Dilly M. Little

Improved patient survival in recipients of simultaneous pancreas-kidney transplant compared with kidney transplant alone in patients with type 1 diabetes mellitus and end-stage renal disease

There are emerging data that simultaneous pancreas–kidney transplant (SPK) prolongs life compared with kidney transplant alone (KTA) in type 1 diabetics with end‐stage renal disease. This study was a retrospective comparison of SPK with KTA in patients with type 1 diabetes.

Urological Complications of Pancreatic Transplantation

PURPOSE Pancreas transplantation is increasingly being used in the treatment of type I insulin-dependent diabetes mellitus. Because bladder drainage of the exocrine pancreatic secretion is the procedure of choice, urological complications are frequent. As the number of these procedures increases the urologist will have an extended role in the management of the postoperative complications, the majority of which are urological. MATERIALS AND METHODS The literature from 1985 on the complications related to pancreas transplants was reviewed. RESULTS Approximately 50 to 60% of bladder drained pancreas transplant recipients will have a urological complication postoperatively. CONCLUSIONS The increasing application of bladder drained pancreas transplantation in the treatment of type I insulin-dependent diabetes mellitus necessitates that the clinical urologist is familiar with the management of complications related to this procedure.

MDRD-Estimated GFR at One Year Post-Renal Transplant Is a Predictor of Long-Term Graft Function

Renal transplantation is the optimal mode of renal replacement. Improvements in graft survival and acute rejection rates have made these outcomes less useful for prognostication and as end-points in clinical trials; accurate surrogate markers of long-term graft outcome are therefore increasingly important. This study examines the relationship between both serum creatinine (SCr1yr) and MDRD estimated glomerular filtration rate measured at one year (eGFRMDRD1yr) as predictors of graft survival. Data on 1,110 patients who received a renal transplant between 1989 and 2005 were extracted from the Irish Renal Transplant Registry. The study group was divided into quartiles of patient numbers according to SCr1yr and eGFRMDRD1yr. Kaplan-Meier estimates of the primary end-point graft survival were constructed for each quartile. Additionally, a Cox Regression restricted cubic spline model was performed for both eGFRMDRD1yr and SCr1yr. Both overall graft outcome and outcome censored for death with a functioning graft (CDWFG) were used as endpoints. Cox regression analysis was performed along with tests for the proportionality assumption to compare the predictive value of eGFRMDRD1yrand SCr1yr. Both eGFRMDRD1yr and SCr1yr were independently associated with long-term renal transplant survival. eGFRMDRD1yr and SCr1yr had similarly strong associations with long-term outcome when the quartile variables were compared using the Bayesian Information Criterion method. The Cox regression restricted cubic spline modeling demonstrated that an eGFRMDRD1yr value < 27 mLs/min/1.73m2 and a SCr1yr value > 229 μmol/L were associated with poor graft survival.

A single-center study of the technical aspects and outcome of third and subsequent renal transplants.

Background. Third, fourth, and fifth renal transplants are historically associated with poor outcomes. The reasons for these inferior results are unclear. In the current work, we analyzed the outcome of third and subsequent transplants and determined whether technical failure accounted for significant allograft loss. Methods. The outcome and operative details of 49 transplants performed in 38 patients from a single center were reviewed. Thirty-eight patients received a third transplant, nine patients received a fourth transplant, and two patients received a fifth transplant. Results. Actuarial patient survival was 100% and 97% at 5 and 10 years, respectively. One- and 5-year actuarial graft survival for third transplants was 90% and 62%, respectively, and for fourth transplants, 67% and 55%, respectively. Technical failure accounted for the loss of 2 third allografts and for no fourth or fifth allografts. Of the remaining third grafts, 12 failed as the result of chronic allograft nephropathy, and one failed as the result of recurrent membranoproliferative glomerulonephritis (type I). Of the fourth allografts, one failed as the result of acute rejection, two failed as the result of chronic allograft nephropathy, and one failed as the result of primary nonfunction. The mean graft survival of third and fourth transplants after a biopsy-proven acute rejection episode requiring steroid boost was significantly reduced. Of the fifth transplants, one graft failed as the result of hyperacute rejection, and one patient died with a functioning graft. Favorable human leukocyte antigen matching and a panel-reactive antibody less than 80% provided no statistical benefit to graft survival. Conclusions. The major cause of graft loss of third and fourth renal transplants is immune mediated. Although technically demanding, surgical failure is an unusual cause of graft loss.

LONG-TERM FOLLOWUP OF CADAVERIC RENAL TRANSPLANTATION IN PATIENTS WITH SPINA BIFIDA

PURPOSE Access related problems in hemodialysis and peritoneal dialysis are increased in cases of spina bifida due to vascular and body habitus limitations. Reports of renal transplantation in this patient group are exceedingly rare. We report long-term followup data on cadaveric renal transplantation for end stage renal failure in cases of spina bifida. MATERIALS AND METHODS Between February 1986 and April 2000, 17 cadaveric renal transplants were performed in 11 females and 5 males with spina bifida. Mean age at transplantation was 20.2 years (range 10 to 35). Of the patients 11 were wheelchair bound and 5 were independently mobile. Before transplantation surgical management of the urological tract included clean intermittent self-catheterization in 3 cases, enterocystoplasty and clean intermittent self-catheterization in 8, and ileal conduit urinary diversion in 5. A total of 14 patients were on renal replacement therapy before receiving the graft. Cyclosporine based triple therapy was administered to maintain immunosuppression in all cases and antithymocytic globulin was given for induction in 7. RESULTS Six grafts have failed, including 1 in a patient who underwent successful re-transplantation. Median graft survival was 7.23 years. Two patients died after graft nephrectomy. At a mean followup of 52.8 months (range 1 month to 14 years) 11 of 17 grafts are functioning with a mean serum creatinine of 112.7 +/- 29.4 mmol./l. CONCLUSIONS These data demonstrate the feasibility of cadaveric renal transplantation in patients with spina bifida and end stage renal failure. We currently recommend that these patients should not be deprived of the benefits of renal transplantation.

Renal allograft loss in the first post‐operative month: causes and consequences

Phelan PJ, O’Kelly P, Tarazi M, Tarazi N, Salehmohamed MR, Little DM, Magee C, Conlon PJ. Renal allograft loss in the first post‐operative month: causes and consequences.

Improved graft survival in highly sensitized patients undergoing renal transplantation after the introduction of a clinically validated flow cytometry crossmatch.

Background. Flow cytometric techniques are increasingly used in pretransplant crossmatching, although there remains debate regarding the clinical significance and predictive value of donor-specific antibodies detected by flow cytometry. At least some of the discrepancies between published studies may arise from differences in cutoffs used and lack of standardization of the test. Methods. We selected cut-off values for pretransplant flow cytometric crossmatching (FCXM) based on the correlation of retrospective results with the occurrence of antibody-mediated rejection. The impact on long-term renal graft survival of prospective FCXM was determined by comparing graft survival between patients crossmatched with complement-dependent cytotoxicity (CDC) only with those prospectively crossmatched with both CDC and FCXM. Results. Chosen cut-off values gave a positive predictive value of FCXM for antibody-mediated rejection of 83%, and a negative predictive value of 90%. After the introduction of prospective B- and T-cell crossmatching by flow cytometry in addition to CDC in our center, there was a significant improvement in renal graft survival in highly sensitized patients (P=0.017). Four-year graft survival in highly sensitized patients after the introduction of FCXM was 89%, which did not differ significantly from that seen in nonsensitized patients (93%; P=0.638). Conclusions. Our data demonstrate that prospective FCXM improves renal transplant outcome in highly sensitized patients, provided that cut-off values are carefully validated and results interpreted in the context of sensitization history and antibody screening results.

Immediate re‐transplantation following early kidney transplant thrombosis

Allograft thrombosis is a devastating early complication of renal transplantation that ultimately leads to allograft loss. We report here on our experience of nine cases of immediate re‐transplantation following early kidney transplant thrombosis at a single centre between January 1990 and June 2009. The mean age was 42.9 years at time of transplant. For seven patients, the allograft thrombosis was their first kidney transplant and seven of the nine cases had a deceased donor transplant. The initial transplants functioned for a mean of 1.67 days and the patients received a second allograft at a mean of 3.1 days after graft failure. All of the re‐transplants worked immediately. Four allografts failed after a mean of 52.5 months (2–155 months). Two of these died with a functioning allograft, one failed owing to chronic allograft nephropathy and one owing to persistent acute cellular rejection. The remaining five patients still have a functioning allograft after a mean of 101.8 months (7–187 months). One year allograft and patient survival after re‐transplantation were 87.5% and 100% respectively (after 5 years, both were 57%). Immediate re‐transplantation following early kidney transplant thrombosis can be a success. It may be considered in selected cases after allograft thrombosis.

Successful renal transplantation in children with spina bifida: Long term single center experience

Abstract:  We report long‐term follow up data on cadaveric renal transplantation for end stage renal failure (ESRF) in spina bifida children. Between February 1989 and July 2001, 12 cadaveric renal transplants were performed in 10 children, eight females and two males. Mean age at transplantation was 13.4 yr (range 9–16). Of the patients, eight were wheelchair bound and two were independently mobile. Before transplantation surgical management of the urological tract included, enterocystoplasty and clean intermittent‐self catheterization in five patients and ileal conduit urinary diversion in one. A total of eight patients were on renal replacement therapy before receiving the graft while two underwent pre‐emptive transplantation. The 1‐ and 5‐yr graft survival rates were 81 and 81%, respectively. Four grafts failed – two patients have successfully undergone subsequent transplantation. Causes of graft failure were chronic rejection in two, acute rejection and vascular thrombosis in one and vascular thrombosis in one patient, respectively. Two patients died after graft nephrectomy. At a median follow‐up of 4.08 yr (range 1 day to 10.65 yr), eight of the 12 grafts are functioning with median serum creatinine of 123 mmol/L (range 65–169). These data demonstrate the feasibility of cadaveric renal transplantation in patients with spina bifida and ESRF. We currently recommend that patients with spina bifida should not be deprived of the benefits of renal transplantation.

Rabbit antithymocyte globulin related decrease in platelet count reduced risk of pediatric renal transplant graft thrombosis

Abstract:  Graft thrombosis is a serious complication in pediatric renal transplantation. We assess a potential protective effect for the decrease in platelet count associated with RATG therapy against pediatric renal transplant graft vascular thrombosis. Between January 1986 and December 1998, 120 kidney transplants were performed in 95 pediatric recipients. Patients were divided into two groups. Group 1 (n = 61), non‐RATG group received cyclosporine, azathioprine and steroids, while group 2 (n = 59), RATG group, received in addition, RATG at day 1 and continued for 4–10 days postoperatively. Platelet count prior to transplant, median change in absolute platelet count at 1 and 3 days post‐transplant was recorded. Graft thrombosis incidence was examined. Six grafts (5%) developed thrombosis. All were in group 1 (p = 0.028). Median pretransplant platelet count (×109/L) in group 1 was 283 vs. 280 in group 2 (p = 0.921). Median decrease in absolute platelet count (×109/L) from pretransplant levels at one and three days post‐transplant for group 1 and 2 was 18 vs. 83 (p ≤ 0.001) and 39 vs. 105 (p ≤ 0.001), respectively. Graft thrombosis risk factors were similar in both groups. RATG use was statistically significant (p = 0.044) for reduced risk of graft thrombosis in multivariate analysis. Patients receiving RATG showed significant decrease in both platelet count and graft thrombosis incidence. A role for RATG related effect on platelet count is assumed.