David B. Leeser

Comparison of laparoendoscopic single-site donor nephrectomy and conventional laparoscopic donor nephrectomy: donor and recipient outcomes.

OBJECTIVE To present a comparison of perioperative donor outcomes and recipient graft function in a series of patients undergoing laparoendoscopic single-site donor nephrectomy (LESS-DN) versus conventional laparoscopic donor nephrectomy (LDN). METHODS Data were collected for 50 consecutive LESS-DN patients and a matched cohort of 50 LDN patients. The donor outcomes analyzed included operative time, estimated blood loss, complications, visual analog pain scores, and recovery time. The recipient outcomes analyzed included serum creatinine at discharge and follow-up and the incidence of delayed graft function. RESULTS The mean total operative time was shorter in the LDN group than in the LESS-DN group (P < .0001). Linear regression analysis of the LESS-DN operative times relative to case number showed a significant decrease in the operative time with increasing case number (r(2) = 0.19, P = .002). No statistically significant differences were found in estimated blood loss, warm ischemia time, length of stay, or visual analog pain scores between the 2 groups. However, the surgical incision was significantly smaller in the LESS-DN group (P < .0001). After discharge, the patient-reported time to complete recovery was faster in the LESS-DN group (P = .01). The incidence of complications was similar in both groups; however, major complications only occurred in the LDN group. No differences were found in the recipient serum creatinine values or the incidence of delayed graft function. CONCLUSION Our initial experience with LESS-DN is encouraging. This retrospective matched-pair comparison between LESS-DN and LDN suggests that the single-port approach might be associated with quicker convalescence. Longer operative times in the LESS-DN group could simply represent the learning curve of a novel procedure.

Chain Transplantation: Initial Experience of a Large Multicenter Program

We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross‐matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O‐patients receiving a transplant (n = 90) was greater than the number of blood type O‐non‐directed donors (n = 32) initiating chains. We have 1‐year follow up on the first 100 transplants. The mean 1‐year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.

Laparoendoscopic Single Site Live Donor Nephrectomy: Initial Experience

PURPOSE We present our initial experience in 40 patients undergoing laparoendoscopic single site donor nephrectomy. MATERIALS AND METHODS We prospectively collected data on 40 consecutive patients. A single access GelPOINT™ device was inserted into the abdomen through a 4 to 5 cm periumbilical incision. We used a bariatric camera with a right angle attachment for the light cord to maximize triangulation. Parameters analyzed included warm ischemia time, operative time, estimated blood loss, visual analog pain score, time to recipient creatinine less than 3 mg/dl, and recipient creatinine at discharge home, and 3 and 6 months. RESULTS A total of 38 left and 2 right donor nephrectomies were performed. Complete laparoendoscopic single site donor nephrectomy was successful in 38 cases. One left and 1 right case were converted to a hand assisted approach. Average ± SD body mass index was 26.1 ± 5.2 kg/m(2). Mean operative time to allograft extraction was 93.5 ± 27.5 minutes and mean total operative time was 166.7 ± 33.8 minutes. Average estimated blood loss was 106.7 ± 93.5 cc. Mean warm ischemia time was 3.96 ± 0.72 minutes. Mean hospital stay was 1.77 ± 0.43 days and median time to recipient creatinine less than 3.0 mg/dl was 54.2 ± 110.3 hours. Mean recipient creatinine at discharge home, and at 3 and 6 months was 1.48 ± 0.67, 1.29 ± 0.38 and 1.19 ± 0.34 mg/dl, respectively. Complications included hyponatremia in 1 patient, wound infection in 1, and a grade III laceration in an allograft that was sustained during extraction. CONCLUSIONS Our initial experience with laparoendoscopic single site donor nephrectomy is encouraging. This approach to kidney donation without an extra-umbilical incision could become particularly relevant to minimize morbidity in young, healthy organ donors.

Obesity following kidney transplantation and steroid avoidance immunosuppression.

Abstract:  Obesity is an important co‐morbidity within end‐stage renal disease (ESRD) and renal transplant populations. Previous studies have suggested that chronic corticosteroids result in increased body weight post‐transplant. With the recent adoption of steroid‐sparing immunosuppressive strategies, we evaluated the effect of these strategies on body mass index (BMI) after renal transplantation. We examined 95 renal transplant recipients enrolled in National Institutes of Health clinical transplant trials over the past three yr who received either lymphocyte depletion‐based steroid sparing or traditional immunosuppressive therapy that included steroids for maintenance immunosuppression. Recipients were overweight prior to transplant and no significant differences existed in pre‐transplant BMI among treatment groups. Regardless of therapy, BMI increased post‐transplant in all recipients. The BMI increase consisted of an average weight gain of 5.01 ± 7.12 kg (mean, SD) post‐transplant. Additionally, in a number of recipients placed on maintenance steroids, subsequent withdrawal at a mean of 100 d post‐transplant had no impact on weight gain. Thus, body weight and BMI increase following kidney transplantation, even in the absence of steroids. Thus, patients gain weight after renal transplantation regardless of the treatment strategy. Steroid avoidance alone does not reduce risk factors associated with obesity in our patient population.

Kidney Transplant Chains Amplify Benefit of Nondirected Donors

IMPORTANCE Despite the potential for altruistic nondirected donors (NDDs) to trigger multiple transplants through nonsimultaneous transplant chains, concerns exist that these chains siphon NDDs from the deceased donor wait list and that donors within chains might not donate after their partner receives a transplant. OBJECTIVE To determine the number of transplantations NDDs trigger through chains. DESIGN Retrospective review of large, multicenter living donor-recipient database. SETTING Fifty-seven US transplant centers contributing donor-recipient pairs to the database. PARTICIPANTS The NDDs initiating chain transplantation. MAIN OUTCOMES MEASURE Number of transplants per NDD. RESULTS Seventy-seven NDDs enabled 373 transplantations during 46 months starting February 2008. Mean chain length initiated by NDDs was 4.8 transplants (median, 3; range, 1-30). The 40 blood type O NDDs triggered a mean chain length of 6.0 (median, 4; range, 2-30). During the interval, 66 of 77 chains were closed to the wait list, 4 of 77 were ongoing, and 7 of 77 were broken because bridge donors became unavailable. No chains were broken in the last 15 months, and every recipient whose incompatible donor donated received a kidney. One hundred thirty-three blood type O recipients were transplanted. CONCLUSION AND RELEVANCE This large series demonstrates that NDDs trigger almost 5 transplants on average, more if the NDD is blood type O. There were more blood type O recipients than blood type O NDDs participating. The benefits of transplanting 373 patients and enabling others without living donors to advance outweigh the risk of broken chains that is decreasing with experience. Even 66 patients on the wait list without living donors underwent transplantation with living-donor grafts at the end of these chains.

Generation and Functional Capacity of Polyclonal Alloantigen-Specific Memory CD4 T Cells

Alloreactive memory T cells can significantly impact graft survival due to their enhanced functional capacities, diverse tissue distribution and resistance to tolerance induction and depletional strategies. However, their role in allograft rejection is not well understood primarily due to the lack of suitable in vivo models. In this study, we use a novel approach to generate long‐lived polyclonal alloreactive memory CD4 T cells from adoptive transfer of alloantigen‐activated precursors into mouse hosts. We demonstrate that CD25 upregulation is a marker for precursors to alloantigen‐specific memory and have created a new mouse model that features an expanded population of polyclonal alloreactive memory T cells that is distinguishable from the naive T‐cell population. Furthermore, we show that alloreactive memory T cells exhibit rapid recall effector responses with predominant IFN‐γ and IL‐2 production, and mediate vigorous allograft rejection. Interestingly, while we found a heterogeneous distribution of allomemory T cells in lymphoid and nonlymphoid tissues, they were all predominantly of the effector‐memory (CD62Llo) phenotype. Our results present a unique model for the generation and tracking of polyclonal allospecific memory CD4 T cells in vivo and reveal insights into the distinct and robust nature of alloreactive T‐cell memory.

Pancreas transplantation considering the spectrum of body mass indices

Afaneh C, Rich B, Aull MJ, Hartono C, Kapur S, Leeser DB. Pancreas transplantation considering the spectrum of body mass indices. 
Clin Transplant 2011: 25: E520–E529.

Probabilistic (Bayesian) Modeling of Gene Expression in Transplant Glomerulopathy

Transplant glomerulopathy (TG) is associated with rapid decline in glomerular filtration rate and poor outcome. We used low-density arrays with a novel probabilistic analysis to characterize relationships between gene transcripts and the development of TG in allograft recipients. Retrospective review identified TG in 10.8% of 963 core biopsies from 166 patients; patients with stable function were studied for comparison. The biopsies were analyzed for expression of 87 genes related to immune function and fibrosis by using real-time PCR, and a Bayesian model was generated and validated to predict histopathology based on gene expression. A total of 57 individual genes were increased in TG compared with stable function biopsies (P < 0.05). The Bayesian analysis identified critical relationships between ICAM-1, IL-10, CCL3, CD86, VCAM-1, MMP-9, MMP-7, and LAMC2 and allograft pathology. Moreover, Bayesian models predicted TG when derived from either immune function (area under the curve [95% confidence interval] of 0.875 [0.675 to 0.999], P = 0.004) or fibrosis (area under the curve [95% confidence interval] of 0.859 [0.754 to 0.963], P < 0.001) gene networks. Critical pathways in the Bayesian models were also analyzed by using the Fisher exact test and had P values <0.005. This study demonstrates that evaluating quantitative gene expression profiles with Bayesian modeling can identify significant transcriptional associations that have the potential to support the diagnostic capability of allograft histology. This integrated approach has broad implications in the field of transplant diagnostics.

HIV-infected kidney graft recipients managed with an early corticosteroid withdrawal protocol: clinical outcomes and messenger RNA profiles.

Background The outcome of HIV-infected kidney transplant recipients managed with an early corticosteroid withdrawal protocol is not known. Methods Eleven consecutive HIV-infected patients with undetectable plasma HIV RNA and more than 200/mm3 CD4+ T cells underwent deceased-donor (n=8) or living-donor (n=3) kidney transplantation at our center. All were managed with an early corticosteroid withdrawal protocol; 9 of 11 received antithymocyte globulin and 2 received basiliximab induction. We analyzed patient and graft outcomes, acute rejection rate, HIV progression, BKV replication, infections, and urinary cell mRNA profiles. Results The median (range) follow-up was 44.5 (26–73) months. The incidence of acute rejection was 9% at 1 year and the patient and allograft survival rates were 100% and 91%, respectively. Estimated glomerular filtration rate at 1 year (mean±SD) was 78±39 mL/min/1.73 m2. Plasma HIV RNA was undetectable at 24 months and none had BKV replication. Six of the 11 kidney recipients developed eight infections requiring hospitalization. Urinary cell levels of mRNA for complement components and complement regulatory proteins, cell lineage–specific proteins CD3, CD4, CD8, CTLA4, Foxp3, chemokine IP-10, cytotoxic perforin and granzyme B, and BKV VP1 mRNA were not different (P>0.05) between HIV-infected patients and HIV-negative recipients (n=22) with stable graft function and normal biopsy results. Conclusion An early steroid withdrawal regimen with antithymocyte globulin induction was associated with excellent graft and patient outcomes in HIV-infected recipients of kidney allografts. Their urinary cell mRNA profiles are indistinguishable from those of HIV-negative patients with stable graft function and normal biopsy results.

Live Donor Renal Transplant With Simultaneous Bilateral Nephrectomy for Autosomal Dominant Polycystic Kidney Disease Is Feasible and Satisfactory at Long-term Follow-up.

Background Timing of bilateral nephrectomy (BN) is controversial in patients with refractory symptoms of autosomal dominant polycystic kidney disease (APKD) in need of a renal transplant. Methods Adults who underwent live donor renal transplant (LRT) + simultaneous BN (SBN) from August 2003 to 2013 at a single transplant center (n = 66) were retrospectively compared to a matched group of APKD patients who underwent LRT alone (n = 52). All patients received general health and polycystic kidney symptom surveys. Results Simultaneous BN increased operative duration, estimated blood loss, transfusions, intravenous fluid, and hospital length of stay. Most common indications for BN were pain, loss of abdominal domain, and early satiety. There were more intraoperative complications for LRT + SBN (6 vs 0, P = 0.03; 2 vascular, 2 splenic, and 1 liver injury; 1 reexploration to adjust graft positioning). There were no differences in Clavien-Dindo grade I or II (39% vs 25%, P = 0.12) or grade III or IV (7.5% vs 5.7%, P = 1.0) complications during the hospital course. There were no surgery-related mortalities. There were no differences in readmission rates (68% vs 48%, P = 0.19) or readmissions requiring procedures (25% vs. 20%, P = 0.51) over 12 months. One hundred percent of LRT + SBN allografts functioned at longer than 1 year for those available for follow-up. Survey response rate was 40% for LRT-alone and 56% for LRT + SBN. One hundred percent of LRT + SBN survey responders were satisfied with their choice of having BN done simultaneously. Conclusions Excellent outcomes for graft survival, satisfaction, and morbidity suggest that the combined operative approach be preferred for patients with symptomatic APKD to avoid multiple procedures, dialysis, and costs of staged operations.