Physiological and structural responses to chronic experimental renal allograft injury
Junaid, A.; Kren, S.M.; Rosenberg, M.E.; Nath, K.A.; Hostetter, T.H.
American Journal of Physiology 267(6 Pt 2): F1102-F1106
1994
ISSN/ISBN: 0002-9513 PMID: 7810697 Document Number: 429126
Chronic rejection necessitates a return to dialysis or retransplantation for a significant number of patients with renal allografts. Although alloresponses between donor organ and recipient importantly determine this process, the detailed immunologic processes and organ physiology of chronic rejection are unclear; in consequence its mechanism and therapy are uncertain. A model of chronic rejection in the rat was used to examine several facets of this process. Fisher-to-Lewis (F-L), allogeneic, and Lewis-to-Lewis (L-L), syngeneic, renal transplants were performed in nephrectomized recipients. All rats were treated with cyclosporin A (5 mg cntdot kg-1 cntdot day-1) for 10 days from the time of grafting. At 6 wk, allogeneically grafted animals had a higher protein excretion rate (F-L, 47 cntdot 30 mg/day; L-L, 17 +- 6 mg/day; P lt 0.05) and an increase in glomerular capillary pressure (F-L, 69 +- 5 mmHg; L-L, 58 cntdot 8 mmHg; P lt 0.05) and fractional cortical interstitial volume (F-L, 29.8 +- 4.3%; L-L, 19.5 +- 4.0%; P lt 0.01). This model of chronic rejection is characterized by glomerular capillary hypertension, proteinuria, and cortical interstitial expansion. Because these findings are also present in other models of chronic renal injury, mechanisms in addition to alloresponses may operate in chronic rejection.