Meredith J. Aull

Improvement in Outcomes of Clinical Islet Transplantation: 1999–2010

OBJECTIVE To describe trends of primary efficacy and safety outcomes of islet transplantation in type 1 diabetes recipients with severe hypoglycemia from the Collaborative Islet Transplant Registry (CITR) from 1999 to 2010. RESEARCH DESIGN AND METHODS A total of 677 islet transplant-alone or islet-after-kidney recipients with type 1 diabetes in the CITR were analyzed for five primary efficacy outcomes and overall safety to identify any differences by early (1999–2002), mid (2003–2006), or recent (2007–2010) transplant era based on annual follow-up to 5 years. RESULTS Insulin independence at 3 years after transplant improved from 27% in the early era (1999–2002, n = 214) to 37% in the mid (2003–2006, n = 255) and to 44% in the most recent era (2007–2010, n = 208; P = 0.006 for years-by-era; P = 0.01 for era alone). C-peptide ≥0.3 ng/mL, indicative of islet graft function, was retained longer in the most recent era (P < 0.001). Reduction of HbA1c and resolution of severe hypoglycemia exhibited enduring long-term effects. Fasting blood glucose stabilization also showed improvements in the most recent era. There were also modest reductions in the occurrence of adverse events. The islet reinfusion rate was lower: 48% by 1 year in 2007–2010 vs. 60–65% in 1999–2006 (P < 0.01). Recipients that ever achieved insulin-independence experienced longer duration of islet graft function (P < 0.001). CONCLUSIONS The CITR shows improvement in primary efficacy and safety outcomes of islet transplantation in recipients who received transplants in 2007–2010 compared with those in 1999–2006, with fewer islet infusions and adverse events per recipient.

Epidemiology of BK virus in renal allograft recipients: independent risk factors for BK virus replication.

Background. Identification of risk factors for BK virus (BKV) replication may improve transplant outcome. We investigated the impact of immunosuppressive drugs on the prevalence of BKV replication in recipients of human renal allografts. Methods. One hundred twenty renal allograft recipients were studied prospectively at 1, 3, and 6 months posttransplantation to identify risk factors for BKV replication. BKV replication was quantified by measurement of urinary cell BKV VP1 mRNA levels using BKV specific primers and TaqMan probe in a real-time quantitative polymerase chain reaction assay. Levels of urinary cell mRNA for granzyme B, CD103, and transforming growth factor-β1 were measured to ascertain whether BKV replication is associated with an inflammatory signature. Results. The prevalence of BKV replication increased over time and was highest at 6 months compared with 1 or 3 months posttransplantation (P<0.001). A logistic regression model analysis demonstrated that steroid maintenance therapy (odds ratio: 8.3, P=0.003) and induction with rabbit anti-human thymocyte globulin (odds ratio: 5.8, P=0.008) were independent risk factors for BKV replication. Neither mycophenolate mofetil dose nor tacrolimus dose or trough levels were different between those with or without BKV replication. The development of acute rejection or antirejection treatment with methylprednisolone did not increase the risk of BKV replication. BKV replication was associated with heightened levels of urinary cell mRNA for granzyme B (P<0.002), CD103 (P<0.005) but not for transforming growth factor-β1 (P>0.05). Conclusions. Steroid maintenance therapy and induction with antithymocyte globulin are independent risk factors for BKV replication in renal allograft recipients treated with tacrolimus and mycophenolate mofetil.

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.

Characteristics of Circulating Donor Human Leukocyte Antigen-specific Immunoglobulin G Antibodies Predictive of Acute Antibody-mediated Rejection and Kidney Allograft Failure.

Background Characteristics of pretransplant antibodies directed at donor human leukocyte antigen (HLA) donor-specific antibodies (DSA) associated with adverse outcomes in kidney transplant recipients are being elucidated but uncertainties exist. Methods We prospectively screened pretransplant sera from 543 kidney recipients using single antigen bead assays and identified 154 patients with and 389 without DSA. We investigated the association of DSA features to acute rejection and graft failure. Results One-year acute rejection incidence was higher in DSA-positive group (P < 0.001), primarily due to antibody-mediated rejection (AMR, 13% vs. 1.8%, P < 0.001) and not T cell–mediated rejection (ACR, 5% vs.6%, P = 0.65). The sum of mean fluorescence intensity of DSA (DSA MFI-Sum) of 6,000 or higher (OR, 18; 95% CI, 7.0–47; P < 0.001) and the presence of DSA against both HLA class I and II (OR, 39; 95% CI, 14–106; P < 0.0001) predicted 1-year AMR, independent of other covariates. Calculated panel reactive antibody and a positive flow cytometry cross-match result were associated with AMR by bivariate analysis but neither was an independent predictor in a multivariable regression analysis that included DSA-MFI-Sum or HLA DSA class. In multivariable Cox proportional hazards models, the covariate-adjusted hazard ratio for graft failure was 2.03 (95%CI, 1.05–3.92; P = 0.04) for DSA MFI-Sum of 6,000 or higher and 2.23 (95% CI, 1.04–4.80; P = 0.04) for class I and II DSA. Prediction of graft failure was not independent of AMR. Conclusion Our study suggests that DSA MFI-Sum and HLA class of DSA are characteristics predictive of AMR and graft failure. The elevated risk of graft failure in those with the identified features of DSA is attributable to increased risk of AMR.

A Randomized, Prospective, Parallel Group Study of Laparoscopic Versus Laparoendoscopic Single Site Donor Nephrectomy for Kidney Donation

Few prospective, randomized studies have assessed the benefits of laparoendoscopic single site donor nephrectomy (LESS‐DN) over laparoscopic donor nephrectomy (LDN). Our center initiated such a trial in January 2011, following subjects randomized to LESS‐DN versus LDN from surgery through 5 years postdonation. Subjects complete recovery/satisfaction questionnaires at 2, 6 and 12 months postdonation; transplant recipient outcomes are also recorded. One hundred subjects (49 LESS‐DN, 51 LDN) underwent surgery; donor demographics were similar between groups, and included a predominance of female, living‐unrelated donors, mean age of 47 years who underwent left donor nephrectomy. Operative parameters (overall time, time to extraction, warm ischemia time, blood loss) were similar between groups. Conversion to hand‐assist laparoscopy was required in 3 LESS‐DN (6.1%) versus 2 LDN (3.9%; p = 0.67). Questionnaires revealed that 97.2% of LESS‐DN versus 79.5% of LDN (p = 0.03) were 100% recovered by 2 months after donation. No significant difference was seen in satisfaction scores between the groups. Recipient outcomes were similar between groups. Our randomized trial comparing LESS donor nephrectomy to LDN confirms that LESS‐DN offers a safe alternative to conventional LDN in terms of intra‐ and post‐operative complications. LDN and LESS‐DN offer similar recovery and satisfaction after donation.

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.

Successful Transplantation of Single Kidneys From Pediatric Donors Weighing Less Than or Equal to 10 kg Into Standard Weight Adult Recipients

Background. The outcomes of single kidneys transplanted from pediatric donors into standard adult recipients (>60 kg) are unknown. Furthermore, the outcomes of single kidneys transplanted from pediatric donors less than or equal to 10 kg are also unknown. Methods. We retrospectively compared 27 recipients of single kidneys from pediatric donors younger than or equal to 5 years with 69 recipients of adult cadaveric kidneys. Results. The mean pediatric kidney recipient weight was 69 kg. Two-year patient and graft survival in pediatric kidney recipients was 100% and 92.5% respectively, compared with 98.5% and 89.8% in adult kidney recipients (P=NS). Mean time (days) to achieve creatinine less than 3 mg/dL was 14±9 compared with 14±20 in adult kidney recipients (P=NS). Estimated glomerular filtration rate at discharge, 6, 12, 18, and 24 months was equivalent in both cohorts. Stratifying pediatric kidney recipients by donor weight, there were no differences in acute rejection or graft loss in recipients of kidney from donors less than or equal to 10 kg (n=11; mean weight=8.85 kg), but there was a higher incidence of delayed graft function (7 of 11 vs. 1 of 16; P=0.002). Estimated glomerular filtration rate at discharge, 6, 12, 18, and 24 months was equivalent in both cohorts. Conclusions. Single pediatric kidneys from donors younger than or equal to 5 years can be transplanted into standard adult recipients without compromising outcomes. Transplanting single kidneys from pediatric donors less than or equal to 10 kg into standard adult recipients is associated with an increased risk of delayed graft function; however, this does not compromise 2-year graft survival or function.

Pancreas Transplantation: Does Age Increase Morbidity?

Introduction. Pancreas transplantation (PTx) is the only definitive intervention for type 1 diabetes. Medical advancements in diabetes care have led to an aging PTx candidate pool. We report our experience with patients ≥50 years of age undergoing PTx. Methods. We reviewed 136 consecutive PTx patients at our institution from 1996–2010; 17 were ≥50 years of age. We evaluated demographics, surgical complications, acute rejection (AR) rates, nonsurgical infections, and survival outcomes. Results. Demographic data was similar (P > .05) between groups, excluding age. The two groups had comparable major and minor surgical complication rates (P = .10 and P = .25, resp.). The older group had a lower 1-year and overall AR rate (P = .04 and P = .03, resp.). The incidence of non-surgical infections and overall patient and graft survival was similar between groups (P > .05). Conclusion. Older patients with type 1 diabetes are feasible candidates for PTx, as surgical morbidity, incidence of infections, and AR rates are low.

Kidney Paired Donation and Its Potential Impact on Transplantation

This article updates the unique opportunities available to kidney transplant candidates through kidney paired donation (KPD). KPD enables kidney transplant candidates with willing but incompatible living donors to enroll in a registry of other incompatible pairs to find a compatible transplant. Because of the ongoing shortage of deceased donor organs, KPD represents the most promising opportunity to increase the number of kidneys available for transplantation.

Sublingual Tacrolimus: A Pharmacokinetic Evaluation Pilot Study

To evaluate and compare the pharmacokinetic parameters of sublingual and oral tacrolimus in the presence and absence of a drug that interacts with tacrolimus at the intestinal level.