PHYSIOLOGICAL AND STRUCTURAL RESPONSES TO CHRONIC EXPERIMENTAL RENAL-ALLOGRAFT INJURY

Chronic rejection necessitates a return to dialysis or retransplantati on for a significant number of patients with renal allografts. Althoug h alloresponses between donor organ and recipient importantly determin e this process, the detailed immunologic processes and organ physiolog y of chronic rejection are unclear; in consequence its mechanism and t herapy are uncertain. A model of chronic rejection in the rat was used to examine several facets of this process. Fisher-to-Lewis (F-L), all ogeneic, and Lewis-to-Lewis (L-L), syngeneic, renal transplants were p erformed in nephrectomized recipients. All rats were treated with cycl osporin A (5 mg.kg(-1).day(-1)) for 10 days from the time of grafting. At 6 wk, allogeneically grafted animals had a higher protein excretio n rate (F-L, 47 +/- 30 mg/day; L-L, 17 +/- 6 mg/day; P < 0.05) and an increase in glomerular capillary pressure (F-L, 69 +/- 5 mmHg; L-L, 58 +/- 8 mmHg; P < 0.05) and fractional cortical interstitial volume (F- L, 29.8 +/- 4.3%; L-L, 19.5 +/- 4.0%; P < 0.01). This model of chronic rejection is characterized by glomerular capillary hypertension, prot einuria, and cortical interstitial expansion. Because these findings a re also present in other models of chronic renal injury, mechanisms in addition to alloresponses may operate in chronic rejection.