BACKGROUND: Delayed graft function (DGF) is the main cause of renal function failure after kidney transplantation. This study aims at investigating the value of hypothermic machine perfusion (HMP) parameters combined with perfusate biomarkers on predicting DGF and the time of renal function recovery after deceased donor (DD) kidney transplantation. METHODS: HMP parameters, perfusate biomarkers and baseline characteristics of 113 DD kidney transplantations from January 1, 2019 to August 31, 2019 in the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively analyzed using univariate and multivariate logistic regression analysis. RESULTS: In this study, the DGF incidence was 17.7% (20/113); The multivariate logistic regression results showed that terminal resistance (OR: 1.879, 95% CI 1.145-3.56) and glutathione S-transferase (GST)(OR = 1.62, 95% CI 1.23-2.46) were risk factors for DGF; The Cox model analysis indicated that terminal resistance was an independent hazard factor for renal function recovery time (HR = 0.823, 95% CI 0.735-0.981). The model combining terminal resistance and GST (AUC = 0.888, 95% CI: 0.842-0.933) significantly improved the DGF predictability compared with the use of terminal resistance (AUC = 0.756, 95% CI 0.693-0.818) or GST alone (AUC = 0.729, 95% CI 0.591-0.806). CONCLUSION According to the factors analyzed in this study, the combination of HMP parameters and perfusate biomarkers displays a potent DGF predictive value.
Biomarkers ; Delayed Graft Function ; Graft Survival ; Humans ; Kidney/physiology* ; Kidney Transplantation/adverse effects* ; Organ Preservation ; Perfusion ; Retrospective Studies ; Tissue Donors

Background: Hypothermic machine perfusion (HMP) is being used more often in cardiac death kidney transplantation; however, the significance of assessing organ quality and predicting delayed graft function (DGF) by HMP parameters is still controversial. Therefore, we used a readily available HMP variable to design a scoring model that can identify the highest risk of DGF and provide the guidance and advice for organ allocation and DCD kidney assessment. Methods: From September 1, 2012 to August 31, 2016, 366 qualified kidneys were randomly assigned to the development and validation cohorts in a 2:1 distribution. The HMP variables of the development cohort served as candidate univariate predictors for DGF. The independent predictors of DGF were identified by multivariate logistic regression analysis with a P < 0.05. According to the odds ratios (ORs) value, each HMP variable was assigned a weighted integer, and the sum of the integers indicated the total risk score for each kidney. The validation cohort was used to verify the accuracy and reliability of the scoring model. Results: HMP duration (OR = 1.165, 95% confidence interval [CI]: 1.008-1.360, P = 0.043), resistance (OR = 2.190, 95% CI: 1.032-10.20, P < 0.001), and flow rate (OR = 0.931, 95% CI: 0.894-0.967, P = 0.011) were the independent predictors of identified DGF. The HMP predictive score ranged from 0 to 14, and there was a clear increase in the incidence of DGF, from the low predictive score group to the very high predictive score group. We formed four increasingly serious risk categories (scores 0-3, 4-7, 8-11, and 12-14) according to the frequency associated with the different risk scores of DGF. The HMP predictive score indicates good discriminative power with a c-statistic of 0.706 in the validation cohort, and it had significantly better prediction value for DGF compared to both terminal flow (P = 0.012) and resistance (P = 0.006). Conclusion The HMP predictive score is a good noninvasive tool for assessing the quality of DCD kidneys, and it is potentially useful for physicians in making optimal decisions about the organs donated.
Adult ; Delayed Graft Function ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Kidney Transplantation ; adverse effects ; methods ; Logistic Models ; Male ; Multivariate Analysis ; Odds Ratio ; Organ Preservation

The quality of a donor liver after cardiac death is closely associated with energy metabolism during preservation. Ex vivo mechanical perfusion has broad application prospects because this technique can help energy metabolism and repair ischemia injury of donors' livers. Some core issues are presented in this review in order to provide references for propelling secure application of liver transplantation based on donation after cardiac death.
Death ; Humans ; Liver ; Liver Transplantation ; Organ Preservation ; methods ; Perfusion ; methods ; Warm Ischemia ; adverse effects

Despite strict pre- and post-transplantation screening, the incidence of new-onset diabetes after transplantation (NODAT) remains as high as 60%. This complication affects the risk of cardiovascular events and patient and graft survival rates. Thus, reducing the impact of NODAT could improve overall transplant success. The pathogenesis of NODAT is multifactorial, and both modifiable and nonmodifiable risk factors have been implicated. Monitoring and controlling the blood glucose profile, implementing multidisciplinary care, performing lifestyle modifications, using a modified immunosuppressive regimen, administering anti-metabolite agents, and taking a conventional antidiabetic approach may diminish the incidence of NODAT. In addition to these preventive strategies, inhibition of dipeptidyl peptidase-4 (DPP4) by the gliptin family of drugs has recently gained considerable interest as therapy for type 2 diabetes mellitus and NODAT. This review focuses on the role of DPP4 inhibitors and discusses recent literature regarding management of NODAT.
Animals ; Blood Glucose/drug effects/metabolism ; Diabetes Mellitus/diagnosis/*drug therapy/enzymology/etiology ; Dipeptidyl Peptidase 4/*metabolism ; Dipeptidyl-Peptidase IV Inhibitors/*therapeutic use ; Humans ; Organ Transplantation/*adverse effects ; Risk Assessment ; Risk Factors ; Treatment Outcome

Epstein Barr virus (EBV)-associated lymphoproliferative diseases (LPDs) express all EBV latent antigens (type III latency) in immunodeficient patients and limited antigens (type I and II latencies) in immunocompetent patients. Post-transplantation lymphoproliferative disease (PTLD) is the prototype exhibiting type III EBV latency. Although EBV antigens are highly immunogenic, PTLD cell proliferation remains unchecked because of the underlying immunosuppression. The restoration of anti-EBV immunity by EBV-specific T cells of either autologous or allogeneic origin has been shown to be safe and effective in PTLDs. Cellular therapy can be improved by establishing a bank of human leukocyte antigen-characterized allogeneic EBV-specific T cells. In EBV+ LPDs exhibiting type I and II latencies, the use of EBV-specific T cells is more limited, although the safety and efficacy of this therapy have also been demonstrated. The therapeutic role of EBV-specific T cells in EBV+ LPDs needs to be critically reappraised with the advent of monoclonal antibodies and other targeted therapy. Another strategy involves the use of epigenetic approaches to induce EBV to undergo lytic proliferation when expression of the viral thymidine kinase renders host tumor cells susceptible to the cytotoxic effects of ganciclovir. Finally, the prophylactic use of antiviral drugs to prevent EBV reactivation may decrease the occurrence of EBV+ LPDs.
Antiviral Agents/therapeutic use ; Cell- and Tissue-Based Therapy ; DNA Methylation ; Epstein-Barr Virus Infections/*complications ; Genome, Viral ; Hematopoietic Stem Cell Transplantation ; Herpesvirus 4, Human/*physiology ; Humans ; Immunotherapy, Adoptive ; Lymphoproliferative Disorders/diagnosis/*etiology/*therapy ; Organ Transplantation/adverse effects ; T-Lymphocytes/immunology ; Transplantation, Homologous ; Virus Latency

OBJECTIVETacrolimus (FK506) is an immunosuppressive drug, which is widely used to prevent rejection of transplanted organs. However, chronic administration of FK506 leads to hypertension in solid organ transplantation patients, and its molecular mechanisms are much more complicated. In this review, we will discuss the above-mentioned molecular mechanisms of FK506-induced hypertension in solid organ transplantation subjects.

DATA SOURCESThe data analyzed in this review were mainly from relevant articles without restriction on the publication date reported in PubMed. The terms "FK506" or "tacrolimus" and "hypertension" were used for the literature search.

STUDY SELECTIONOriginal articles with no limitation of research design and critical reviews containing data relevant to FK506-induced hypertension and its molecular mechanisms were retrieved, reviewed and analyzed.

RESULTSThere are several molecular mechanisms attributed to FK506-induced hypertension in solid organ transplantation subjects. First, FK506 binds FK506 binding protein 12 and its related isoform 12.6 (FKBP12/12.6) and removes them from intracellular ryanodine receptors that induce a calcium ion leakage from the endoplasmic/sarcoplasmic reticulum. The conventional protein kinase C beta II (cPKCβII)-mediated phosphorylation of endothelial nitric oxide (NO) synthase at Thr495, which reduces the production of NO, was activated by calcium ion leakage. Second, transforming growth factor receptor/SMAD2/3 signaling activation plays an important role in Treg/Th17 cell imbalance in T cells which toget converge to cause inflammation, endothelial dysfunction, and hypertension following tacrolimus treatment. Third, the activation of with-no-K(Lys) kinases/STE20/SPS1-related proline/alanine-rich kinase/thiazide-sensitive sodium chloride co-transporter (WNKs/SPAK/NCC) pathway has a central role in tacrolimus-induced hypertension. Finally, the enhanced activity of renal renin-angiotensin-aldosterone system seems to play a crucial role in the pathophysiology of FK506-induced hypertension.

CONCLUSIONFK506 plays a predominant role in the pathophysiology of hypertension in solid organ transplantation subjects.

Humans ; Hypertension ; chemically induced ; Immunosuppressive Agents ; adverse effects ; therapeutic use ; Organ Transplantation ; adverse effects ; Tacrolimus ; adverse effects ; therapeutic use

OBJECTIVETo investigate the risk factors associated with persistent thrombocytopenia after liver transplantation (LT), and to explore effective measures for prevention.

METHODSOne hundred and twenty-eight adult patients, who received liver transplantation in our hospital between January 2009 and June 2012 and met the inclusive criteria, were enrolled in the study. The clinical data were retrospectively analyzed, including pre-LT spleen volume, main portal vein size, coronary vein size, platelet and white blood cell levels, total bilirubin level and model of end stage liver disease score. The risk factors associated with persistent thrombocytopenia after LT were evaluated by logistic regression analysis. The effect of simultaneous splenic artery coarctation for high risk patients was evaluated with χ2 test.

RESULTSLogistic regression analysis showed that per-LT spleen volume larger than 500 ml (P = 0.012, OR=2.789, 95%CI: 1.249-6.227) and portal vein size beyond 15 mm (P = 0.017, OR = 3.124, 95%CI: 1.230-7.933) were independent risk factors for persistent thrombocytopenia after LT. The incidence rate of persistent thrombocytopenia after LT in patients with or without simultaneous splenic artery coarctation were 16.7% (1/6) and 66.7% (32/48), respectively(P < 0.05).

CONCLUSIONSpleen volume larger than 500 ml and portal vein size beyond 15 mm are risk factors for persistent thrombocytopenia after LT. Simultaneous splenic artery coarctation may reduce the occurrence of persistent thrombocytopenia after LT.

Adult ; Humans ; Liver Transplantation ; adverse effects ; Organ Size ; Portal Vein ; anatomy & histology ; Retrospective Studies ; Risk Factors ; Spleen ; anatomy & histology ; Thrombocytopenia ; epidemiology

No abstract available.
Animals ; Antigen-Presenting Cells/immunology ; Graft Rejection/immunology/*prevention & control ; Graft Survival ; *Histocompatibility ; Humans ; Immunosuppression/*methods ; Intercellular Adhesion Molecule-1/immunology ; Isoantigens/*immunology ; Organ Transplantation/*adverse effects ; *Transplantation Tolerance

OBJECTIVETo evaluate the effects of different CO(2) pneumoperitoneum conditions on renal function in rats and provide experimental evidence for improving renal graft function after transplantation.

METHODSSD rats were randomized into 10 groups (n=12) and subject to CO(2) pneumoperitoneum at different pressures (0.67, 1.33 and 2.0 kPa) for 60 or 120 min. Serum urea nitrogen (BUN), creatinine (Cr) and N-acetyl-β-D-glocosaminidase (NAG) levels were detected after pneumoperitoneum.

RESULTSAs the pressure and time of pneumoperitoneum increased, the renal function deteriorated gradually, showing significant differences between the groups (P<0.05).

CONCLUSIONIncreased pressure and prolonged duration of CO(2) pneumoperitoneum causes impairment of the renal function, suggesting the necessity of reducing the operative time and lowering the pressure of pneumoperitoneum when harvesting renal graft in living donors.

Animals ; Carbon Dioxide ; Female ; Kidney ; physiology ; Kidney Transplantation ; Laparoscopy ; methods ; Male ; Nephrectomy ; methods ; Pneumoperitoneum, Artificial ; adverse effects ; methods ; Rats ; Rats, Sprague-Dawley ; Retroperitoneal Space ; surgery ; Time Factors ; Tissue and Organ Harvesting ; methods

With our rapidly ageing population and advancing treatments for patients with haematological, oncologic and rheumatological diseases, there are increasing numbers of immunocompromised patients presenting to primary care and general hospitals with opportunistic infections. This review considers the trends of these infections across four representative subgroups: fungal infections following haematopoietic stem cell transplant; viral infections post solid organ transplant; mycobacterial infections during treatment with targeted biological agents; and bacterial infections as a cause of fever in neutropenia. We also consider the impact of host, pathogens, environments and treatments on the epidemiology and outcomes of these infections.
Adult ; Bacterial Infections ; complications ; Communicable Diseases ; etiology ; Female ; Fever ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Immunocompromised Host ; Immunosuppressive Agents ; adverse effects ; Male ; Middle Aged ; Mycoses ; etiology ; Neutropenia ; etiology ; Opportunistic Infections ; epidemiology ; etiology ; Organ Transplantation ; adverse effects ; Virus Diseases ; etiology