Linda J. Chen

Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of Simultaneous Pancreas–Kidney Transplants

Patients with type 1 diabetes (T1D) who are recipients of pancreas transplants are believed to rarely develop T1D recurrence in the allograft if effectively immunosuppressed. We evaluated a cohort of 223 recipients of simultaneous pancreas–kidney allografts for T1D recurrence and its risk factors. With long‐term follow‐up, recurrence was observed in approximately 7% of patients. Comparing the therapeutic regimens employed in this cohort over time, lack of induction therapy was associated with recurrence, but this occurs even with the current regimen, which includes induction; there was no influence of maintenance regimens. Longitudinal testing for T1D‐associated autoantibodies identified autoantibody positivity, number of autoantibodies, and autoantibody conversion after transplantation as critical risk factors. Autoantibodies to the zinc transporter 8 had the strongest and closest temporal association with recurrence, which was not explained by genetically encoded amino acid sequence donor–recipient mismatches for this autoantigen. Genetic risk factors included the presence of the T1D‐predisposing HLA‐DR3/DR4 genotype in the recipient and donor–recipient sharing of HLA‐DR alleles, especially HLA‐DR3. Thus, T1D recurrence is not uncommon and is developing in patients treated with current immunosuppression. The risk factors identified in this study can be assessed in the transplant clinic to identify recurrent T1D and may lead to therapeutic advances.

Pretransplant CD4 Count Influences Immune Reconstitution and Risk of Infectious Complications in Human Immunodeficiency Virus-Infected Kidney Allograft Recipients.

In current practice, human immunodeficiency virus–infected (HIV+) candidates with CD4 >200 cells/mm3 are eligible for kidney transplantation; however, the optimal pretransplant CD4 count above this threshold remains to be defined. We evaluated clinical outcomes in patients with baseline CD4 >350 and <350 cells/mm3 among 38 anti–thymocyte globulin (ATG)–treated HIV‐negative to HIV+ kidney transplants performed at our center between 2006 and 2013. Median follow‐up was 2.6 years. Rates of acute rejection and patient and graft survival were not different between groups. Occurrence of severe CD4 lymphopenia (<200 cells/mm3), however, was more common among patients with a baseline CD4 count 200–349 cells/mm3 compared with those transplanted at higher counts (75% vs. 30% at 4 weeks [p = 0.04] and 71% vs. 5% at 52 weeks [p = 0.001], respectively, after transplant). After adjusting for age, baseline CD4 count of 200–349 cells/mm3 was an independent predictor of severe CD4 lymphopenia at 4 weeks (relative risk [RR] 2.6; 95% confidence interval [CI] 1.3–5.1) and 52 weeks (RR 14.3; 95% CI 2–100.4) after transplant. Patients with CD4 <200 cells/mm3 at 4 weeks had higher probability of serious infections during first 6 months after transplant (19% vs. 50%; log‐rank p = 0.05). These findings suggest that ATG must be used with caution in HIV+ kidney allograft recipients with a pretransplant CD4 count <350 cells/mm3.

Impact of antiretroviral therapy on clinical outcomes in HIV+ kidney transplant recipients: Review of 58 cases

Background: Antiretroviral therapy (ART) poses challenging drug-drug interactions with immunosuppressant agents in transplant recipients. We aimed to determine the impact of specific antiretroviral regimens in clinical outcomes of HIV + kidney transplant recipients. Methods: A single-center, retrospective cohort study was conducted at a large academic center. Subjects included 58 HIV - to HIV + adult, first-time kidney transplant patients. The main intervention was ART regimen used after transplantation. The main outcomes assessed at one- and three-years were: patient survival, death-censored graft survival, and biopsy-proven acute rejection; we also assessed serious infections within the first six months post-transplant. Results: Patient and graft survival at three years were both 90% for the entire cohort. Patients receiving protease inhibitor (PI)-containing regimens had lower patient survival at one and three years than patients receiving PI-sparing regimens: 85% vs. 100% ( p=0.06) and 82% vs. 100% ( p=0.03), respectively. Patients who received PI-containing regimens had twelve times higher odds of death at 3 years compared to patients who were not exposed to PIs (odds ratio, 12.05; 95% confidence interval, 1.31-1602; p=0.02). Three-year death-censored graft survival was lower in patients receiving PI vs. patients on PI-sparing regimens (82 vs 100%, p=0.03). Patients receiving integrase strand transfer inhibitors-containing regimens had higher 3-year graft survival. There were no differences in the incidence of acute rejection by ART regimen. Individuals receiving PIs had a higher incidence of serious infections compared to those on PI-sparing regimens (39 vs. 8%, p=0.01). Conclusions: PI-containing ART regimens are associated with adverse outcomes in HIV + kidney transplant recipients.

Never events and hospital-Acquired conditions after kidney transplant

INTRODUCTIONnNever events (NE) and hospital-acquired conditions (HAC) after surgery have been designated as quality metrics in health-care by the Centres for Medicare and Medicaid Services (CMS).nnnMETHODSnThe Nationwide Inpatient Sample (NIS) database 2002-2012 was used to identify patientswho underwent kidney transplant. Multivariate analysis using logistic regression was used to identify outcomes and risk factors of HAC and NE after transplantation; however, we were limited by using a retrospective database missing some important variables specified for the kidney transplant, such as some operative factors, donor factors, and cold and warm ischemia times.nnnRESULTSnAmong 35 058 patients who underwent kidney transplant, there were 11 NEs, all of which were due to retained foreign bodies. Among HAC after surgery, falling was the most common (44.9%), followed by poor glycemic control (21.7%), vascular catheter-associated infection (21%), and catheter-associated urinary tract infection (8%). HAC and NE after surgery lead to a significant increase in mortality (adjusted odds ratio [AOR] 2.49; p=0.04), hospitalization length (13 vs. 7 days; p<0.01), and total hospital charges (

Renal Transplantation in a Patient With Unsuspected Inferior Vena Cava Obliteration.

231 801 vs.

Biomarkers in pancreas transplant

146 717; p<0.01). A significantly higher risk of HAC or NE was seen for patients who had more loss of function before surgey (AOR 3.25; p<0.01) and patients expected to have higher postoperative mortality before operation (AOR 1.62; p=0.03).nnnCONCLUSIONSnDespite the limitations of the study, we found HAC and NE significantly increase mortality, hospitalization length, and total hospital charges of kidney transplant patients. Quality improvement initiatives should target HAC and NE in order to successfully reduce or prevent these events.

A nationwide analysis of re-operation after kidney transplant

Abstract Vena cava thrombosis can represent a surgical challenge in the context of kidney transplantation. Selection of venous drainage in this setting should provide adequate venous outflow and minimize the risk of thrombosis and subsequent graft failure. We report the case of an adult female patient who presented for a deceased donor kidney transplant with incidental finding of complete inferior vena cava (IVC) and obliteration. After exploration of the retroperitoneal space up to the level of the obliterated IVC, a collateral venous branch was identified at the confluence of the right and left iliac veins. This was utilized as the site of the renal vein venous anastomosis. The patient recovered with immediate graft function. Follow-up ultrasound demonstrated patent vasculature without evidence of thrombosis or outflow obstruction. This report offers a surgical alternative to proceed in the case of an adult with unsuspected caval system obliteration.

PROLONGED COLD ISCHEMIA TIME BEFORE DOUBLE KIDNEY TRANSPLANTATION DOES NOT NEGATIVELY IMPACT ON OUTCOMES WHEN PRESERVED BY PULSATILE MACHINE PERFUSION.: 888

Purpose of reviewThe review analyzes the current biomarkers used in monitoring pancreas transplant, from the simple and time-tested, to more sophisticated, including markers of allo- and autoimmunity, that are likely to play a larger role in future studies. Recent findingsEvaluation of alloimmunity includes serum levels of donor-specific antibody, and, ultimately, pancreas transplant biopsies with C4d staining. Our center has focused on markers of autoimmunity, including assessment of autoantibodies and autoreactive T cells. We have found that conversion of autoantibodies (including GAD65, IA-2, and ZnT8), or the development of a new positive autoantibody, particularly ZnT8, are associated with type 1 diabetes (T1D) recurrence in the pancreas transplant. Autoreactive T cells have also been identified in the peripheral blood, pancreas transplant and peripancreas transplant–lymph nodes, that have the potential to mediate human &bgr;/islet cell destruction in vivo. SummaryThe monitoring of pancreas transplant biomarkers, particularly those associated with autoimmunity, has led to new insights into the pathogenesis of T1D. Progress in the elucidation of mechanisms of autoimmunity may lead to novel therapeutic approaches to both T1D recurrence of the pancreas transplant and perhaps also new onset T1D.

Combined Pancreas and En-Bloc Kidney Transplantation From Very Small Pediatric Donors.: Abstract# 749

INTRODUCTIONnWe aimed to report the rate and short-term outcomes of patients undergoing re-operation following kidney transplant in the U.S.nnnMETHODSnThe Nationwide Inpatient Sample (NIS) database was used to examine the clinical data of patients undergoing kidney transplant and re-operation during same the hospitalization from 2002-2012. Multivariate regression analysis was performed to compare outcomes of patients with and without re-operation.nnnRESULTSnWe sampled a total of 35 058 patients who underwent kidney transplant. Of these, 770 (2.2%) had re-operation during the same hospitalization. Re-operation was associated with a significant increase in mortality (30.4% vs. 3%; adjusted odds ratio [AOR] 4.62; p<0.01), mean total hospital charges (

The Incidence and Impact of Positive Culture in Deceased Kidney Donors.: 891

249 425 vs.