Simultaneous administration of adjuvant donor bone marrow in pancreas transplant recipients. (9/501)

OBJECTIVE: The effect of donor bone marrow was evaluated for its potentially favorable effect in the authors' simultaneous pancreas/kidney transplant program. METHODS: From July 1994 to January 1999, 177 pancreas transplants were performed, 151 of which were simultaneous pancreas/kidney transplants. All patients received tacrolimus, mycophenolate mofetil, and steroids for immunosuppression (azathioprine was used in the first year of the program). Fifty-three simultaneous pancreas/kidney transplant recipients received perioperative unmodified donor bone marrow, 3 to 6 x 10(8) cells/kg. RESULTS: Overall actuarial survival rates at 1 and 3 years were 98% and 95% (patient), 95% and 87% (kidney), and 86% and 80% (pancreas), respectively. In the adjuvant bone marrow group, 1- and 3-year survival rates were 96% and 91 % (patient), 95% and 87% (kidney), and 83% and 83% (pancreas), respectively. For 98 recipients who did not receive bone marrow, survival rates at 1 and 3 years were 100% and 98% (patient), 96% and 86% (kidney), and 87% and 79% (pancreas), respectively. No pancreas allografts were lost after 3 months in bone marrow recipients, and seven in the non-bone marrow recipients were lost to rejection at 0.7, 6.7, 8.8, 14.6, 24.1, 24.3, and 25.5 months. Twenty-two percent of bone marrow patients were steroid-free at 1 year, 45% at 2 years, and 67% at 3 years. Nineteen percent of the non-bone marrow recipients were steroid-free at 1 year, 38% at 2 years, and 45% (p = 0.02) at 3 years. The mean acute cellular rejection rate was 0.94+/-1.1 in the bone marrow group and 1.57+/-1.3 (p = 0.003) in the non-bone marrow group (includes borderline rejection and multiple rejections). The level of donor cell chimerism in the peripheral blood of bone marrow patients was at least two logs higher than in controls. CONCLUSION: In this series, which represents the largest experience with adjuvant bone marrow infusion in pancreas recipients, there was a higher steroid withdrawal rate (p = 0.02), fewer rejection episodes, and no pancreas graft loss after 3 months in bone marrow recipients compared with contemporaneous controls. All pancreas allografts lost to chronic rejection (n = 6) were in the non-bone marrow group. Donor bone marrow administered around the time of surgery may have a protective effect in pancreas transplantation.  (+info)

CD4+ CD45RB low-density cells from untreated mice prevent acute allograft rejection. (10/501)

In the absence of therapy that suppresses the action of the immune system, the immune response to transplantation Ags results in rapid rejection of the transplant. The most successful mechanism so far described that achieves organ-specific immunological tolerance is that which controls peripheral tolerance to self-tissue. Until now, no similarities have been documented between the peripheral response to self-Ags and the response to transplantation Ags. CD4+ cells that express a high density of CD45RB (in the mouse) and CD45RC (in the rat) on their surface have been shown to cause a number of autoimmune disorders. In contrast, autoimmunity caused by the CD45RB high-density cells is inhibited by CD4+ CD45RB cells that express a low density of CD45RB (CD45RC in the rat). In this paper we show that CD4+ CD45RB high-density cells are sufficient to cause rejection of a MHC-mismatched pancreas allograft, whereas CD4+ CD45RB low-density cells are not. Unexpectedly, the CD45RB low-density cells prevent the CD45RBhigh expressing cells from causing rejection. These data suggest that the response to foreign tissue can be controlled in the same way as the response to self-tissue.  (+info)

Results of pancreas transplantation after steroid withdrawal under tacrolimus immunosuppression. (11/501)

PURPOSE: The results of steroid withdrawal in pancreas transplant recipients under tacrolimus immunosuppression were analyzed. METHODS: From July 4, 1994 until April 30, 1998, 147 pancreas transplantations were performed in 141 patients, including 126 simultaneous pancreas-kidney transplantations, 13 pancreas after kidney transplantation, and 8 pancreas transplantations alone. Baseline immunosuppression consisted of tacrolimus and steroids without antilymphocyte induction. Twenty-three patients were excluded from analysis because of early graft loss in 17 cases, retransplantation in 5 cases, and simultaneous pancreas-kidney transplantation after heart transplantation in 1 patient. RESULTS: With a mean follow-up of 2.8+/-1.1 years (range 1.0 to 4.8 years), complete steroid withdrawal was achieved in 58 (47%) patients with a mean time to steroid withdrawal of 15.2+/-8 months (range 4 to 40 months after transplantation). Of the entire cohort of 141 patients, overall 1-, 2-, and 4-year patient survival rates were 98%, 95.5%, and 86%, respectively. Overall 1-, 2-, and 4-year graft survival rates were 83%, 80%, and 71% (pancreas) and 95%, 91%, and 84% (kidney), respectively. Of the 124 patients analyzed for steroid withdrawal, 1-, 2-, and 4-year patient survival rates were 98%, 97%, and 92%, respectively. Overall 1-, 2-, and 4-year graft survival rates were 98%, 91.5%, 83% (pancreas) and 97%, 95%, and 91% (kidney). Patient, pancreas, and kidney survival rates at 1 year were 100%, 100%, and 98% (off steroids) versus 97%, 91%, and 96% (on steroids, all NS) and at 4 years were 100%, 94%, and 95% (off steroids) versus 78%, 68%, and 85% (on steroids, P = 0.01, 0.002, and NS, respectively). The cumulative risk of rejection at the time of follow-up was 76% for patients on steroids versus 74% for patients off steroids (P = NS). Seven patients originally tapered off steroids were treated for subsequent rejection episodes, which were all steroid sensitive, and two of these seven patients are currently off steroids. Thirteen patients received antilymphocyte therapy for steroid-resistant rejection, five of whom are now off steroids. Tacrolimus trough levels were 9.3+/-2.4 ng/ml (off steroids) and 9.7+/-4.3 (on steroids, P = NS). Mean fasting glucose levels were 98+/-34 mg/dl (off steroids) and 110+/-41 mg/dl (on steroids, P = NS). Mean glycosylated hemoglobin levels were 5.2+/-0.9% (off steroids) and 6.2+/-2.1% (on steroids, P = 0.02), and mean serum creatinine levels were 1.4+/-0.8 mg/dl (off steroids) and 1.7+/-1.0 mg/dl (on steroids, P = 0.02). CONCLUSION: These data show for the first time that steroid withdrawal can be safely accomplished in pancreas transplant recipients maintained on tacrolimus-based immunosuppression. Steroid withdrawal is associated with excellent patient and graft survival with no increase in the cumulative risk of rejection.  (+info)

Decreased surgical risks of pancreas transplantation in the modern era. (12/501)

OBJECTIVE: To document the decreased incidence of surgical complications after pancreas transplantation in recent times. SUMMARY BACKGROUND DATA: Compared with other abdominal transplants, pancreas transplants have historically had the highest incidence of surgical complications. However, over the past few years, the authors have noted a significant decrease in the incidence of surgical complications. METHODS: The authors studied the incidence of early (<3 months after transplant) surgical complications (e.g., relaparotomy, thrombosis, infections, leaks) after 580 pancreas transplants performed during a 12-year period. Patients were analyzed and compared in two time groups: era 1 (June 1, 1985, to April 30, 1994, n = 367) and era 2 (May 1, 1994, to June 30, 1997, n = 213). RESULTS: Overall, surgical complications were significantly reduced in era 2 compared with era 1. The relaparotomy rate decreased from 32.4% in era 1 to 18.8% in era 2. Significant risk factors for early relaparotomy were donor age older than 40 years and recipient obesity. Recipients with relaparotomy had significantly lower graft survival rates than those without relaparotomy, but patient survival rates were not significantly different. A major factor contributing to the lower relaparotomy rate in era 2 was a significant decrease in the incidence of graft thrombosis; the authors believe this lower incidence is due to the routine use of postoperative low-dose intravenous heparin and acetylsalicylic acid. The incidence of bleeding requiring relaparotomy did not differ between the two eras. Older donor age was the most significant risk factor for graft thrombosis. The incidence of intraabdominal infections significantly decreased between the two eras; this decrease may be due to improved prophylaxis regimens in the first postoperative week. CONCLUSIONS: Although a retrospective study has its limits, the results of this study, the largest single-center experience to date, show a significant decrease in the surgical risk associated with pancreas transplants. Reasons for this decrease are identification of donor and recipient risk factors, better prophylaxis regimens, refinements in surgical technique, and improved immunosuppressive regimens. These improved results suggest that more widespread application of pancreas transplantation is warranted.  (+info)

Comparison of two commercial methods for measurement of cytomegalovirus load in blood samples after renal transplantation. (13/501)

A cohort of 77 renal transplant recipients was prospectively studied for comparison of two commercially available cytomegalovirus (CMV) load assays, i.e., the COBAS AMPLICOR CMV Monitor test (Amplicor), using plasma samples, and the Murex Hybrid Capture System (HCS), using whole blood. The manufacturer of the HCS assay changed the version of the test from 1.0 (HCS-1) to 2.0 (HCS-2) after the first 37 patients had been tested. Despite the differences in principle and type of specimen used, the Amplicor and HCS assays gave comparable results. The regression line correlating the HCS-1 assay to the Amplicor assay was similar to that correlating the HCS-2 assay to the Amplicor assay. The HCS results could be converted to Amplicor-equivalent units by using linear-regression equations [log(10) HCS-1 result = 0.49 (log(10) Amplicor result) + 2.58, and log(10) HCS-2 result = 0.61 (log(10) Amplicor result) + 2.18]. The HCS-2 assay appeared to have the lowest detection limit, followed by the Amplicor assay and then the HCS-1 assay. When a sliding scale of cutoff values in Amplicor-equivalent units (>1,000, >2,500, >6,000, >16,000, >40,000, and >100,000 copies/ml) was applied to diagnose CMV disease, similar patterns of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were observed with the Amplicor and HCS assays. A cutoff value of >40,000 copies/ml has a low sensitivity (Amplicor, 29.4%; HCS, 41.2%) but is specific (Amplicor, 96.7%; HCS, 93.3%) and can be used for the differential diagnosis of CMV disease (PPV, 71.4% [Amplicor] or 63. 6% [HCS]; NPV, 82.9% [Amplicor] or 84.8% [HCS]). A lower cutoff value of >1,000 copies/ml improves the sensitivity (Amplicor, 76.5%; HCS, 82.4%) and has a high NPV (Amplicor, 91.8%; HCS, 94.2%) but, due to the low PPV (Amplicor, 46.2%; HCS, 56%), is useful only for exclusion of CMV disease.  (+info)

Simultaneous pancreas-kidney transplantation and living related donor renal transplantation in patients with diabetes: is there a difference in survival? (14/501)

OBJECTIVE: To compare the outcome of simultaneous pancreas-kidney transplantation (SPK) and living related donor renal transplantation (LRD) in patients with diabetes. SUMMARY BACKGROUND DATA: It remains unanswered whether diabetic patients with end-stage renal failure are better served by LRD or SPK. METHODS: Using a longitudinal database, data from all diabetic patients receiving LRD or cadaveric renal transplants or SPKs from January 1986 through January 1996 were analyzed. Patient and graft survival, early graft function, and the cause of patient and graft loss were compared for 43 HLA-identical LRDs, 87 haplotype-identical LRDs, 379 SPKs, and 296 cadaveric renal transplants. RESULTS: The demographic composition of the SPK and LRD groups were similar, but because of less strict selection criteria in the cadaveric transplant group, patients were 10 years older, more patients received dialysis, and patients had been receiving dialysis longer before transplantation. Patient survival was similar for the SPK and LRD groups but was significantly lower for the cadaveric renal transplant group. Similarly, there was no difference in graft survival between SPK and LRD recipients, but it was significantly lower for recipients in the cadaveric renal transplant group. Delayed graft function was significantly more common in the cadaveric renal transplant group. Discharge creatinine, the strongest predictor of patient and graft survival, was highest in the SPK group and lowest in the HLA-identical LRD group. The rate of rejection within the first year was greatest in SPK patients (77%), intermediate in the haplotype-identical LRD and cadaveric transplant groups (57% and 48%, respectively), and lowest (16%) in the HLA-identical LRD group. Cardiovascular disease was the primary cause of death for all groups. Acute rejection, chronic rejection, and death with a functioning graft were the predominant causes of graft loss. CONCLUSIONS: This study demonstrates that there was no difference in patient or graft survival in diabetic patients receiving LRD or SPK transplants. However, graft and patient survival rates in diabetic recipients of cadaveric renal transplants were significantly lower than in the other groups.  (+info)

Three cases of pancreas allograft dysfunction. (15/501)

We present dincopathologic features of three cases of biopsy-proven pancreas allograft dysfunction in Korea. All patients had advanced insulin-dependent diabetes mellitus (IDDM). Case 1 was a 30-year-old woman who underwent a simultaneous pancreas-kidney transplantation. Urinary infection developed 6 days after the operation, which remitted and reappeared, when urine amylase level was normal. Since the 55th day after the operation, intermittent hematuria has persisted. Cytomegalovirus inclusions were detected on the urinary bladder and grafted duodenal mucosa. The graft was removed due to perforation of the grafted duodenum and panperitonitis. Case 2 was a 27-year-old man undergoing pancreas transplantation alone (PTA). Ten days after the transplatation, the level of 24 urine amylase decreased and the graft was not delineated by 99mTc DTPA scintigraphy. Allograft needle biopsy revealed multiple acinar cell necrosis and mild lymphocytic infiltration which were compatible with mild acute rejection. Case 3 was a 25-year-old man undergoing cadevaric PTA. Three months after the transplantation, graft was removed due to gastric perforation associated with cytomegalovirus and angiodestructive fungal infection. Various causes of pancreas allograft dysfunction can be diagnosed by needle biopsy, thus appropriate biopsy specimen should be taken using improved biopsy technique.  (+info)

Simultaneous pancreas-kidney transplantation reduces excess mortality in type 1 diabetic patients with end-stage renal disease. (16/501)

BACKGROUND: Diabetic renal disease continues to be the most significant cause of end-stage renal disease (ESRD) in the United States. Renal transplantation improves diabetic ESRD patient survival; however, the diabetic state remains associated with poor patient survival. Simultaneous pancreas-kidney (SPK) transplantation can restore normoglycemia and thus may improve outcomes. METHODS: We assessed the impact of SPK on age-range-matched type 1 diabetic patients who underwent renal transplantation at a single center. The observed/expected life span and annual mortality rates (AMRs) were used as measures of survival. A Cox proportional hazards analysis was used to analyze the impact of potential variables on mortality in SPK recipients. RESULTS: SPK transplantation (N = 335) increased the observed/expected life span compared with diabetic cadaveric (DM-Cad, N = 147) and live-donor (DM-Live, N = 160) transplant recipients (P = 0.004) and significantly reduced the AMRs (SPK, 1. 5%; DM-Cad, 6.27%; DM-Live, 3.65%, P = 0.008, SPK vs. other DM). Moreover, the SPK observed/expected life span and AMR were not significantly different from that of age-range-matched nondiabetic transplant recipients (N = 492). The only variable that was significantly associated with patient survival was discharge serum creatinine (relative risk 1.16, P < or = 0.0154). CONCLUSION: These data demonstrate that SPK improves the ability for type 1 diabetic patients to live more of their expected life span. This suggests that glycemic control, even as a late intervention in a diabetic patient's lifetime, may beneficially affect survival.  (+info)