Sustained in vivo perfusion of a re-endothelialized tissue engineered kidney graft in a human-scale animal model.

Introduction: Despite progress in whole-organ decellularization and recellularization, maintaining long-term perfusion in vivo remains a hurdle to realizing clinical translation of bioengineered kidney grafts. The objectives for the present study were to define a threshold glucose consumption rate (GCR) that could be used to predict in vivo graft hemocompatibility and utilize this threshold to assess the in vivo performance of clinically relevant decellularized porcine kidney grafts recellularized with human umbilical vein endothelial cells (HUVECs). Materials and methods: Twenty-two porcine kidneys were decellularized and 19 were re-endothelialized using HUVECs. Functional revascularization of control decellularized (n = 3) and re-endothelialized porcine kidneys (n = 16) was tested using an ex vivo porcine blood flow model to define an appropriate metabolic glucose consumption rate (GCR) threshold above which would sustain patent blood flow. Re-endothelialized grafts (n = 9) were then transplanted into immunosuppressed pigs with perfusion measured using angiography post-implant and on days 3 and 7 with 3 native kidneys used as controls. Patent recellularized kidney grafts underwent histological analysis following explant. Results: The glucose consumption rate of recellularized kidney grafts reached a peak of 39.9 ± 9.7 mg/h at 21 ± 5 days, at which point the grafts were determined to have sufficient histological vascular coverage with endothelial cells. Based on these results, a minimum glucose consumption rate threshold of 20 mg/h was set. The revascularized kidneys had a mean perfusion percentage of 87.7% ± 10.3%, 80.9% ± 33.1%, and 68.5% ± 38.6% post-reperfusion on Days 0, 3 and 7, respectively. The 3 native kidneys had a mean post-perfusion percentage of 98.4% ± 1.6%. These results were not statistically significant. Conclusion: This study is the first to demonstrate that human-scale bioengineered porcine kidney grafts developed via perfusion decellularization and subsequent re-endothelialization using HUVEC can maintain patency with consistent blood flow for up to 7 days in vivo. These results lay the foundation for future research to produce human-scale recellularized kidney grafts for transplantation.

Outcomes of de novo belatacept-based immunosuppression regimen and avoidance of calcineurin inhibitors in recipients of kidney allografts at higher risk for underutilization.

To describe an experience using a protocol using de novo belatacept (DNB) based maintenance immunosuppression in the setting of lymphocyte depletion. A retrospective, observational study was performed on 37 kidney transplant recipients treated with the DNB protocol, which was defined as belatacept initiated within 7 days after a kidney transplant with steroids and mycophenolate with anti-thymocyte globulin (ATG) induction without concomitant calcineurin inhibitors (CNIs). Patients who received a deceased donor kidney meeting one or more of the following criteria: anticipated cold ischemia time (CIT) greater than 24 h, donation after cardiac death, donor acute kidney injury, and a Kidney Donor Profile Index (KDPI) >85% during the study period were included. Patient survival at 1 year was 97.3% and graft survival was 94.6%. Delayed graft function (DGF) occurred in 40.54% of the patients. Two patients experienced a Banff 1B acute cellular rejection. BK viremia was detected in 32.4% of patients. The mean estimated glomerular filtration rate (eGFR) calculated with the use of modification of diet in renal disease (MDRD) equation at 1 year in the study group was 54.7 ml/min/1.73 m2 . We believe that utilization of the DNB protocol, which allows early CNI avoidance, may decrease organ discard rates.

Different outcomes after kidney transplantation between African Americans and Whites: A matter of income? A single-center study.

BACKGROUND: Our center has one of the largest representations of African Americans in listed and transplanted patients. We investigated if and how racial differences affect outcomes in our patient population. METHODS: We performed a retrospective analysis of all kidney transplants in African American and (non-Hispanic) White patients in our center from 1/1/2005 to 12/31/2014. Cox regression was performed to evaluate the adjusted hazard ratios for graft loss. We investigated the influence of socioeconomic status on transplant outcomes. We stratified our patients into three groups based on income: lower (<$50 000 annual household income), medium ($50 000-100 000 annual household income), and higher (>$100 000 annual household income. RESULTS: There were 1333 patients in our study, 696 Whites and 637 African Americans. The 1-, 5-, and 10-year graft survival between the two groups was 96.5% vs 91.1%, 89% vs 80.7%, and 77% vs 66.3%, respectively (P < .001 by Log Rank, Breslow and Taron-Ware). When we compared the two groups separately in each income category, we found no statistical difference between African Americans and Whites in graft survival. In the regression model, income and not race was the significant factor influencing graft survival (P < .001 vs P = .61).

Reconstruction of a Pancreatic Allograft With Variant Arterial Anatomy for Transplantation.

Donor pancreas utilization rates remain low and aberrant donor anatomy can lead to organ discard by transplant centers. We report on a case of successful pancreas transplantation using a graft with variant arterial anatomy demonstrating that arterial reconstruction is a viable option if aberrant anatomy is encountered at the donor operation. Efforts must be made to use all pancreas grafts that are felt to be of appropriate quality.

The impact of donor liver allograft fibrosis on patients undergoing liver transplantation.

BACKGROUND: The utilization of extended criteria liver allografts (ECD) shortens time to transplantation. OBJECTIVE: To characterize the effect of liver allograft fibrosis on graft and patient survival after liver transplantation (LT), with particular attention to fibrosis progression. METHODS: Retrospective database search of donor and recipient liver allograft histology of liver transplants performed between 2007 and 2011. Donor and patient characteristics were analyzed. RESULTS: One hundred and one patients underwent LT with donor liver allografts with early-stage fibrosis (stage 1 fibrosis and stage 2 fibrosis). The level of liver fibrosis did not progress in 40% of the patients tested, and there was a regression of fibrosis in 30%. At a median follow-up of 71 months, of 101 patients transplanted with fibrotic livers, 63 patients (63%) were alive with functioning initial grafts, six patients (6%) were retransplanted, and 35 patients expired. The graft survival rates were 82% and 69% at 1 and 5 years, respectively. Graft survival differences were not found to be statistically significant between the degrees of liver allograft fibrosis: 5-year graft survival (73% for stage 1 fibrosis and 62% for stage 2 fibrosis, P = .24). The entire fibrosis group was further compared with a control group of 208 consecutive primary liver transplant patients with allografts having no fibrosis. The 5-year graft survival was not significantly different between the groups (69% for the fibrosis group vs 75% for the nonfibrosis group, P = .19). Survival was also not statistically different between the groups (5-year survival of 73% for the fibrosis group vs 79% for the nonfibrosis group, P = .2). In patients with HCV, graft survival differences were not found to be statistically significant with the use of early-stage fibrotic livers: 5-year graft survival of 60% for fibrosis group vs 70% for the nonfibrosis group, P = .22). CONCLUSION: This study demonstrates that allografts with early-stage fibrosis achieve acceptable long-term survival after liver transplantation. Given these preliminary results, the use of organs with early-stage fibrosis warrants further studies at a larger scale to validate these results.

Early conversion to belatacept after renal transplantation.

Belatacept is a non-nephrotoxic immunosuppressive agent, which may make it the ideal agent for patients with delayed or slow graft function on calcineurin inhibitors. There are limited data on conversion of patients to belatacept within 6 months of transplantation. Between January 2012 and December 2015, 16 patients were converted to belatacept for delayed or poor graft function (eGFR<30 mL/min/1.73 m2 , MDRD); three were HIV positive. Conversion protocols were analyzed in patients ≤4 months and 4-6 months post-transplantation. Mean serum creatinine levels after belatacept conversion were compared with preconversion levels. Patient survival was 100%, and graft survival was 88%. The mean creatinine fell from 3.9±1.82 mg/dL prebelatacept conversion to 2.1±1.1 mg/dL at 6 months and 1.9±0.47 mg/dL (median 1.8 mg/dL) at 12 months postconversion. There was no significant increased risk of rejection, infection, or malignancy. HIV parameters remained largely stable. Early conversion to belatacept in patients with DGF or slow graft function is safe and efficacious, in a single-center nonrandomized retrospective analysis.

Upper midline incision for living donor right hepatectomy.

BACKGROUND: Living donor liver transplantation is a viable option to increase access to transplantation and techniques to limit the operative incision is one way to increase donation by decreasing donor morbidity. We describe our experience with a limited upper midline incision (UMI) for living donor right hepatectomy. STUDY DESIGN: Prospective data were collected on 58 consecutive living liver donors who underwent right hepatectomy via a UMI. RESULTS: Donor median age was 32 years, with median body mass index of 24.6. The mean incision length was 11.7 cm. Ten liver grafts included middle hepatic vein. The mean graft volume by preoperative imaging was 940 cc. The mean operative time was 407 minutes; cellsaver was utilized in 35 patients with median of 1 unit. Mean peak aspartate transaminase (AST) and alanine transaminase (ALT) were 492 and 469, and peak bilirubin and international normalized ratio (INR) were 3.3 and 1.8. The average length of stay was 6 days. There were 10 Clavien grade I and 11 Clavien grade II complications. Three patients developed an incisional hernia requiring surgical repair. CONCLUSION: Living liver donor hepatectomy can be safely performed through a UMI. This approach consolidates the steps of liver mobilization, hilar dissection, and parenchymal transection in a single-exposure technique, with incision comparable to the laparoscopic-assisted modality.

Novel and Conservative Approaches Towards Effective Management of Plantar Fasciitis.

We assessed the effectiveness of the different treatments for plantar fasciitis (PF) based on the changes in functional outcomes. A systematic literature search was carried out and studies from 2010 to 2016 were included in this review. The databases from Google Scholar, PubMed and Cochrane were used for the various treatment modalities of plantar fasciitis. The objectives measured included visual analog scale (VAS), Roles and Maudsley scale, foot function index (FFI), plantar fascia thickness and American Orthopedic Foot and Ankle Society (AOFAS) ankle-hind foot scale as the tools to predict the improvement in symptoms of pain and discomfort. Eight randomized controlled trails that met the selection criteria were included in this review. Extracorporeal shock wave lithotripsy (ESWL) with botulinum toxin type A, corticosteroid injections, autologous whole blood and plasma treatment, novel treatments like cryopreserved human amniotic membrane, effect of placebo, platelet rich plasma injections and corticosteroid injections, physiotherapy and high strength training were analyzed. All the treatment modalities applied did lead to the reduction in pain scores, but for long term management autologous condition plasma and platelet rich plasma are the preferred treatment options. Impact of physiotherapy and high strength training is equivalent to corticosteroid injections and hence is suited for patients avoiding invasive forms of treatment.

Hepatitis C and Human Immunodeficiency Virus Kidney Transplantation: The Mount Sinai Experience.

Mount Sinai Hospital in New York has a long history in the field of organ transplantation. The first kidney transplant at Mount Sinai was performed in 1967 by the late Dr. Lewis Burrows and the first laparoscopic donor nephrectomy in New York was performed at Mount Sinai in 1996. Over 3000 kidney transplantations have been performed at Mount Sinai. In the early 1990s, the first hepatitis C virus (HCV) positive patient at Mount Sinai underwent a kidney transplant and the first kidney transplant in a patient with human immunodeficiency virus (HIV) in New York was performed at Mount Sinai in 2001. In general, these patients have done well after renal transplantation, with outcomes similar to those seen in non-infected patients. This chapter will describe the evolution of immunosuppressive regimens in HCV positive and HIV positive patients, and will describe the outcomes of kidney transplantation in these patients. Given the favorable outcomes, it is reasonable to continue to offer renal transplantation as a treatment for end stage renal disease patients with HCV and/or HIV.