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 compare the effects of cyclosporine A (CsA) and tacrolimus (FK506) on BK virus infection after renal transplantation by retrospective clinical study.Methods The data of calcineurin inhibitor (CNI)-based immunosuppression and virus infection were collected in allograft renal transplantation recipients (n =135) from Jan.2014 to Dec.2015.According to the severity of the virus infection the recipients were divided into three groups:viruria,viremia and virus nephropathy.The difference in BK virus infection between FK506 and CsA was compared.Results A total of 135 cases of transplant recipients,postoperative were enrolled.The number of viruria recipients given FK506 and CsA was 41 cases (69.5％) and 18 cases (30.5％),and that of viremia recipients was 26 cases (86.7 ％) and 4 cases (13.3 ％).Statistical analysis showed that CNI immunosuppressive agents had a significant correlation with viremia only (P＜0.05).There was a positive correlation between FK506 and viremia (r =0.423,P =0.018),and CsA showed a negative correlation yet (r =-0.336,P =0.022).Conclusion Tacrolimus is independent risk factors for early BK viremia after kidney transplantation,and CsA may inhibit the progression of BK viremia.

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.

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 309thHospital 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 investigate the relationship between the metabolic rate of tacrolimus (FK506) and BK virus infection early after renal transplantation. Methods Eighty recipients undergoing allogenic renal transplantation in Institute of Organ Transplantation of the 309thHospital of Chinese People's Liberation Army were recruited in this study. The polymorphism of cytochrome P450 (CYP) 3A5 gene was detected in 80 recipients. All patients were divided into fast metabolism group ( CYP3A5*1/*3 and CYP3A5*1/*1 genotypes, n=38) and slow metabolism group ( CYP3A5*3/*3 genotype, n=42) based on the gene detection results. The distribution of CYP3A5 genotypes in 80 recipients was analyzed. The metabolic rate [concentration/dose ratio (C/D value)] of FK506 was statistically compared between two groups. The incidence of BK virus infection events [BK viruria, BK viremia and BK virus nephropathy(BKVN)] within postoperative 6 months were compared between two groups. Results Among 80 recipients, 5 cases (6%) were detected with CYP3A5*1/*1 genotype, 33 (41%) with CYP3A5*1/*3 genotype, and 42 (53%) with CYP3A5*3/*3 genotype. Among the 160 alleles in 80 recipients, 117 CYP3A5*3 allele were identified, suggesting that the mutation rate of CYP3A5*3 allele was 73.1%. In the fast metabolism group, the C/D values at postoperative 1, 3, and 6 months were significantly lower than those in the slow metabolism group (all P<0.01). The incidence rates of BK viruria in the fast and slow metabolism groups were 37% and 29%, 18% and 2% for BK viremia, and 3% and 0 for BKVN, respectively. In the fast metabolism group, the incidence of BK virenia was significantly higher than that in the slow metabolism group (P=0.02). The incidence of BK viruria and BKVN did not significantly differ between two groups (both P>0.05). Conclusions According to the CYP3A5 genotyping outcomes, the recipients with a high metabolic rate of FK506 have a high risk of BK viremia early after renal transplantation.

Objective To investigate the clinical characteristics of DCD donor-derived CRKP infection and bleeding in kidney transplantation,and to summarize the experience of diagnosis,treatment and prevention.Methods A retrospective analysis was carried out from July 2016 to December 2017 in hospital,containing clinical data of 4 cases of CRKP-infected DCD donors and 7 cases of kidney transplantation recipients.Results In the CRKP culture of 4 cases of DCD donors,1 case was positive for blood culture,1 case was positive for urine culture,1 case was positive for sputum culture,and 1 case was negative for blood,urine and sputum culture.The corresponding 7 recipients were all positive for blood culture after renal transplantation,4 cases were positive for urine culture,3 cases were positive for sputum culture,and 5 cases were positive for perirenal drainage.Of the 7 patients,4 cases had renal artery hemorrhage,1 of them was died.The average bleeding time was 17.75 days after operation (14-19 days).In 7 patients with renal transplantation,CRP increasd.And in 3 cases of deaths,CRP was stably higher than normal.Meanwhile,CRP in 4 surviving patients gradually decreased to the normal range after effective anti-infection treatment.All 7 patients were treated with carbapenems;2 patients were dead without avibactam therapy;and 5 cases were treated with avibactam and carbapenems and survived,1 case died and 1 case had good renal function recovery.Conclusion Positive CRKP in blood,urine and sputum of DCD donors can lead to CRKP infection in kidney transplant recipients.Even if the body fluids of donors are all negative,the false negative results could not be excluded.Persistent or increased high-level CRP after operation is an early warning on CRKP infection.And CRP can be used as an indicator for evaluating the effectiveness of anti CRKP therapy.The combination of avibactam and carbapenem antibiotics is an effective regimen in the treatment of DCD donor-derived CRKP.

Objective To investigate the characteristics and manifestations of the different stages of BK virus infection in the recipients after renal transplantation.Methods A retrospective survey from January 2015 to December 2016 was done in our hospital.A total 135 recipients were included and accepted BK virus detection in 1,3,6,9,12,15 months respectively after renal transplantation.The prevalence of decoy cell,BK virus DNA load in urine and BK virus DNA load in blood was 56 cases (41.5％),9 cases (43.7％) and 30 cases (22.2％),5 cases of BK vims nephropathy confirmed by pathological biopsy (3.7％).At the same time,51 cases (37.8％) were combined with decoy cells and virus DNA load in urine.Positive decoy cells and negative BK virus DNA load in urine was 5 cases,and Positive BK virus DNA load in urine and negative decoy cells was 8 cases.The recipients were divided into positive group of urine decoy cell,positive group of urinary BK virus DNA load,and positive group of blood BK virus DNA load.Statistical correlation analysis was conducted on the laboratory test results of the 3 groups.Results The positive group of blood BK virus DNA load were detected the high level urine decoy cell count [median of 23/10HPF(2-48/10HPF)] and high level of urinary BK virus DNA load [4.52 × 106 copies/ml (6.51 × 103-7.89 × 109 copies/ml)],significantly higher than the positive group of decoy cells [8/10HPF(2-40/10HPF)] and the positive group of urine BK virus DNA load [4.56 × 105 copies/ml(5.62 × 103-7.89 ×109 copies/ml)] (P ＜ 0.05).The decoy cell count and urine DNA load has a significant linear correlation in viruria recipients,and the urinary BK DNA load and blood BK virus DNA load has the same significant 0.939 and 0.702 in 3 months,0.969 and 0.910 in 6 months,0.782 and 0.766 in 9 months,0.898 and 0.615 in 12 months after renal transplantation.Conclusions There is a linear correlation between decoy cell in urine,viruria and viremia,suggesting that the infection of BK virus in kidney transplant recipients is a continuous process.linear correlation in viremia recipients(P ＜ 0.05).The correlation coefficients at different time points were

Objective To investigate the clinical characteristics and risk factors of the incidence of herpes zoster after renal transplantation. Methods Clinical data of 830 recipients undergoing renal transplantation for the first time in the Organ Transplantation Research Institute of the 309th Hospital of Chinese People's Liberation Army from March 2009 to March 2012 were retrospectively analyzed. Univariate and multivariate Logistic regression analyses were performed to identify the risk factors of the incidence of herpes zoster after renal transplantation. Results Among 830 patients, 42 (5.1%) suffered from herpes zoster postoperatively. Clinical manifestations of herpes zoster mainly included varicella-zoster rash in the head, face, trunk and limbs. No patient died from herpes zoster. Post-herpetic neuralgia (PHN) was the most common complication of herpes zoster. Univariate Logistic regression analysis revealed that advanced age and adrenal cortical hormone (hormone) shock therapy could increase the risk of herpes zoster viral infection after renal transplantation (OR=2.414, P=0.016; OR=2.936, P=0.003). Multivariate Logistic regression analysis demonstrated that advanced age and hormone shock therapy were the independent risk factor of the incidence of herpes zoster following renal transplantation (OR=2.238, P=0.030; OR=2.755, P=0.005). Conclusions Herpes zoster after renal transplantation is clinically manifested with varicellazoster rash. Advanced age and hormone shock therapy are the independent risk factor of the incidence of herpes zoster after renal transplantation.

Objective To evaluate the effect of extracorporeal photopheresis upon the expression levels of interleukin (IL)-12p70 and T helper cell (Th) 1/Th2-like cytokines in splenic lymphocytes of mouse models undergoing skin transplantation. Methods The C57BL/6 mice were used as the donors and BALB/c mice as the recipients to establish mouse models with skin allograft. The splenic lymphocytes in the C57BL/6 and BALB/c mice (CSP and BSP) were isolated and treated with 8-methoxypsoralen combined long-wave ultraviolet (PUVA-SP). According to the components of intravenous infusion into the recipients, all experimental animals were randomly divided into the PUVA-BSP, PUVA-CSP, BSP, CSP and phosphate buffer solution (PBS) control groups (n=12 for each group). The mice were injected with PUVA-BSP, PUVA-CSP, BSP, CSP or PBS via the caudal vein at preoperative 7 d, upon the day of surgery and at postoperative 7 d, respectively. The apoptosis of the splenic lymphocytes was observed after PUVA treatment. The expression levels of IL-12p70 and Th1/Th2-like cytokines in the peripheral blood of the recipients were quantitatively measured. Results After the skin transplantation, the expression levels of IL-12p70 in the peripheral blood of mice in the PUVA-BSP and PUVA-CSP groups were significantly down-regulated compared with those in the BSP, CSP and PBS control groups (all P<0.01). In the PUVA-BSP and PUVA-CSP groups, the expression levels of Th1-like cytokine IL-2, interferon (IFN)-γwere dramatically lower than those in the BSP, CSP and PBS control groups (all P<0.01). The expression levels of Th2-like cytokine IL-10 in the PUVA-BSP and PUVA-CSP groups were significantly up-regulated compared with those in the BSP, CSP and PBS control groups (all P<0.01). Conclusions Infusion of PUVA-SP at a sufficient dose can induce the low expression level of IL-12p70 and drive the incidence of Th2 immune deviation in the recipient BALB/c mice.

Objective To analyze and discuss the dynamics of cellular immune response to persistent infection with BK virus after renal transplantation.Methods The recipients of renal transplantation in our center were selected and BK virus load in urine and blood was regularly observed.The victims of persistent infection with BK virus (defined as two successive positive results of BK virus load in urine or blood) were followed up and peripheral blood mononuclear cells (PBMCs) were collected for mixed cultivation with overlapping peptide pool,which contained peptide fragments (VP1,VP2,VP3,LT-Ag and st-Ag) extracted from BK virus.Flow cytometry was used to examine the in vitro proliferation of IFN-γ/IL-2/TNF-ininduced T cells and analyze the dynamics of cellular immune response to BK virus.Results A total of 46 recipients of renal transplantation were enrolled and 6 victims of persistent viruria were identified.Of the 6 victims,3 were complicated with persistent viremia,and 2 were diagnosed as BK virus nephropathy by biopsy,presenting with persistent viruria and viremia.The victims of persistent BK viremia after renal transplantation showed a significantly decreasing trend in cellular immune response to 5 BKV-specific proteins,according to the proliferation of TNF-γ/IL-2/TNF-α-induced T cells.However,this trend was not observed in the victims of persistent BK viruria.Conclusion At the stage of viremia,the victims of BKV infection after renal transplantation have seriously inhibited specific immune response to BKV.Thus,if the antiviral mechanisms are not restored in time,these recipients suffering persistent viremia are prone to virus nephropathy (BKVN),delayed graft function,and even graft loss.