DIFFERENCES IN REJECTION GRADING AFTER SIMULTANEOUS PANCREAS AND KIDNEY-TRANSPLANTATION IN PIGS (DECEMBER 1993)

Clinical observations suggest that recipients of multiorgan transplant s from the same donor can have disparate immunological reactions to ea ch organ. We studied this phenomenon in 36 diabetic (streptozotocin-in duced), bilaterally nephrectomized, immuno-suppressed (cyclosporine, a zathioprine, prednisone) pig recipients of simultaneous (same donor) p ancreas (bladder drained) and kidney allografts by grading the histolo gical intensity of rejection in biopsies of each organ at defined inte rvals posttransplant. Graft function was monitored by plasma glucose ( PG) and urine amylase (UA) for the pancreas and serum creatinine (Cr) for the kidney. Interstitial rejection was graded as absent, mild, mod erate, and severe in, respectively, 8%, 25%, 42%, and 25% of pancreas vs. 4%, 12%, 27%, and 57% of kidney biopsies at 1 week; and 0%, 43%, 2 9%, and 29% of pancreases vs. 10%, 0%, 30%, and 60% of kidneys at two weeks. Although the distribution of grades was similar in the two orga ns (P>0.1), the grade of rejection for each pair at 1 week (n=24) was discordant in 75% (42% differed by one and 33% by greater than or equa l to 2 grades) and at 2 weeks (n=7) in 57% (29% by 1 and 29% by greate r than or equal to 2 grades). The inability to use the severity of int erstitial rejection in one organ to predict the findings in the other is exemplified by the fact that for the two pancreases without interst itial rejection at one week, the corresponding kidney showed. moderate or severe rejection, and for the 1 kidney without rejection the corre sponding pancreas showed moderate rejection. Vascular rejection grades (absent, mild, moderate, severe) also showed a similar distribution f or the pancreas (57%, 30%, 9%, 4%) vs. kidney (50%, 38%, 0%, 12%) at 1 week, and at 2 weeks (57%, 29%, 0%, and 14% for the pancreas vs. 78%, 11%, 0%, and 11 for the kidney) (P greater than or equal to 0.64). Ho wever, the grading of vascular rejection in organ pairs was dyssynchro nous in 54% at 1 week (n=22) and 29% at 2 weeks (n=7). No vascular rej ection in the pancreas with rejection in the kidney was seen in 5 pair s at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kid ney with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at 2 weeks (29%). Clinical evidence of rejection at 1 wee k was present in 64% of kidney (creatinine > 3 mg/dl) and 32% of exocr ine pancreas (UA decreased 50%) and 0% of endocrine pancreas (PG > 200 mg/dl) grafts, and at 2 weeks in 77% of kidney, 36% of exocrine, and 9% of endocrine pancreas grafts. Neither urine amylase nor plasma gluc ose levels correlated with interstitial biopsy rejection grades at 1 o r 2 weeks (P greater than or equal to 0.19). Interstitial biopsy rejec tion grades also did not correlate with serum creatinine levels at 1 w eek (P=0.36), but did at 2 weeks (P=0.009). Clinical dysfunction from rejection tends to occur more rapidly in the kidney than the pancreas following combined allografting, but histologically severe rejection c an be present in one organ while the second remains unaffected. The se verity of histological rejection usually varies between organs of a pa ir, but there is no consistent pattern in whether the kidney or pancre as is more or less afflicted. Thus, dyssynchronous rejection is unlike ly due to inherent differences in alloantigen expression between the t wo organs, and further studies are needed to determine the factors tha t predispose to amplification of the alloimmune response to a greater degree in one organ than the other of a pair.