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How to improve the long-term prognosis of transplant kidney and solve the shortage of donor kidney are still two major problems that plague clinicians. Among them, ischemia-reperfusion injury (IRI), rejection, infection, and immunosuppressive therapy are important issues in the research field of renal transplantation. Therefore, strengthening the literature study in the field of renal transplantation and understanding the nature of transplant kidney related diseases and international frontier research hotspots, help to further improve the function and prolong the survival time of the transplant kidney in clinic. This article interpreted literatures on the research hotspots and new progress in the field of renal transplantation in the third quarter of 2020, combined with the meeting minutes of the 12th Lingnan Reading Club, and reviewed from the three aspects of IRI, rejection and infection.

Objective To explore the variation trend of natural killer (NK) cell subsets in the recipients infected with cytomegalovirus (CMV) after renal transplantation. Methods Clinical data of 92 renal transplant recipients were retrospectively analyzed. All recipients were divided into the CMV infection group (n=43), CMV infection recovery group (n=13), stable renal function group (n=15), rejection group (n=11) and other infection group (n=10). In addition, healthy adult volunteers were enrolled in the healthy control group (n=15). The proportion of NK cells in peripheral blood, the expression proportion and the mean fluorescence intensity (MFI) of CD226 and CD16 in NK cells were observed and statistically compared among different groups. Results The proportion of NK cells was 4.9% (2.2%, 11.5%) in the CMV infection group and 3.7% (2.3%, 6.5%) in the CMV infection recovery group, which were significantly lower than those in the other groups (all P < 0.05). The expression proportion of CD226 and CD16 in NK cells in the CMV infection group was significantly lower compared with those in the healthy control group and stable renal function group(all P < 0.05). The expression proportion of CD226 and CD16 in NK cells in the CMV infection recovery group was remarkably higher than those in the CMV infection group (both P < 0.05). The MFI of CD226 and CD16 in the CMV infection group was significantly lower than those in the healthy control group (both P < 0.05). The MFI of CD226 and CD16 in the CMV infection recovery group was significantly higher than those in the CMV infection group (both P < 0.05). Conclusions The expression proportion and MFI of CD226 and CD16 in NK cells are down-regulated in CMV infection period, whereas up-regulated during the CMV infection recovery period, prompting that CD226 and CD16 expressed by NK cells are intimately correlated with the course of CMV infection.

Objective To investigate the application value of Multi-Latex polygranular technique joint detection of kidney injury-related urinary microproteins in noninvasive diagnosis after renal transplantation. Methods Clinical data of 72 recipients undergoing renal transplantation were retrospectively analyzed. According to the level of serum creatinine (Scr), the recipients were divided into normal renal function group (group A, n=14), mild kidney injury (group B, n=37), and severe kidney injury group (group C, n=21). 20 healthy volunteers were selected as the healthy control group (HC group). The contents of urinary retinol binding protein (RBP), microalbumin (mAlb), IgG, transferrin (TRF), α1-microglobulin (MG), and β2-MG of subjects in each group were detected using the Multi-Latex polygranular technique. The correlation between urinary microproteins and Scr, blood urea nitrogen (BUN) was analyzed. The differences of urinary microproteins in each group were compared. And the diagnostic value of single and joint detection of urinary microproteins was evaluated. Results Six kinds of urinary microproteins in HC group and group A were significantly lower than those in group B and group C, and six kinds of urinary microproteins in group B were significantly lower than those in group C (all P < 0.01). Six kinds of urinary microproteins in renal transplant recipients were positively correlated with BUN. RBP, mAlb, α1-MG, and β2-MG were positively correlated with Scr. The correlations were statistically significant (P < 0.001-0.05). The diagnostic value of joint detection of urinary microproteins is better than the detection of single index, among which TRF+mAlb+RBP+α1-MG quadruple detection had the highest diagnostic value. Conclusions Six kinds of urinary microproteins can be used as specific indicators to reflect graft renal function. The polygranular technique can simultaneously detect its contents and achieve noninvasive diagnosis. The diagnosis based on TRF+mAlb+RBP+α1-MG quadruple detection is expected to further improve the noninvasive diagnosis system after renal transplantation.

Xenotransplantation is the most promising method to resolve the organ shortage problem in the future. In recent years, the advances in gene editing and immunological technique have driven the rapid development of xenotransplantation. However, there are still many insurmountable obstacles in the clinical application of xenotransplantation, among which the rejection is the most important cause of the xenotransplantation failure. Regulatory immunological cells are a group of immunological cells with the negative regulation function in the body, which can inhibit allotransplantation rejection and prolong the survival time of the graft. This paper summarized the research progress of regulatory immunological cells in the xenotransplantation application in recent years, providing reference for the prevention and treatment of xenotransplantation rejection.

In the second half of 2019, the last four sessions of Transplant Cloud College jointly established by Chinese Research Hospital Association and Medical Neighbor Network were successfully held. During the courses in the second half of this year, the lecturers from each institution mainly focused upon four topics including management of hyperuricemia (HUA) after kidney transplantation, renal graft pathology, diagnosis and treatment of acute antibody-mediated rejection (AMR) after kidney transplantation and pulmonary infection after liver transplantation. All participants delivered discussions and exchanges in kidney and liver transplantation from multiple perspectives.

Rejection is the main cause of transplantation failure. Currently, the specificity and sensitivity of clinical parameters are relatively poor, which cannot accurately prompt the exact cause of rejection. It is of great clinical significance to explore novel biomarkers for monitoring the rejection. In this article, the latest research progress on the biomarkers of rejection risk in organ transplantation were summarized from the perspectives of transplantation pathology, immune cells and regulatory immune cells, non-human leukocyte antigen antibodies, exosomes, cell-free DNA and combination gene prediction, aiming to provide reference for early warning and treatment of rejection in organ transplantation.

In December 2019, a number of cases of pneumonia with unknown causes were successively reported in multiple hospitals in Wuhan City, Hubei Province, China. The pathogen is a novel coronavirus, which can lead to novel coronavirus pneumonia (COVID-19) and even threaten the patients' lives. In the following, the COVID-19 epidemic is spreading rapidly in many provinces and cities. It is particularly important to summarize and analyze the clinical characteristics of COVID-19 in solid organ transplantation (SOT) recipients and to optimize the prevention, early diagnosis and treatment strategies. Therefore, we organized Chinese experts in the field of organ transplantation to draft this article according to the characteristics of lung infection of SOT recipients and the characteristics of current COVID-19 by referring to relevant guidelines and specifications at home and abroad, aiming to provide reference for transplant physicians in China. This management strategy will be revised at any time with the deepening understanding of the COVID-19 infection.

As proposed in 2019 Annual Congress of the Chinese Society of Organ Transplantation, the overall objective of the development of organ transplantation in China is to deepen the structural reform of the supply side comprehensively, to promote the transition of organ transplantation from the quantitative scale model to the quality-lifting type, and to promote the scientific, balanced, standardized and high-quality development of organ transplantation. This paper introduces the construction of quality management system and the implementation of quality improvement program in the field of surgery and transplantation in the United States, summarizes the preliminary work of how to combine foreign experience to promote the construction of quality improvement program of renal transplantation in our country, and proposes the idea of extending the quality improvement program of organ transplantation.

Objective To summarize the clinical treatment experience of carbapenem-resistant Klebsiella pneumoniae (CRKP) infection after renal transplantation in donation after cardiac death (DCD) era. Methods Clinical data of 10 donors and 17 recipients with CRKP infection after DCD renal transplantation from January 2015 to January 2019 were retrospectively analyzed. Both donors and recipients received bacterial culture and drug sensitivity test. Clinical manifestations, treatment and outcome of CRKP-infected recipients were recorded. Results Seven donors were infected with CRKP. After pretreatment, CRKP in 2 cases turned negative, CRKP in 5 donors did not turn negative. All renal grafts were treated with tigecycline+meropenem+voriconazole lavage to prevent infection. Among 17 recipients with CRKP infection, 11 cases were positive for blood culture, 10 positive for urine culture, 3 positive for sputum culture, 3 positive for incisional secretion and 3 positive for retroperitoneal drainage. Clinical manifestations included fever in 8 cases, rupture and hemorrhage of the transplant renal artery in 7 cases or thrombosis in the transplant renal artery in 1 case, bladder irritation sign in 3 cases and cough with brick red jelly-like sputum in 1 case, respectively. Five patients were treated with tigecycline+meropenem, 1 patient suffered from renal graft loss and 4 recipients died. Twelve patients were treated with ceftazidime-avibactam +meropenem, 3 patients presented with renal graft loss and 1 recipient died. Conclusions CRKP-infected donor is not the absolute contraindication of renal transplantation. Pretreatment of donor infection and early administration of sufficient sensitive antibiotics can cure CRKP infection and improve the clinical prognosis of renal transplant recipients.

Objective To investigate the effect of common immunosuppressants on the follicular regulatory T cells (Tfr cells) and regulatory B cells (Breg cells). Methods Peripheral blood samples were collected from 6 healthy volunteers (5 mL per case).The lymphocytes were isolated by human lymphocyte isolation solution and cultured.The cells were divided into the control group (without supplement of immunosuppressants), ciclosporin group (250 ng/mL), tacrolimus group (10 ng/mL) and sirolimus group (10 ng/mL).The cells were stimulated with corresponding immunosuppressants for 48 h, respectively.The proportion of Breg and Tfr cells in the lymphocytes in each group was detected by flow cytometry.The content of interleukin (IL)-21 in the supernatants of each group was detected by enzyme-linked immunosorbent assay (ELISA). Results Compared with the control group, the proportion of Breg cells in the lymphocytes in the ciclosporin, tacrolimus and sirolimus groups was all significantly increased (all P < 0.05).In the ciclosporin group and tacrolimus group, the proportion of Tfr cells in the lymphocytes was both significantly elevated (both P < 0.05), whereas the proportion of Tfr cells in the lymphocytes in the sirolimus group was significantly decreased (P < 0.05).ELISA demonstrated that compared with the control group, the IL-21 content in the supernatants in the ciclosporin and tacrolimus groups was both significantly decreased (both P < 0.05).Use of sirolimus exerted no significant effect upon the secretion of IL-21 (P > 0.05). Conclusions Ciclosporin and tacrolimus can inhibit the immune response of B cells.

Objective To investigate the inhibitory effect and underlying mechanism of mesenchymal stem cell (MSC) derived from different sources on follicular helper T cell (Tfh cell). Methods Umbilical cord-derived MSC (UC MSC), bone marrow-derived MSC (BM MSC) and fat-derived MSC (Fat MSC) were co-cultured with peripheral blood mononuclear cell (PBMC) for 48 h. A control group was established. Flow cytometry was adopted to calculate the proportion of Tfh cells among the lymphocytes in four groups. The content of interleukin (IL)-21 in the supernatant was detected by enzyme-linked immune absorbent assay (ELISA) in four groups. BM MSC was co-cultured with PBMC, and supplemented with indoleamine 2, 3-dioxygenase (IDO) inhibitor 1-methyl tryptophan (1-MT), IL-10 antibody, human leukocyte antigen (HLA)-G antibody in the 1-MT group, IL-10 inhibition group, HLA-G inhibition group and BM MSC group without addition of other substances. After 48 h culture, flow cytometry was used to detect the percentage of Tfh cells among lymphocytes. Results Flow cytometry demonstrated that compared with the control group, the proportion of Tfh cells in the BM MSC group was significantly decreased (P < 0.05). Compared with the BM MSC group, the percentage of Tfh cells in the UC MSC and Fat MSC groups was significantly higher (both P < 0.05). ELISA revealed that compared with the control group, the IL-21 content in the BM MSC group was significantly decreased (P < 0.05). Compared with the BM MSC group, the IL-21 contents were considerably higher in the UC MSC and Fat MSC groups (both P < 0.05). The analysis of underlying mechanism revealed that the proportions of Tfh cells in the 1-MT, IL-10 inhibition and the HLA-G inhibition groups were (1.75±0.07)%, (1.31±0.09)% and (1.50±0.03)%, respectively, which were significantly higher than (1.03±0.43)% in the BM MSC group (all P < 0.05). Conclusions BM MSC exerts the highest inhibitory effect upon the differentiation of Tfh cell and IL-21. The mechanism underlying suppressing the differentiation of Tfh cells differentiation is probably correlated to promoting the secretion of IDO.

Objective To analyze and summarize the clinical features and diagnosis and treatment experience of brucellosis after renal transplantation. Methods Clinical data of one case with brucellosis after renal transplantation admitted to the 309th Hospital of Chinese People's Liberation Army in October 2016 was collected. The clinical features, diagnosis and treatment were retrospectively analyzed. Clinical experience was summarized and literature review was conducted. Results At 3 months after renal transplantation, the patient suffered from temperature rise without known causes and presented with fever in the morning with a duration of 3 d. The route of infection was unknown, and the symptoms of alternative types of infection were not obvious. Empirical anti-infectious therapy was delivered for 1 week and yielded no efficacy. Blood culture test confirmed the diagnosis of brucella melitensis infection. The treatment included anti-infecting by the rifampicin, doxycycline, sulfamethoxazole, preventing the incidence of complications actively and protecting the liver and renal function. High clinical efficacy was achieved. During the 1-year follow up after discharge, the renal graft was stable and no other infectious symptoms, such as fever was found. Conclusions Brucellosis with unknown route of infection after renal transplantation is extremely rare and the common symptom is Malta fever. When the empirical anti-infectious treatment is not effective, blood culture and other related tests should be performed to confirm the diagnosis. The combination of rifampicin and doxycycline is recommended.

Objective To explore the effect of umbilical cord mesenchymal stem cells with positive human leukocyte antigen (HLA)-G on inducing the production of regulatory T cells (Treg) in vitro. Methods Umbilical cord mesenchymal stem cells were isolated from umbilical cord of neonates. PEGFP-N1-HLA-G plasmid was transfected into the human umbilical cord mesenchymal stem cells by liposome transfection, as PEGFP-N1-HLA-G group. PEGFP-N1 empty vector plasmid was transfected into the human umbilical cord mesenchymal stem cells, as PEGFP-N1 group. The human umbilical cord mesenchymal stem cells without empty vector under the same conditions were set as blank control group. Markers of the umbilical cord mesenchymal stem cells were detected using flow cytometry. The expression of HLA-G protein in each group of cells was identified by Western Blot. After mixed-culturing with CD4+T cells in peripheral blood of healthy subjects for 24 h and 48 h, the proportion of CD4+ CD25+ Foxp3+Treg in total T cells of each group was detected by flow cytometry. Results CD45, CD34 and HLA-DR presented negative expression on umbilical cord mesenchymal stem cells, while CD29, CD44 and CD105 presented positive expression. HLA-G protein could be expressed in the PEGFP-N1-HLA-G group, which had statistically significant difference compared with the blank control group and PEGFP-N1 group (both P < 0.01). After PEGFP-N1-HLA-G group and CD4+T cells were mixed-cultured for 24 h and 48 h, CD4+ CD25+ Foxp3+Treg accounted for (15.3±1.9)% and (14.3±2.1)% of the total T cells respectively, both of which presented statistically significant difference compared with the blank control group and PEGFP-N1 group (all P < 0.05). Conclusions Umbilical cord mesenchymal stem cells with HLA-G gene modified can effectively induce the production of CD4+ CD25+ Foxp3+Treg in vitro.

Objective To analyze the impairment of renal allograft function in renal transplant recipients caused by BK virus infection after renal transplantation. Methods Clinical data of 210 recipients who underwent allogenic renal transplantation and received BK virus monitoring regularly were analyzed retrospectively. The incidence of BK viruria, viremia and BK virus nephropathy (BKVN) after renal transplantation was summarized. The effect of BK virus infection on renal allograft function and prognosis of renal allograft function after the removement of BK virus were analyzed. Results Among the 210 recipients, there were 46 cases with pure viruria, 46 cases with viremia complicated with viruria and 7 cases with BKVN confirmed by pathological biopsy. The level of serum creatinine (Scr) in the recipients with viremia after renal transplantation was linearly related to BK viral load in urine and blood (r=0.594, 0.672, both P < 0.01). The level of Scr increased significantly when BK viral load in blood of the recipients with viremia was found positive for the first time, and increased continuously after viremia sustained. And the level of Scr decreased slightly when blood viral load turned to negative after treatment, but still significantly higher than before virus infection. All the above differences were statistically significant (all P < 0.05). Compared with the basic level, there was no significant difference in the level of Scr of recipients with pure viruria during positive viruria (all P>0.05). Conclusions It will impair the renal allograft function when BK viremia occurs after renal transplantation, and it is necessary to monitor viral infection regularly. Once the blood BK virus is found positive, it shall be implemented immediately to reduce the intensity of immunosuppression as the preferred clinical intervention.