Alvin Wee

A systematic approach to minimizing wound problems for de novo sirolimus-treated kidney transplant recipients.

Background. Wound healing problems and lymphoceles have been reported with greater frequency in kidney recipients given de novo sirolimus. This problem has led to increased patient morbidity and cost; and has been an impediment to the completion of randomized controlled trials in which wound problems have necessitated premature discontinuation of mammalian target of rapamycin inhibitors. Methods. We developed a systematic program to reduce these problems based on patient selection (body mass index [BMI] <32 kg/m2), the use of closed suction drains, modifications of surgical technique, and avoidance of a loading dose of sirolimus. Consecutive series of adult kidney-only recipients given antibody induction followed by de novo sirolimus, mycophenolate mofetil, and steroids were compared; group 1: 204 patients transplanted with few restrictions and group 2: 103 patients transplanted using the above program. Results. This approach resulted in a significant reduction (group 2 vs. group 1) in cumulative wound complications (7.8% vs. 19.6%, P=0.007), and nonoperative wound complications (2.9% vs. 14.2%, P=0.001). In addition, the incidence of lymphoceles detected (22.3% vs. 47.1%, P<0.0001), treated (4.8% vs. 24.5%, P<0.0001), or needing surgical intervention (1.9% vs. 14.2%, P=0.001) was significantly reduced. Multivariate analysis demonstrated that a BMI more than 30 to 32 kg/m2 was the most significant variable related to delayed wound healing (odds ratio [OR] 3.01, 0.02) or surgical repair (OR 8.05, P=0.0001), whereas BMI (OR 1.54, P=0.038) and acute rejections (OR 1.34, P=0.03) were most associated with lymphocele treatment. Conclusions. A systematic program of wound care using de novo sirolimus can produce wound healing complications comparable with that reported with other agents.

Nomograms for Predicting Graft Function and Survival in Living Donor Kidney Transplantation Based on the UNOS Registry

PURPOSE We developed nomograms that predict transplant renal function at 1 year (Modification of Diet in Renal Disease equation [estimated glomerular filtration rate]) and 5-year graft survival after living donor kidney transplantation. MATERIALS AND METHODS Data for living donor renal transplants were obtained from the United Network for Organ Sharing registry for 2000 to 2003. Nomograms were designed using linear or Cox regression models to predict 1-year estimated glomerular filtration rate and 5-year graft survival based on pretransplant information including demographic factors, immunosuppressive therapy, immunological factors and organ procurement technique. A third nomogram was constructed to predict 5-year graft survival using additional information available by 6 months after transplantation. These data included delayed graft function, any treated rejection episodes and the 6-month estimated glomerular filtration rate. The nomograms were internally validated using 10-fold cross-validation. RESULTS The renal function nomogram had an r-square value of 0.13. It worked best when predicting estimated glomerular filtration rate values between 50 and 70 ml per minute per 1.73 m(2). The 5-year graft survival nomograms had a concordance index of 0.71 for the pretransplant nomogram and 0.78 for the 6-month posttransplant nomogram. Calibration was adequate for all nomograms. CONCLUSIONS Nomograms based on data from the United Network for Organ Sharing registry have been validated to predict the 1-year estimated glomerular filtration rate and 5-year graft survival. These nomograms may facilitate individualized patient care in living donor kidney transplantation.

Beneficial Outcomes of a Steroid-Free Regimen With Thymoglobulin Induction in Pancreas-Kidney Transplantation

BACKGROUND Steroid-free immunosuppressive regimens are becoming more common in pancreas transplantation, with persistent concerns regarding its safety and efficacy. METHODS We performed a retrospective chart review of 87 pancreas transplant recipients-22 simultaneous pancreas-kidney transplants, 48 pancreas-after-kidney transplants, and 17 pancreas transplant alone-who underwent transplantation within the period of January 2000 to November 2006 and who received induction therapy with thymoglobulin followed by maintenance immunosuppression with tacrolimus and mycophenolate mofetil. We compared one group on a steroid-free regimen (n = 25) with another on a steroid-based regimen (n = 62). RESULTS At 6 months, there was no kidney graft loss and no significant difference between groups (steroid-free vs steroid-based groups) in patient survival (100% vs 96.8%), pancreas graft survival (96.0% vs 93.5%), acute rejection (4.0% vs 11.3%), hospitalization for any cause (60.0% vs 51.6%), infection requiring hospitalization (16.0% vs 32.3%), or incidence of BK viremia (0% vs 3.2%). CMV viremia occurred less in the steroid-free group (0% vs 17.7% in the steroid-based group, P = .024). The estimated glomerular filtration rate (eGFR) at 6 months was higher in the steroid-free group (74.8 vs 55.7 mL/min/1.73 m2 in the steroid-based group, P = .001), with fewer occurrences of a 25% decline in eGFR (33.3% among the steroid-free group vs 61.7% among steroid-based group, P = .019), despite similar average tacrolimus exposure (11.7 +/- 3.7 vs 12.2 +/- 2.7 ng/dL, P = .478). CONCLUSIONS A steroid-free regimen with thymoglobulin induction followed by tacrolimus and mycophenolate mofetil for maintenance in pancreas transplantation was safe and effective in preventing rejection, with reduced incidence of CMV infection and better-preserved kidney function.

Duodenoduodenostomy in pancreas transplantation.

Gunasekaran G, Wee A, Rabets J, Winans C, Krishnamurthi V. Duodenoduodenostomy in pancreas transplantation.

The use of bovine pericardium for complex urologic venous reconstruction.

OBJECTIVE To describe the use of bovine pericardium (BP) in several scenarios for venous patching and as a tubularized graft in urologic surgery. METHODS BP was used as patch or tubularized graft in 7 patients between 2010 and 2013. Clinical scenarios and operative indications were reviewed. We used BP as a patch graft for the inferior vena cava (IVC) (N = 3) and for the iliac venous system (N = 1) to restore venous outflow. Tubularized grafts were used (N = 2) to replace the left renal vein in oncology procedures and during renal autotransplantation (N = 1). Surgical technique is reviewed in detail. RESULTS We used BP as a venous patching in 4 cases and as a tubularized graft in 3 cases. There was no evidence of venous thrombosis of the replaced system with a mean of 14.8 months (range, 9-26) follow-up. CONCLUSION The use of BP as a patch or tubularized graft is an option for complicated urologic venous reconstruction. Although the follow-up interval is relatively short and this initial series small, our initial results are promising.

Pancreas Transplantation: Surgical Techniques

Successful pancreas transplantation demands meticulous attention to surgical techniques. This chapter covers the commonly employed surgical techniques used in pancreas transplantation. The authors present a framework for practice that draws on both their experience and a critical review of available literature.

Simultaneous versus Pretransplant Native Nephrectomy in Autosomal Dominant Polycystic Kidney Disease Patients

Introduction 50% of autosomal dominant polycystic kidney disease (ADPKD) patients will develop ESRD. For those patients who undergo renal transplantation (RT) and require a native nephrectomy (NN), the optimal timing of NN in relation to RT remains unknown. Materials and Methods We retrospectively reviewed 216 adult patients who underwent RT for ADPKD from 2005 to 2017. Patients were stratified by timing of NN into 2 groups. Group 1 included patients who had simultaneous NN and RT (n=102) & Group 2 underwent NN prior to RT (n=26). Patients with post-transplant NN (n=5) and those not requiring NN (n=83) were excluded, leaving 128 patients for analysis. Data were analyzed with chi-squared or Mann-Whitney U test. Results The median age for both groups was 52 (p=0.943) and 55% were male (p=0.095). Regarding co-morbidities, 8/128 (6%) had DM at the time of transplant and 119/128 (93%) had HTN (p=0.696, 0.116, respectively). 36% of patients were symptomatic. The most common symptom was pain (25/46). Non-symptomatic patients underwent NN when the native kidney extended into the pelvis. Group 1 patients were more likely to be preemptive (47% vs. 0% [p<0.0001]) and receive living donors (58% vs 29% [p=0.007]). Median EBL for Group 1 was 500 ml (IQR 300-900) vs 200 (IQR 150-388) for Group 2 (p<0.0001). Median operative time for transplant was 458 min (IQR 351-565) for Group 1 vs. 363 min (IQR 289-410) for Group 2 (p=0.034). There were no differences in intraoperative complications (total rate 5.5%, p=0.169) or in postoperative complications (20%, p=0.094). The most frequent post-op complication was ileus (28%). Median length of stay was 6 days for both groups (p=0.268) and there was no difference in the readmission rate (p=0.81). The most frequent reason for readmission overall was infection (22%). Median creatinine (Cr) at discharge was 1.7 (IQR 1.2-3.1) for Group 1 vs 2.5 (IQR 1.6-4.6) for Group 2 (p=0.027). Creat one year was 1.6 (IQR 1.3-2.1) for Group 1 vs 1.4 (IQR 1.2-1.8) for Group 2 (p=0.110) for patients transplanted prior to 11/2016. Conclusions Patients who underwent simultaneous NN and KT experienced lower immediate post-op Cr which can likely be explained by the increased rate of living donor transplantation in this group. However, the difference in Cr disappeared within 1 year and there were no differences in perioperative complications. Our results indicate that simultaneous surgery is safe despite longer operative times and greater blood loss and that the two approaches have similar 1-year short-term outcomes. Timing decisions should be based on individual patient circumstances and patient & surgeon preference.

Dramatic secular changes in prognosis for kidney transplant candidates in the United States

Over recent decades, numerous clinical advances and policy changes have affected outcomes for candidates of kidney transplantation in the United States. We examined the national Scientific Registry for Transplant Recipients for adult (18+) solitary kidney transplant candidates placed on the waiting list for primary listing from 2001 to 2015. We evaluated rates of mortality, transplantation, and waitlist removal. Among 340 115 candidates there were significant declines in mortality (52 deaths/1000 patient years in 2001‐04 vs 38 deaths/1000 patient years in 2012‐15) and transplant rates (304 transplants/1000 patient years in 2001‐04 vs 212 transplants/1000 patient years in 2012‐15) and increases in waitlist removals (15 removals/1000 patient years in 2001‐04 vs 25/1000 patient years in 2012‐15) within the first year after listing. At 5 years an estimated 37% of candidates listed in 2012‐15 were alive without transplant as compared to 22% in 2001‐04. Declines in mortality over time were significantly more pronounced among African Americans, candidates with longer dialysis duration, and those with diabetes (P < .001). Cumulatively, results indicate dramatic changes in prognoses for adult kidney transplant candidates, likely impacted by selection criteria, donor availability, regulatory oversight, and clinical care. These trends are important considerations for prospective policy development and research, clinical and patient decision‐making, and evaluating the impact on access to care.

The Clinical Relevance of HLA Cw, DQ and DP Mismatches Among The Zero HLA A, B and DR Mismatched Deceased Donor (DD) Kidney Transplant Population.: Abstract# 2245

2244 Reduction of Proteinuria With Selective Vitamin D Receptor Activation Using Paricalcitol in Renal Transplant Patients. M. Narasimhamurthy, F. Kamal, M. Igari, S. Natraj, R. Gohh. Kidney Disease and Hypertension, Warren Alpert Medical School of Brown University, Providence. Proteinuria after renal transplantation is associated with increased risk of graft loss, cardiovascular events and death. Paricalcitol, has shown to reduce proteinuria in both diabetic and nondiabetic nephropathies. However, little data exists regarding the use of Paricalcitol following renal transplantation. The purpose of this study is to determine if Paricalcitol results in proteinuria reduction in renal transplant patients and if it has any salutary effect on renal allograft function. Method: This is a prospective, double blinded, study of stable renal transplant recipients, at least 1 year post transplantation with an eGFR of ≥ 15 cc/min and urine spot protein-to-creatinine ratio (UPCR) of ≥ 0.5, who were randomized to receive either Paricalcitol (2 ug/day) or placebo for 6 months. Most patients in both arms received either tacrolimus or cyclosporine, mycophenolate and prednisone. 5/17 (29%) patients in the treatment arm received Sirolimus compared to 2/14 (14%) in the placebo arm. Angiotensin converting enzyme inhibitor or angiotensin receptor blocker was permitted but without dose changes during the trial. The Paricalcitol group had 17 patients (mean ± standard deviation of age: 46.4±13.7 years, serum creatinine (Cr): 2.0±0.6 mg/dl, UPCR: 1.7±1.4). The Placebo group had 14 patients (mean ± standard deviation of age: 59.2±10 years, serum Cr: 2.1±0.7mg/dl, UPCR: 2.1±2.0). UPCR and serum Cr were calculated monthly for 6 months for both groups. Results: Data were analyzed using growth mixed modeling with a lognormal link function using GLIMMIX/SAS Software 9.3. There was no signifi cant difference in serum Cr and UPCR at baseline between the Placebo and Paricalcitol groups (p=.82 and p=.24 respectively). The Paricalcitol group experienced a signifi cant decrease in UPCR of approximately 9% (p=.0014, 95% CI [3.8%, 14.2%]) for every month of treatment but showed a signifi cant increase in serum Cr of approximately 1.6% (p=.024, 95% CI [0.2%, 3.0%]) for every month. The placebo group did not experience any signifi cant change in either UPCR or serum Cr. Conclusion: Paricalcitol treatment resulted in a signifi cant reduction in proteinuria although with a signifi cant rise in serum Cr compared to placebo. By reducing proteinuria, Paricalcitol may have renoprotection in the setting of kidney transplantation, but this requires better assessment through a larger randomized trial. Abstract# 2245 The Clinical Relevance of HLA Cw, DQ and DP Mismatches Among The Zero HLA A, B and DR Mismatched Deceased Donor (DD) Kidney Transplant Population. N. Elfadawy,1 S. Flechner,1 A. Wee,1 P. Lalli,2 J. Schold,3 E. Poggio,1 B. Stephany,1 A. Gary,4 D. Thomas,4 M. Askar.4 1Glickman Urological and Kidney Institute, The Cleveland Clinic, Cleveland, OH; 2Histocompatibility and Flow Cytometry Laboratory, Carolinas Healthcare System, Charlotte, NC; 3Department of Quantitative Health Sciences, The Cleveland Clinic, Cleveland, OH; 4Allogen Laboratories, The Cleveland Clinic, Cleveland, OH. Background Zero HLA mismatch (0 MM) is UNOS defi ned as the absence of HLA serologic level mismatches at HLA-A, B, and DR antigens (Ag), and is known to result in better graft outcome after kidney transplantation. It is unclear whether mismatches at HLACw, DQ and DP would also have an independent impact on graft outcome. Methods In this retrospective study, 265 recipients who had shared 0MM DD kidney transplants at our center (1990 to 2012) were identifi ed and classifi ed into 2 groups. Group (A): HLA Cw, DQ and DP matched (n= 39, 15%) of which 20 patients were a perfect 12 Ag match and 19 patients were 12 Ag 0MM, and group (B) HLACw, DQ and DP mismatched (n=226, 85%) of which 107 patients were HLA A, B, DR 6 Ag matched, and 119 were HLA A, B, DR 0MM (< 6 Ag match). Long-term graft outcomes were compared between the 2 groups using time dependent survival model (Cox-model). Results The 2 groups were matched in terms of recipients’ age, gender, and race. In this study, 11.5% (n=26 patients) had biopsy proven acute cell-mediated rejection at any time after transplant (median 13, IQR 2.8-38 months), all in group B (p=0.002), with 5 patients developing DQ or DP donor specifi c antibodies (DSA). In addition, the 3, 5 and 10-year death censored graft survivals were signifi cantly better in group A (100, 97, and 87) compared to group B (92, 88, and 74 %) P=0.04. The 10 year patient survival was not signifi cantly different between the 2 groups (p = 0.6). Conclusion These results suggest that the majority of A, B, DR 0MM transplants are mismatched for Cw, DQ and/or DP. Moreover, HLACw, DQ and DP mismatches are clinically relevant and prospective typing and matching for these loci warrant further prospective investigation. Abstract# 2246 Longterm Outcomes of Re-Transplants Versus Primary Transplants: A Paired Analysis of the OPTN/UNOS Database. A. Khalil, T. Taber, M. Yaqub, D. Mishler, M. Mujtaba, N. Kassis, A. Sharfuddin. Medicine/ Nephrology & Transplant, Indiana University, Indianapolis, IN. 2246 Longterm Outcomes of Re-Transplants Versus Primary Transplants: A Paired Analysis of the OPTN/UNOS Database. A. Khalil, T. Taber, M. Yaqub, D. Mishler, M. Mujtaba, N. Kassis, A. Sharfuddin. Medicine/ Nephrology & Transplant, Indiana University, Indianapolis, IN. Background. Retransplantation has surgical and immunologic challenges that may lead to inferior outcomes compared to primary transplants. Methods. The outcomes of adult kidney re-transplant recipients (RTR) were compared to those receiving a fi rst transplant (FTR) from paired donor kidneys. The OPTN/UNOS database was used to identify deceased donors (n=6,266) who donated one kidney to a RTR and the mate kidney to a FTR between January 2000 to December 2010. All multi-organ transplants were excluded Results. As compared to FTR, RTR were younger (45 vs 52 years, p<0.001), had a longer dialysis vintage (869 vs 819 days, p<0.001), more sensitized (mean PRA 39% vs 13%, p<0.001) and higher proportion of PRA >80 (25% vs 7%, p<0.001). There were higher 0 mismatches in RTR (19% vs 16%, p<0.001), with mean mismatch level of 3.5 vs. 3.3, p<0.001.There was no signifi cant difference in gender distribution between the two groups; however, distribution of ethnicity differed signifi cantly (p<0.001) with more whites (57% vs 50%) in RTR group and lesser African Americans (27% vs 31%, p<0.001). There were more pre-emptive transplants in RTR (24% vs 21%, p=0.002). Delayed graft function (28% vs 25%, P=0.007) and a 1 year rejection rates (11% vs 9%, p<0.001) were higher in RTR. Death with functioning graft was lesser in RTR (12% vs 15%, p<0.001). Overall patient mortality was similar in FTR and RTR groups at 1 year (4.2% vs. 4.8%, p=0.135), 5 years (14.2% vs 13.6%, p=0.907) and 10 years (20.3% vs 18.3% p=0.111). The overall allograft failure rates were higher in RTR group compared to FTR group within 1 year (12.2% vs 8.9%, p<0.001), 5 years (29.1% vs 24.7%, p<0.001) and 10 years (36.7% vs 33.4%, p<0.001).