Results of positive cross-match transplantation in African American renal transplant recipients.

Positive cross-match (PXM) renal transplantation has been utilized to address the issue of the increasing demand for transplantation with the shortage of suitable organs. Our primary objective was to analyze the outcomes of African American (AA) PXM renal transplant recipients utilizing AA negative cross-match (NXM) renal transplant recipients as a comparator group. This was a retrospective study consisting of all PXM patients who underwent a desensitization protocol and all AA NXM transplant recipients at the University of Illinois at Chicago from July 2001 to March 2007. We found that AA PXM recipients had significantly lower estimated glomerular filtration rate (eGFR) at 1 year than AA NXM (46.2 vs. 60.6, p = 0.007). AA PXM who experienced acute rejection within the first year were more likely to have an eGFR less than 30 mL/min/1.73 m(2) at 1 year compared to their NXM counterparts (45.5% vs. 12.5%, p = 0.034). Positive cross-match renal transplantation in AA seems to be associated with a high degree of AR and severe renal compromise at 1 year. Larger studies are needed to determine if protocols that are associated with good short-term outcomes in non-AA need to be modified for the AA population.

Progressive functional adaptation of segmental bowel graft from living related donor.

We report a patient with short gut syndrome successfully treated with living related bowel transplantation. A 27-year-old Caucasian man was referred after traumatic loss of almost the entire bowel from the third portion of duodenum to the sigmoid colon. His HLA-identical sister volunteered as a donor. A 200-cm segment of ileum was successfully transplanted under tacrolimus-based immunosuppression. The posttransplant course was uneventful, without rejection or infectious complication. Total parenteral nutrition was discontinued 1 week posttransplant. At 6 months the patient had returned to his preinjury weight. Water and D-xylose absorption as well as fecal fat studies were markedly abnormal 1 month posttransplant but normalized by 6 months. The donor recovery was uneventful. A well-matched segmental ileal graft from living donor can provide complete rehabilitation for patients with short gut syndrome. We documented a progressive functional adaptation of the ileal graft, resulting in normal absorption by 5 months posttransplantation.

Multiple intrasplenic hepatocyte transplantations in the dalmatian dog.

BACKGROUND: Hepatocyte transplantation is an attractive potential treatment for liver-based inborn errors of metabolism and for fulminant hepatic failure. Dalmatian dogs have a metabolic error that results in hyperuricosuria. This report focuses on the effect of multiple, sequential intrasplenic transplants of fresh and cryopreserved hepatocytes in dalmatians. METHODS: Dalmatians underwent intrasplenic hepatocyte transplantation with hepatocytes taken from healthy mongrels. Dalmatian urinary uric acid excretion was measured preoperatively, and this served as the control value. Three hepatocyte transplantations were performed at 30-day intervals--the first with freshly isolated cells, and both the second and the third with cryopreserved hepatocytes from the same donor. Urinary uric acid excretion was measured postoperatively twice per week. RESULTS: The urinary uric acid excretion decreased an average of 54% after the first hepatocyte transplantation. The effect was transient and lasted an average of 22 days (range, 19-50 days). Subsequent intrasplenic hepatocyte transplantation with cryopreserved hepatocytes resulted in similar decreases in urinary uric acid excretion. Each transplant resulted in a significant decrease in urinary uric acid excretion when compared with baseline values (P = < .001). CONCLUSIONS: Sequential intrasplenic hepatocyte transplantation is feasible in this model. This method provided a significant, but transient, correction in urinary uric acid excretion that was similar with either fresh or cryopreserved hepatocytes. A substantial biologic effect provided by cryopreserved hepatocytes has important implications in clinical hepatocyte transplantation.

Comparison of rejection rate and functional outcome of small bowel transplantation alone or in conjunction with the ileocecal valve versus combined small and large bowel transplantation.

Preservation of the ileocecal valve improves absorptive function and decreases the amount of small bowel needed for survival in patients with short gut syndrome. We compared the results of small and large bowel transplant (SLBTx), small bowel transplant only (SBTx), and SBTx with the ileocecal valve (ICVTx) in a porcine model. Total enterectomy was performed on 18 Yorkshire-Landrace pigs followed by orthotopic SBLTx (n = 6), SBTx (n = 6), and ICVTx (n = 6). A jejunostomy and an ileostomy were constructed for biopsies. Overall mean survival was 17 d with no statistically significant difference between groups. Rejection was seen in 6/6 SLBTx, 4/6 SBTx, and 4/6 ICVTx recipients. Acute rejection was seen in 84.3% of SLBTx, 52.3% of SBTx, and 42.5% of the ICVTx mucosal biopsy samples. Two cases of intra-abdominal infection were in the ICVTx group only. Weight loss was 147 g/d in the SLBTx group, 643 g/d in the SBTx group, and 393 g/d in the ICVTx group. While the functional outcome after SLBTx and ICVTx was noticeably better than the SBTx group, the increased rejection and intra-abdominal infection rates make transplanting the large bowel or the ileocecal valve a less attractive clinical option.

Comparison of jejunal and ileal surveillance biopsies in a porcine model of intestinal transplantation.

BACKGROUND: The optimal biopsy site of bowel allografts for rejection surveillance remains controversial. We compared the results of jejunal (JBx) and ileal (IBx) biopsies after bowel transplantation in a porcine model. METHODS: Eighteen Yorkshire-Landrace pigs served as donors. Eighteen recipient pigs underwent total enterectomy followed by orthotopic small bowel transplantation with or without the colon. A jejunostomy and a Bishop-Koop ileostomy were constructed for biopsies. Immunosuppression consisted of FK506 (target level 10-15 ng/ml by enzyme immunoparticle assay) and prednisone administered via the jejunostomy. Simultaneous JBx and IBx were performed twice weekly. Acute rejection was graded as mild, moderate, or severe based on previously published criteria. RESULTS: Mean overall survival after the transplant was 17.4 days. A total of 162 specimens were collected and evaluated for rejection (JBx, 81; IBx, 81). Acute rejection was detected in 41 JBx cases (50.7%) and 40 IBx cases (49.4%). The presence or absence of rejection was concordant between JBx and IBx in 70 of 81 case pairs (86.4%). Of the 11 discordant case pairs, 6 were JBx positive/IBx negative, whereas 5 were JBx negative/IBx positive. A total of 35 case pairs were synchronously positive, 24 (68.8%) of which demonstrated the same degree of rejection. CONCLUSIONS: The correlation between JBx and IBx of bowel allografts in diagnosing the presence of acute rejection is quite good. However, performing IBx alone would have missed about 7.5% of the rejection episodes. Because the early treatment of rejection in bowel transplantation is of paramount importance, in selected cases, biopsies from both the ileum and jejunum should be considered if technically feasible.

A prospective randomized trial comparing the efficacy of tacrolimus versus cyclosporine in black recipients of primary cadaveric renal transplants.

BACKGROUND: We performed a prospective randomized trial to compare the efficacy and safety of tacrolimus (FK506) versus cyclosporine (CSA) in black primary cadaveric renal transplant (CRT) recipients. METHODS: Between December 1994 and February 1997, 35 black primary CRT recipients were enrolled in this trial. All patients received 7 days of induction therapy with OKT3. Fourteen patients received FK506 and prednisone only. Twenty-one patients received CSA, azathioprine, and prednisone. The two groups were comparable in terms of age, gender, plasma renin activity, human leukocyte antigen mismatches, and cause of renal failure. RESULTS: Patient and graft survival were 12 of 14 (86%) for the FK506 group and 20 of 21 (95%) for the CSA group (P = 0.71). Three patients died owing to cardiac events with functioning grafts. Acute rejection was 2 of 14 (14%) for the FK506 and 8 of 21 (38%) for the CSA group (P = 0.25). Two other patients on CSA were converted to FK506 as rescue for OKT3-resistant rejection. Mean serum cholesterol at 1 year was 198 +/- 45 mg/dL for the FK506 group and 244 +/- 49 mg/dL for the CSA group (P = 0.03). Mean serum creatinine at 1 year was 1.39 +/- 0.38 mg/dL for the FK506 group and 1.94 +/- 0.64 mg/dL for the CSA group (P = 0.02). CONCLUSION: Patient and graft survival were similar in both groups at 1 year posttransplant. Although statistically not significant, the incidence of acute rejection was lower in the FK506 group. Furthermore, FK506-treated patients had significantly lower serum creatinine and cholesterol levels at 1 year posttransplant.

Successful living related simultaneous pancreas-kidney transplant between identical twins.

Simultaneous pancreas-kidney transplant from living donors has been recently proposed as an effective therapeutic option in selected uremic patients with type I diabetes. We report the first simultaneous pancreas-kidney transplant performed between identical twins. Posttransplant, the recipient has been maintained on low dose cyclosporine to avoid recurrent auto-immune insulitis. At the 1-year follow-up, both donor and recipient are well with normal renal function and excellent glucose control. Simultaneous pancreas-kidney transplant between identical twins can be performed successfully using cyclosporine to prevent recurrent auto-immune insulitis.

Long-term outcome of a prospective trial of steroid withdrawal after kidney transplantation.

BACKGROUND: Steroid withdrawal (SW) after kidney transplantation is desirable to avoid associated serious side effects. We studied the long-term outcome of a group of kidney transplant recipients who underwent SW. METHODS: Between 1991 and 1993, kidney transplant recipients (N = 12) who had posttransplantation diabetes were entered in a prospective trial of SW. These patients were compared with a demographically similar comparison cohort (N = 66). End points of the study were patient and graft survival, incidence of late acute and chronic rejection, and changes in diabetes management. RESULTS: Previously published data from the SW group at 15 months of follow-up indicated improvement in diabetes control without any adverse effect on patient or graft actuarial survival. At long-term follow-up (mean, 56 months) the improvement in diabetes management was not detectable. The incidence of late acute rejection in SW and cohort groups was 42% and 8%, respectively (P = .006). Likewise, the incidence of chronic rejection in the SW versus cohort group was 42% and 12%, respectively (P = .014). CONCLUSIONS: Although SW appeared to be successful initially, our long-term data indicate that SW significantly increases the risk of late acute rejection and chronic rejection episodes without benefits in posttransplantation diabetes management. Steroid withdrawal in patients with posttransplantation diabetes should be approached with caution.

A prospective study of the predictive value of polymerase chain reaction assay for cytomegalovirus in asymptomatic kidney transplant recipients.

Cytomegalovirus (CMV) infection carries the potential for high morbidity in transplant recipients. The institution of pre-emptive therapy prior to the onset of clinical disease on the basis of CMV-polymerase chain reaction (PCR) is very attractive. We prospectively studied 52 asymptomatic kidney transplant recipients to test the hypothesis that serial CMV-PCR assays during the first 3 months post-transplant would identify patients at risk for CMV disease. Twenty-three patients (44.2%) had positive CMV-PCR tests at least once; 2 (8.6%) developed CMV. None of the 29 patients continuously negative for CMV-PCR developed CMV disease. CMV-PCR status did not influence patient and graft survival or the incidence of acute rejection. We conclude that while a substantial number of kidney transplant recipients become positive for CMV-PCR in the early post-transplant period, only a minority will develop CMV disease. Negative CMV-PCR assay is an accurate negative predictor for CMV disease but the value of CMV-PCR as a guide for pre-emptive anti-CMV therapy in kidney transplant recipients appears limited.

A new rat model to study the correlation of cardiac and skeletal muscle allograft rejection.

As a first step to study the correlation of cardiac and skeletal muscle allograft rejection, we describe a new experimental rat model of simultaneous heterotopic heart and cutaneous maximus muscle flap allotransplant. Brown Norway rats were used as donors and Lewis rats as recipients. No immunosuppression was given. The grafts were revascularized with sequential end-to-side anastomosis of each vascular pedicle to the infrarenal aorta and vena cava. Syngeneic heart and cutaneous maximus muscle grafts remained functional and showed no sign of rejection at 7 days after the transplant. In contrast, both allografts developed severe rejection and functional compromise at 7 days after the transplant. Our experimental model is technically feasible and reproducible and may provide important information about the pattern of rejection of cardiac and skeletal muscle allografts.