Human PD-L1 overexpression decreases xenogeneic human T-cell immune responses towards porcine kidneys.

Xenotransplantation offers a promising alternative to circumvent the lack of donated human organs available for transplantation. Different attempts to improve the survival of xenografts led to the generation of transgenic pigs expressing various combinations of human protective genes or knocked out for specific antigens. Currently, testing the efficiency of porcine organs carrying different genetic modifications in preventing xenogeneic immune responses completely relies on in vitro assays, humanized mouse models, or non-human primate transplantation models. However, these tests are often associated with major concerns due to reproducibility and generation of insufficient data as well as they raise ethical, logistical, and economic issues. In this study, we investigated the feasibility of specifically assessing the strength of human T-cell responses towards the kidneys of wild-type (WT) or transgenic pigs overexpressing human programmed death-1 ligand 1 (hPD-L1) during ex vivo kidney perfusion (EVKP). Human T cells were shown to adhere to the endothelium and transmigrate into WT and hPD-L1 kidneys. However, transcript levels of TNF-a and IFN-y as well as cytotoxic molecules such as granzyme B and perforin secreted by human T cells were significantly decreased in the tissue of hPD-L1 kidneys in comparison to WT kidneys. These results were confirmed via in vitro assays using renal endothelial cells (ECs) isolated from WT and hPD-L1 transgenic pigs. Both CD4+ and CD8+ T cells showed significantly lower proliferation rates after exposure to hPD-L1 porcine renal ECs in comparison to WT ECs. In addition, the secretion of pro-inflammatory cytokines was significantly reduced in cultures using hPD-L1 ECs in comparison to WT ECs. Remarkably, hPD-L1 EC survival was significantly increased in cytotoxic assays. This study demonstrates the feasibility of evaluating the human response of specific immune subsets such as human T cells towards the whole xenograft during EVKP. This may represent a robust strategy to assess the potency of different genetic modifications to prevent xenogeneic immune responses and thereby predict the risk of immune rejection of new genetically engineered xenografts.

Predictive value of neutrophil-to-lymphocyte ratio in terms of need for intensive care unit and mortality in maintenance hemodialysis patients with COVID-19.

INTRODUCTION: The transmission risk of Severe Acute Respiratory Syndrome Coronavirus-2 virus infection is increased in maintenance hemodialysis (MHD) patients, and also the disease causes much higher mortality than the normal population. The aim of this study is to define the predictive value of neutrophil-to-lymphocyte ratio (NLR) in terms of worse outcomes in MHD patients. METHODS: A total of 123 MHD patients who had received inpatient care due to COVID-19 infection were included in this multicentered retrospective study. Receiver operating curve analysis were plotted to illustrate C reactive protein (C-rp), systemic inflammatory index (SII) and NLR best cut-off values for estimation of need for intensive care unit (ICU) and mortality. Multivariate regression analysis and Cox proportional hazard models were constructed to determine the association between C-rp, SII and NLR and mortality. RESULTS: Twenty-eight (23%) patients with MHD were dead due to COVID-19. Nonsurvivor patients was significantly older than the survivors (p < 0.001) and also had higher rates of diabetes mellitus (p = 0.01) and coronary artery disease (p = 0.02). Cox regression analysis revealed that NLR >5.17 significantly associated with mortality [HR: 6.508, p < 0.001]. Similarly, SII > 726 [HR: 3.124, p = 0.006] and C-rp > 88 [HR: 4.590, p = 0.002] were significantly associated with mortality due to COVID-19 in hospitalized MHD patients. Multivarite logistic regression analysis showed that age older than 60 years, higher ferritin, and NLR > 5.17 were independent factors associated with mortality. CONCLUSION: NLR had favorable predictive value than the C-rp and SII in terms of need for ICU and mortality in MHD patients. Determining the poor prognosis with simple and easily applicable markers may reduce mortality in these patients with early supportive treatments.

Long-Term Outcomes of Left versus Right Laparoscopic Living Donor Nephrectomy with Multiple Renal Arteries.

OBJECTIVES: The objective of this study was to compare the long-term graft outcomes of left-versus-right donor nephrectomy with multiple renal arteries (MRAs), and therefore creating a reference for the expansion of the potential living kidney donor pool. METHODS: Laparoscopic live donor nephrectomy cases between May 2010 and October 2020 were included in this retrospective cross-sectional study. The data relating to donor and recipient demographics, surgical and anatomical characteristics, recipient, and graft status were retrieved and compared using nonparametric statistical methods and multivariate regression. Analyses were fit for survival factors. RESULTS: A total of 1,009 recipients were included in this retrospective cross-sectional study with their donors. 16.7% of the donors had been discovered to have more than one renal artery supplying the donated kidney. The acute rejection rate was 12.8%. Death-censored graft survival at postoperative year 5 for single renal artery (SRA) transplants was 89.6%, 89.5% for left-sided MRAs, and 88.2% for right-sided ones. CONCLUSIONS: Both right donor nephrectomy and left donor nephrectomy are safe procedures with no significant negatively impacted rates for neither survival nor complications of the recipients in the long-term, compared to SRA ones.

Comparison of Long-Term Outcomes of Standard and Transvaginal Kidney Extraction in Laparoscopic Living Donor Nephrectomy.

Background: A limited number of publications are available in the literature regarding laparoscopic living donor nephrectomy with vaginal extraction (LLDN-VE) for kidney transplantation. The aim of this study was to compare long-term recipient outcomes of standard laparoscopic living donor nephrectomy (S-LLDN) and LLDN-VE. Methods: A total of 652 patients [119 LLDN-VE (18.3%) and 533 S-LLDN (81.7%)] were included in this retrospective cross-sectional study. The data related to donor and recipient demographics, surgical and anatomical characteristics, and recipient and graft status were retrieved and compared using nonparametric statistical methods. Kaplan-Meier and Cox proportional hazards regression analyses were applied to compute survival according to the surgical technique. Results: The mean follow-up duration was 73.0 ± 25.4 months for S-LLDN and 69.8 ± 20.4 months for LLDN-VE recipients. The main determinants of long-term outcomes were the serum creatinine (SCr) levels, death-censored graft survival, and recipient survival at the end of the post-op 5th year. LLDN-VE recipients' discharge SCr was found to be statistically lower (P = .049) than S-LLDN patients. Graft survival rates censored for death were 93.8% for the S-LLDN and 93.3% for the LLDN-VE recipients. Cox regression analysis showed significance for younger donor age (P = .010) with the application of 17 parameters, indicating better graft survival outcomes for kidney recipients with younger donors. Conclusions: Compared with the standard method, the long-term results of LLDN-VE are in accordance with or could even be more advantageous than S-LLDN in certain aspects. LLDN-VE appears to be a feasible, safe, and cosmetically superior approach with no negative postoperative sexual or morbid effects on the donor.

Endoscopic ultrasound-guided liver biopsy using a 20-gauge fine needle biopsy needle with the wet-heparinized suction technique.

OBJECTIVES: The primary aim of this study was to evaluate the histological adequacy of the liver tissue specimens obtained with a 20-gauge fine-needle biopsy needle and the secondary aim was to test the safety endoscopic ultrasound-guided liver biopsy with a 20-gauge fine-needle biopsy needle with the wet-heparinized suction technique. METHODS: Forty patients who underwent endoscopic ultrasound-guided liver biopsy were included in the study. A 20-gauge fine-needle biopsy needle was used with the wet-heparinized suction technique to make one pass each from the left and the right lobe. Histologic characteristics of the specimens were evaluated, and patients were observed after the procedure in order to intervene in case of an adverse event. RESULTS: The median longest core fragment was 22 mm from the left lobe [first quartile-third quartile 20-25 mm, interquartile range (IQR) 5 mm], and 20 mm (first quartile-third quartile 17-22 mm, IQR 5 mm) from the right lobe. The median cumulative core length per patient was 103 mm (91-108 mm, IQR 17 mm). The median cumulative number of complete portal triads per patient was 69.50 (52.25-82.25, IQR 30). The rate of diagnostic yield was 100%. Post-biopsy self-limiting abdominal pain was reported in two patients (5%). The most common histologic diagnosis was fatty liver disease (25%). CONCLUSION: Endoscopic ultrasound-guided liver biopsy with the wet-heparinized suction technique using a 20-gauge fine-needle biopsy needle is a safe alternative method in clinical practice.