William C. Goggins

A prospective, randomized, clinical trial of intraoperative versus postoperative thymoglobulin in adult cadaveric renal transplant recipients

Background. Delayed graft function (DGF) is frequently observed in recipients of cadaveric renal transplants. Previous retrospective or nonrandomized studies have suggested that intraoperative administration of polyclonal antithymocyte preparations may reduce the incidence of DGF, possibly by decreasing ischemia-reperfusion injury. Methods. We performed a prospective randomized study of Thymoglobulin induction therapy in adult cadaveric renal transplant recipients. Between January 2001 and January 2002, 58 adult cadaveric renal transplant recipients were randomized to receive intraoperative or postoperative Thymoglobulin induction therapy. Three to six doses of Thymoglobulin (1 mg/kg/dose) were administered during the first week posttransplant. Baseline immunosuppression consisted of tacrolimus (54 of 58) or cyclosporine A (4 of 58), steroids, and mycophenolate mofetil. DGF was defined by the requirement for hemodialysis within the first week posttransplant. Results. There were no significant differences between the two groups in recipient demographics, donor age, cold ischemia time, or total number of doses of Thymoglobulin administered. Intraoperative Thymoglobulin administration was associated with significantly less DGF and a lower mean serum creatinine on postoperative days 10 and 14 (P <0.05). Posttransplant length of stay was also significantly shorter for the intraoperative Thymoglobulin patient group. The acute rejection rate was also lower in the intraoperative treatment group but this did not achieve statistical significance. There was no difference in the incidence of cytomegalovirus disease between the two groups. Conclusions. The results of this study indicate that intraoperative Thymoglobulin administration, in adult cadaveric renal transplant recipients, is associated with a significant decrease in DGF, better early allograft function in the first month posttransplant, and a decreased posttransplant hospital length of stay.

Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution for organ preservation in clinical pancreas transplantation.

Background. University of Wisconsin (UW) solution is currently the standard preservation solution used for abdominal organ transplantation. This study assesses the efficacy of histidine-tryptophan-ketoglutarate (HTK) compared with UW in pancreas transplantation. Methods. Between October 2002 and August 2003, 20 pancreas transplants were performed. Patients were divided into two groups: UW (n=10) and HTK (n=10). Donor and recipient demographics were similar in both groups. The mean cold ischemia time for both groups was 11±3 hr. Results. There was an anticipated difference between total preservative volumes used (HTK: 4.5±1.2 L vs. UW: 3.4±0.8 L; P =0.03). Patient and graft survivals to date were 100% in both groups. Serum fasting blood glucose, peak amylase, and serial amylase levels remained comparable at all intervals posttransplantation. Conclusions. Within this range of cold ischemia time, UW and HTK demonstrate similar efficacy in pancreas preservation.

Complications after a 5-year experience with laparoscopic donor nephrectomy: the Indiana University experience.

BackgroundLaparoscopic donor nephrectomy (LDN) is becoming the standard of care for living donor nephrectomy. However, questions have been raised about the safety of LDN for the donor and about the potentially increased rates for ureteral complications experienced by the recipient. In this report, the authors review their 5-year experience with 253 living laparoscopic donor nephrectomies.MethodsA retrospective chart review was performed for 253 laparoscopic live donors. Graft function and survival were compared using recipient postoperative creatinine values up to 12 months.ResultsThe overall rate of complications in the investigated series was 10.3%. There were seven intraoperative complications (2.8%), three of which required open conversion. There were 19 postoperative complications (7.5%), three of which required reexploration for bleeding. The majority of complications were minor including 62% grade 1, 8% grade 2, 31% grade 3, and no grade 4 or 5 complications. There were no intraoperative complications in the right-sided donor group. There was a 5% complication rate for patients with a body mass index (BMI) exceeding 25. The findings showed that 11.2% of the recipients had slow graft function, and 4.4% had delayed graft function. Less than 1% of the recipients experienced ureteral stricture requiring permanent stent placement or reoperation. Overall, there was a 2% graft loss rate.ConclusionsThe findings show a low rate of intraoperative and postoperative complications, most of which were minor complications. There was an increase in operative time and hospital stay in the right-sided group, but no increase in complication rate. There was no significant difference in outcome or complication rate for the overweight patients.

Steroid withdrawal for pancreas after kidney transplantation in recipients on maintenance prednisone immunosuppression.

Steroid withdrawal from patients taking prednisone for their renal allograft at the time of reinduction of immunosuppression for subsequent pancreas after kidney (PAK) transplantation has not been explored. Our expectation was that lymphocyte depletion, in conjunction with an augmentation of immunosuppression at the time of pancreas transplantation would protect the recipient from rejection of the renal allograft when chronic maintenance steroids are withdrawn. Methods. Pancreas transplantation was performed using systemic venous drainage and enteric exocrine drainage. Regardless of preoperative immunosuppression, all patients received induction with antithymocyte globulin, a brief taper of intravenous solumedrol over four to five days, maintenance therapy with tacrolimus and sirolimus and either resumption of chronic maintenance steroids or complete withdrawal of steroids. Results. A total of 30 PAK transplants were performed in 29 recipients and divided into two groups: continuation of chronic steroids (n=10) or steroid-free (n=19). One pancreas allograft was lost and there was a single mortality in the steroid free group. There was no significant difference in renal function or incidence of infections. Conclusion. Steroids can be safely withdrawn following pancreas after kidney transplantation for recipients already on maintenance prednisone in the setting of rabbit antithymocyte globulin induction and tacrolimus and sirolimus maintenance immunosuppression.

The impact of a positive crossmatch upon outcome after liver transplantation

Recent reports have shown that liver allografts transplanted against a positive lymphocytotoxic crossmatch (CDC+) are susceptible to an increased frequency of rejection, and decreases in patient and graft survival. The implication of a positive flow cytometric crossmatch (FCXM+) in liver transplantation remains controversial. The purpose of this study was to determine what impact a pretransplant IgG crossmatch due to CDC+ or FCXM+ had upon the clinical outcome following liver transplantation. Preoperative crossmatch status was determined prospectively in 110 consecutive liver transplants performed between July 1991 and January 1995. Allografts were divided into three groups: negative crossmatch (NXM), positive flow cytometric crossmatch FCXM+, and positive lymphocytotoxic crossmatch CDC+. Crossmatch status did not impact patient or graft survival. Actuarial patient survival was similar between groups at 12 months (88% vs. 95% vs. 92%, NXM vs. FCXM+ vs. CDC+) and 24 months (81% vs. 93% vs. 92%, NXM vs. FCXM+ vs. CDC+) (P=0.1938). Actuarial allograft survival was similar between groups at 12 months (76% vs. 93% vs. 85%, NXM vs. FCXM+ vs. CDC+) and 24 months (76% vs. 89% vs. 85%, NXM vs. FCXM+ vs. CDC+) (P=0.0738). CDC+ allografts had a significant increase in early rejection episodes compared with NXM (46% vs. 7%, CDC+ vs. NXM) (P=0.003) or FCXM+ allografts (46% vs. 10%, CDC+ vs. FCXM+) (P=0.006). CDC+ allografts experienced significantly more rejection episodes per year than NXM (53% vs. 20%, CDC+ vs. NXM) (P=0.015) or FCXM+ allografts (53% vs. 23%, CDC+ vs. FCXM+) (P=0.02). CDC+ allografts had a significant increase in numbers of additional nonconventional therapeutic interventions compared to NXM allografts (0.9+/-0.5 vs. 0.2+/-0.1, CDC+ vs. NXM) (P=0.039). The presence of cytotoxic antibodies pretransplantation is associated with increased incidences of early rejection, and rejection episodes per year. With careful monitoring and aggressive therapeutic interventions the presence of cytotoxic antibodies are not deleterious to patient or liver allograft survival.

Comparison of pulsatile perfusion and cold storage for paired kidney allografts.

Use of pulsatile perfusion to optimize outcomes in deceased donor kidney transplantation remains controversial. This study is a retrospective analysis of all cadaveric renal allografts procured locally by our center over a 3-year period. Kidney pairs were identified in which one kidney underwent pulsatile perfusion and transplantation at our center, whereas the contra-lateral kidney underwent cold storage and transplantation at another center. Eighty-eight percent of the exported kidneys were six-antigen matches. Study outcomes included 1-year graft and patient survival, delayed graft function, and need for posttransplant dialysis. Recipients had similar demographic and disease characteristics. Survival for pulsatile perfusion and cold storage were 95% and 88% (graft, P=0.43) and 98% and 90% (patient, P=0.36), respectively. The incidence of delayed graft function was 5% and 35% (P<0.01), whereas posttransplant dialysis was 5% and 30% (P<0.01), for pulsatile perfusion and cold storage, respectively. These data support routine use of pulsatile perfusion.

The strength of donor-specific antibody is a more reliable predictor of antibody-mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.

Mujtaba MA, Goggins W, Lobashevsky A, Sharfuddin AA, Yaqub MS, Mishler DP, Brahmi Z, Higgins N, Milgrom MM, Diez A, Taber T. The strength of donor‐specific antibody is a more reliable predictor of antibody‐mediated rejection than flow cytometry crossmatch analysis in desensitized kidney recipients.
Clin Transplant 2011: 25: E96–E102.

Analysis of anti-HLA antibodies in sensitized kidney transplant candidates subjected to desensitization with intravenous immunoglobulin and rituximab.

Background Preexisting donor-specific antibodies against human leukocyte antigens are major risk factors for acute antibody-mediated and chronic rejection of kidney transplant grafts. Immunomodulation (desensitization) protocols may reduce antibody concentration and improve the success of transplant. We investigated the effect of desensitization with intravenous immunoglobulin and rituximab on the antibody profile in highly sensitized kidney transplant candidates. Methods In 31 transplant candidates (calculated panel-reactive antibody [cPRA], 34%–99%), desensitization included intravenous immunoglobulin on days 0 and 30 and a single dose of rituximab on day 15. Anti–human leukocyte antigen antibodies were analyzed before and after desensitization. Results Reduction of cPRA from 25% to 50% was noted for anti–class I (5 patients, within 20–60 days) and anti–class II (3 patients, within 10–20 days) antibodies. After initial reduction of cPRA, the cPRA increased within 120 days. In 24 patients, decrease in mean fluorescence intensity of antibodies by more than 50% was noted at follow-up, but there was no reduction of cPRA. Rebound occurred in 65% patients for anti–class I antibodies at 350 days and anti–class II antibodies at 101 to 200 days. Probability of rebound effect was higher in patients with mean fluorescence intensity of more than 10,700 before desensitization, anti–class II antibodies, and history of previous transplant. Conclusions The desensitization protocol had limited efficacy in highly sensitized kidney transplant candidate because of the short period with antibody reduction and high frequency of rebound effect.

Subtypes of immunoglobulin (Ig)-G antibodies against donor class II HLA and cross-match results in three kidney transplant candidates

Preexisting donor-specific antibodies (DSA) play a critical role in the success of solid-organ transplantation. Cross-match (CM) between donor lymphocytes and recipient serum is a pivotal methodology for detecting these antibodies. Luminex platform based solid-phase methodology for anti-human leukocyte antigen (HLA) antibody analysis has revolutionized the approach to antibody detection and HLA specificity identification. In this study, we have reported three cases of successful living donor kidney transplantations performed against strongly positive B lymphocyte flow cytometry (FC) CM owing to highly reactive DSA directed to HLA class II. IgG solid-phase subtype analysis showed that more than 50% of these antibodies were represented by non-complement binding IgG2/IgG4 subtypes. These findings account for antibody mediated rejection (AMR) free long-term post-transplant course in these patients despite, the high level of DSA. Thus, we conclude that routine application of single HLA-coated beads (SAB) IgG subtype assay may provide new insights regarding transplantation or desensitization of patients presenting with negative B-cell complement dependent cytotoxic (CDC) and positive FC CM.

Staged Nephrectomy Versus Bilateral Laparoscopic Nephrectomy in Patients With Autosomal Dominant Polycystic Kidney Disease

PURPOSE In patients with autosomal dominant polycystic kidney disease we compared the outcome of bilateral laparoscopic nephrectomy at a single operation vs staged nephrectomy, including 1 during transplantation and the other via laparoscopic unilateral nephrectomy. MATERIALS AND METHODS We reviewed the records of patients with autosomal dominant polycystic kidney disease requiring renal transplantation and native bilateral nephrectomy. We compared transplantation with ipsilateral nephrectomy to transplantation alone and then compared unilateral to bilateral laparoscopic native nephrectomy. Indications included pain, infection, bleeding and compressive symptoms. RESULTS We followed 42 patients, including 16 with transplantation and nephrectomy, 22 with transplantation alone and 4 awaiting transplantation. In those with transplantation vs transplantation with nephrectomy there were no differences in median age (48.3 vs 53.3 years, p = 0.178) or greatest kidney length (19.5 vs 20.9 cm, p = 0.262). Operative time (208 vs 236 minutes, p = 0.104), estimated blood loss (200 vs 250 ml, p = 0.625), hospital discharge creatinine (1.60 vs 1.50 mg/dl, p = 0.491) and complications were similar. We separately compared 24 bilateral and 18 unilateral laparoscopic native nephrectomies, and noted similarities in median age (52.0 vs 56.3 years, p = 0.281) and kidney length (19.5 vs 19.8 cm, p = 0.752). Bilateral nephrectomy showed greater estimated blood loss (125 vs 50 ml, p = 0.001) and operative time (302.8 vs 170.2 minutes, p <0.001). There were 4 open conversions, 9 perioperative complications at bilateral surgery and 1 complication after unilateral surgery. Median followup in the unilateral and bilateral groups was 13.3 vs 35.9 months (p = 0.015). CONCLUSIONS Renal transplantation and ipsilateral native nephrectomy carry no significant additional morbidity compared to that of renal transplantation alone. Staged unilateral laparoscopic nephrectomy was superior to the bilateral procedure in perioperative outcome.