Clinical observations suggest that recipients of multiorgan transplants from the same donor can have disparate immunological reactions to each organ. We studied this phenomenon in 36 diabetic ...(streptozotocin-induced), bilaterally nephrectomized, immunosuppressed (cyclosporine, azathioprine, prednisone) pig recipients of simultaneous (same donor) pancreas (bladder drained) and kidney allografts by grading the histological intensity of rejection in biopsies of each organ at defined intervals 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, moderate, 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%, 29%, 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 organs (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 > or = 2 grades) and at 2 weeks (n = 7) in 57% (29% by 1 and 29% by > or = 2 grades). The inability to use the severity of interstitial rejection in one organ to predict the findings in the other is exemplified by the fact that for the two pancreases without interstitial rejection at one week, the corresponding kidney showed moderate or severe rejection, and for the 1 kidney without rejection the corresponding pancreas showed moderate rejection. Vascular rejection grades (absent, mild, moderate, severe) also showed a similar distribution for 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 > or = 0.64). However, the grading of vascular rejection in organ pairs was dyssynchronous in 54% at 1 week (n = 22) and 29% at 2 weeks (n = 7). No vascular rejection in the pancreas with rejection in the kidney was seen in 5 pairs at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kidney with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at 2 weeks (29%).
Clinically, the incidence of reversible renal allograft rejection episodes appears to be higher in recipients of simultaneous pancreas/kidney (SPK) than of kidney transplantation alone (KTA); ...conversely, the rate of irreversible pancreas allograft rejection appears to be higher in pancreas transplant alone (PTA) than SPK recipients. Clinical/histological correlation of graft rejection in these three groups has not been precise. Therefore, we studied the incidence and histological severity of the rejection process in a large animal (pig) model of SPK (n = 36), PTA (n = 31), and KTA (n = 36) allotransplantation. SPK and PTA recipients were made diabetic pretransplant by streptozotocin (150 mg/kg). Pancreas graft exocrine secretions were bladder-drained via a duodenocystostomy for urine amylase (UA) monitoring; endocrine function was monitored by plasma glucose (PG) levels. SPK and KTA recipients underwent native nephrectomy, and renal allograft function was monitored by serum creatinine (CR). Cyclosporine, azathioprine, and prednisone were given in tapering doses from the time of transplantation. Grafts were biopsied weekly to grade histologic severity of interstitial and vascular rejection on light microscopy (LM) and for intensity of T cell infiltration on immunofluorescence. Pancreas graft exocrine function (UA above pretransplant baseline), present in 62% of PTA and 68% of SPK recipients at one week, persisted in only 7% of PTA vs. 64% of SPK pigs at 2 weeks (P = 0.0004). Likewise, pancreas graft endocrine function (PG < 200 mg/dl off insulin) was sustained longer in SPK than PTA recipients (100% vs. 84% at 1 and 91% vs. 27% at 2 weeks; P = 0.0006). However, renal allograft functional survival (serum creatinine < 3.0 mg/dl) was not significantly different (P = 0.471) between SPK and KTA recipients (36% vs. 30% at 1 and 23% vs. 13% at 2 weeks). Graft functional parameters partially correlated with biopsy observations. Pancreas allograft biopsies showed a significantly (P = 0.03 at 1 and P = 0.05 at 2 weeks) lower incidence of moderate/severe interstitial rejection in SPK than PTA recipients (67% vs. 95% at 1 and 57% vs. 92% at 2 weeks); rejection was absent in 8% of SPK and in no PTA biopsies at 1 week. Vascular rejection was moderate/severe in significantly fewer (P = 0.0013 at 1 and P = 0.023 at 2 weeks) SPK than PTA pancreas grafts (13% vs. 37% at 1 and 14% vs. 38% at 2 weeks).
Clinical observations suggest that recipients of multiorgan transplants from the same donor can have disparate immunological reactions to each organ. We studied this phenomenon in 36 diabetic ...(streptozotocin-induced), bilaterally nephrectomized immunosuppressed (cyclosporine, azathioprine, prednisone) pig recipients of simultaneous (same donor) pancreas (bladder drained) and kidney allografts by grading the histological intensity of rejection in biopsies of each organ at defined intervals 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, moderate, and severe in, respectively, 8%, 25%, 42%, and 5% of pancreas vs. 4%, 12%, 27%, and 50% of kidney biopsies at 1 week; and 0%, 43%, 29%, 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 organs (P > 0.1), the grade of rejection for each pair at 1 week (n = 24) was discordant in 75% (41% differed by one and 35% by > or = 2 grades) and at 2 weeks (n = 7) in 57% (29% by 1 and 29% by > or = 2 grades). The inability to use the severity of interstitial rejection in one organ to predict the findings in the other is exemplified by the fact that for the two pancreases without interstitial rejection at one week, the corresponding kidney showed moderate or severe rejection, and for the 1 kidney without rejection the corresponding pancreas showed moderate rejection. Vascular rejection grades (absent, mild, moderate, severe) also showed a similar distribution for the pancreas (57%, 30%, 9%, 4%) vs. kidney (56%, 30%, 0%, 13%) 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 > or = 0.64). However, the grading of vascular rejection in organ pairs was dyssynchronous in 51% at 1 week (n = 22) and 29% at 2 weeks (n = 7). No vascular rejection in the pancreas with rejection in the kidney was seen in 5 pairs at 1 week (23%) and 0 at 2 weeks (0%), while no rejection in the kidney with rejection in the pancreas was seen in 5 pairs at 1 week (23%) and 2 pairs at 2 weeks (29%).
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