were divided into three groups depending upon the amount of retained kidney. Renal arterial branches in the hilus were ligated so that one-third or two-thirds of the graft remained viable (1/3 and 2/3 groups, respectively); organs were left intact in the third (3/3) group. Urine protein concentrations were determined 4, 6, 8 and 10 weeks after engraftment and organs (five/group/time) were harvested and examined morphologically and immunohistologically. Proteinuria increased progressively in all 1/3, 2/3 and 3/3A animals, but faster in those with reduced kidney mass. This functional decline correlated well with increasing numbers of macrophages followed by interstitial fibrosis and glomerular sclerosis, which had become prominent by week 6 in group 1/3A and by 8 weeks in groups 2/3A and 1/3I (I, isografted), with animals beginning to die. IL-1, IL-6 and TNF production correlated well with the location and number of macrophages in all groups. These results suggest that kidney mass exerts a significant alloantigen-independent influence on chronic rejection. Allogenicity of the graft accelerates and amplifies the process.
Surgical Research Laboratory, Harvard Medical School, Boston, MA 02115, USA.
U W
UW
Heemann
S G
SG
Tullius
H
H
Azuma
N L
NL
Tilney
D000818:Animals; D002908:Chronic Disease; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000503:physiopathology*; D006085:Graft Survival; D007375:Interleukin-1 / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D011507:Proteinuria; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D012077:Renal Artery / Q000502:physiology; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha