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Background: In this study, we present our experience with ureteral complications requiring revision surgery after renal transplantation and compare our results to a matched control population., Methods: We performed a retrospective analysis of our database between 1997 and 2012. We divided the cases into early (<60 d) and late repairs. Kaplan-Meier and Cox proportional hazards models were used to compare graft survival between the intervention cohort and controls generated from the Scientific Registry of Transplant Recipients data set., Results: Of 2671 kidney transplantations, 51 patients were identified as to having undergone 53 ureteral revision procedures; 43.4% of cases were performed within 60 d of the transplant and were all associated with urinary leaks, and 49% demonstrated ureteral stenosis. Reflux allograft pyelonephritis and ureterolithiasis were each the indication for intervention in 3.8%; 15.1% of the lesions were located at the anastomotic site, 37.7% in the distal segment, 7.5% in the middle segment, 5.7% proximal ureter, and 15.1% had a long segmental stenosis. In 18.9%, the location was not specified. Techniques used included ureterocystostomy (30.2%), ureteroureterostomy (34%), ureteropyelostomy (30.1%), pyeloileostomy (1.9%), and ureteroileostomy (3.8%). No difference in overall graft survival (HR 1.24 95% CI 0.33-4.64, p = 0.7) was detected when compared to the matched control group., Conclusion: Using a variety of techniques designed to re-establish effective urinary flow, we have been able to salvage a high percentage of these allografts. When performed by an experienced team, a ureteric complication does not significantly impact graft survival or function as compared to a matched control group., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Several studies indicate that the poorer outcomes for African--Americans after transplantation may be due to decreased effectiveness of immunosuppressive agents. Using an in vitro test of immunocompetence (IMC), we measured the effects of immunosuppression on African-American, compared with Caucasian, kidney or liver transplantation recipients. The IMC result was the highest of three mixed lymphocyte culture responses using validated stimulator cell pools. A total of 293 tests were done in Caucasians and 144 in African--Americans. Overall, the IMC for African--Americans was 38, compared with 19 for Caucasians (p<0.01). This decreased effect of immunosuppression (higher IMC) was the same for liver as for kidney transplant recipients, occurred at the 2--3-yr interval, and was largely in patients of tacrolimus (FK506), with a strong but not significant trend in cyclosporine (CYA) recipients. The two groups were on the same nominal immunosuppression and FK506 and CYA levels were not different. We conclude that African-Americans retain more immune responsiveness on equivalent dose immunosuppression, notable particularly in years 2--3 after transplantation when earlier graft loss occurs in this group.

Introduction: The purposes of this study were: 1) to analyze the early results of cadaveric renal transplantation from either hepatitis C virus seropositive (HCV+ ) or hepatitis C virus seronegative (HCV-) donors into HCV + recipients; and 2) to determine whether HCV+ patients with end-stage renal disease (ESRD) might benefit from receiving renal allografts from HCV + donors., Methods: From January 1997 to June 1999, 28 patients with ESRD and HCV infection underwent 29 cadaveric renal transplants. The data were reviewed retrospectively. Nineteen of the renal transplants were performed with allografts obtained from 15 HCV + donors and 10 with allografts obtained from 10 HCV- donors. The median follow-up was 16.2 months, with an average of 15.4+/-2 months., Results: Recipients of HCV + renal allografts had shorter waiting times for transplantation. On average, patients who received a kidney from HCV + donors were transplanted 9+/-3 months after being placed on the transplant list, compared to 29+/-3 months for patients who received a kidney from a HCV- donor. Shorter waiting times were noted in every blood type group. There were no significant differences in rejection episodes, infectious complications, renal function, liver function, graft survival, or patient survival., Conclusions: The use of renal allografts from HCV + donors for HCV + recipients shortens the waiting time for these patients, with no short-term differences in renal and liver function, graft loss, or patient survival.

The P450 inhibitor ketoconazole may be used to decrease the dose, and therefore cost, of cyclosporine (CYA) by greatly decreasing the dose necessary to obtain therapeutic levels. However, the degree of immunosuppression produced using this drug regimen is not certain. We studied the immunocompetence of patients that had been started on ketoconazole to reduce the dose of CYA compared with patients treated conventionally. 95 assays were done in 64 patients including 6 assays in patients receiving low dose CYA plus ketoconazole. Immunocompetence was tested by measuring the mixed lymphocyte response using stimulators either non-depleted (ND) or depleted (D) of antigen presenting cells, based on the finding that CYA inhibits the response against D at a lower dose than against ND. Responses to ND/D ranged from +/+ through +/- to -/-. Normal individuals were always +/+. In conventionally treated patients with CYA the incidence of immunocompetence < or = +/- was 48%, whereas all patients on CYA + ketoconazole had an immunocompetence score < or = +/- (p = 0.03, chi 2). This degree of immunosuppression contrasted strikingly with the chemical levels, which for those on ketoconazole were in the low acceptable area (182.3 +/- 77.1 ng/ml range from 67 to 230 ng/ml). Therefore, patients using low-dose CYA plus ketoconazole to inhibit metabolism were more immunosuppressed than those receiving conventional CYA treatment, in spite of comparable CYA blood levels. If confirmed, this unexpectedly depressed immunocompetence in these patients would warrant caution in general regarding interpretation of trough blood levels in patients receiving CYA that are also being treated with agents that alter P450 activity.

We hereby report our experience with an index case of a pediatric liver transplant patient in whom FK506 administration was associated with the development of proximal renal tubular acidosis (RTA), as well the prevalence of acidosis and renal dysfunction in all pediatric liver transplant patients in our institution followed long term during a 6-year period. Data were grouped according to immunosuppressant regime: cyclosporine (CsA) only, FK506 only, or CsA with conversion to FK506. A 23-month-old female treated with FK506 after orthotopic liver transplantation (OLT) performed 15 months earlier presented with a 1-wk history of fever, watery diarrhea and metabolic acidosis. Although the acidosis did not improve following correction of her hydration status, administration of oral bicarbonate was effective. Discontinuation of this therapy resulted in acidosis. Since other indirect measurements of renal tubular function were normal, the patient was judged to have an isolated proximal RTA. In our group of pediatric liver transplant patients converted from CsA to FK506, FK506 administration was associated with a decline in serum bicarbonate (19 +/- 1 vs. 16 +/- 1 mEq/l, p < 0.02); neither blood urea nitrogen nor serum creatinine differed between the two groups. The number of rejection episodes/patient/month was comparable, allowing clinically relevant comparison of relative drug nephrotoxicities. We conclude that proximal RTA may be a relatively common treatable complication of FK506 administration in children.