OBJECTIVE: To investigate the causes of graft loss in kidney transplant recipients. METHODS: We retrospectively analyzed the clinical data of 135 recipients with graft loss after renal transplantation in the Eighth Medical Center of Chinese PLA General Hospital from January 1, 2002 to January 1, 2022. RESULTS: A total of 135 kidney transplant recipients experienced graft failure. The causes of graft loss included graft rejection (70 cases, 51.8%), death of the recipients with functional graft (37 cases, 27.4%), surgical complications (12 cases, 8.9%), drug toxicity (4 cases, 3.0%), carbapenem-resistant Klebsiella pneumoniae infection (4 cases, 3.0%), polyoma BK virus-related nephropathy (3 cases, 2.2%), primary nonfunctioning kidney (2 cases, 1.5%), recurrence of primary disease (2 cases, 1.5%), and prerenal acute renal failure (1 case, 0.7%). CONCLUSION The main cause of graft loss after renal transplantation is graft rejection, and the secondary cause is death of the recipient with functional graft, and other reasons can be rare.
Humans ; Graft Rejection ; Kidney Transplantation/adverse effects* ; Retrospective Studies

OBJECTIVE: To investigate the inhibitory effect of AZD2014, a dual mTORC1/2 inhibitor, against acute graft rejection in a rat model of allogeneic liver transplantation. METHODS: Liver transplantation from Lewis rat to recipient BN rat (a donor-recipient combination that was prone to induce acute graft rejection) was performed using Kamada's two-cuff technique. The recipient BN rats were randomized into 2 groups for treatment with daily intraperitoneal injection of AZD2014 (5 mg/kg, n=4) or vehicle (2.5 mL/kg, n=4) for 14 consecutive days, starting from the first day after the transplantation. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) levels of the rats were measured 3 days before and at 1, 3, 5, 7, 10, and 14 days after the transplantation, and the survival time of the rats within 14 days were recorded. Immunohistochemical staining was used to examine the expressions of CD3 and Foxp3 in the liver graft, and acute graft rejection was assessed using HE staining based on the Banff schema. RESULTS: Three rats in the control group died within 14 days after the surgery, while no death occurred in the AZD2014 group, demonstrating a significantly longer survival time of the rats in AZD2014 group (χ²=4.213, P=0.04). Serum ALT, AST and TBIL levels in the control group increased progressively after the surgery and were all significantly higher than those in AZD2014 group at the same time point (P < 0.05). Pathological examination revealed significantly worse liver graft rejection in the control group than in AZD2014 group based on assessment of the rejection index (P < 0.01); the rats in the control group showed more serious T lymphocyte infiltration and significantly fewer Treg cells in the liver graft than those in AZD2014 group (P < 0.01). CONCLUSIONS AZD2014 can effectively inhibit acute graft rejection in rats with allogeneic liver transplantation.
Animals ; Benzamides ; Graft Rejection/prevention & control* ; Graft Survival ; Liver/pathology* ; Liver Transplantation ; Mechanistic Target of Rapamycin Complex 1 ; Morpholines ; Pyrimidines ; Rats ; Rats, Inbred Lew

BACKGROUND: Although ABO-incompatible (ABOi) kidney transplantation (KT) has been performed successfully, a standard preconditioning regimen has not been established. Based on the initial antidonor ABO antibody titers, an individualized preconditioning regimen is developed, and this study explored the efficacy and safety of the regimen. METHODS: From September 1, 2014, to September 1, 2020, we performed 1668 consecutive living-donor KTs, including 100 ABOi and 1568 ABO-compatible (ABOc) KTs. ABOi KT recipients (KTRs) with a lower antibody titer (≤1:8) were administered oral immunosuppressive drugs (OIs) before KT, while patients with a medium titer (1:16) received OIs plus antibody-removal therapy (plasma exchange/double-filtration plasmapheresis), patients with a higher titer (≥1:32) were in addition received rituximab (Rit). Competing risk analyses were conducted to estimate the cumulative incidence of infection, acute rejection (AR), graft loss, and patient death. RESULTS: After propensity score analyses, 100 ABOi KTRs and 200 matched ABOc KTRs were selected. There were no significant differences in graft and patient survival between the ABOi and ABOc groups (P  = 0.787, P  = 0.386, respectively). After using the individualized preconditioning regimen, ABOi KTRs showed a similar cumulative incidence of AR (10.0% υs . 10.5%, P  = 0.346). Among the ABOi KTRs, the Rit-free group had a similar cumulative incidence of AR ( P  = 0.714) compared to that of the Rit-treated group. Multivariate competing risk analyses revealed that a Rit-free regimen reduced the risk of infection (HR: 0.31; 95% CI: 0.12-0.78, P  = 0.013). Notably, antibody titer rebound was more common in ABOi KTRs receiving a Rit-free preconditioning regimen ( P  = 0.013) than those receiving Rit. ABOi KTRs with antibody titer rebound had a 2.72-fold risk of AR (HR: 2.72, 95% CI: 1.01-7.31, P  = 0.048). ABOi KTRs had similar serum creatinine and estimated glomerular filtration rate compared to those of ABOc KTRs after the first year. CONCLUSIONS An individualized preconditioning regimen can achieve comparable graft and patient survival rates in ABOi KT with ABOc KT. Rit-free preconditioning effectively prevented AR without increasing the risk of infectious events in those with lower initial titers; however, antibody titer rebound should be monitored.
Humans ; Kidney Transplantation/adverse effects* ; Living Donors ; Kidney ; Immunosuppressive Agents/therapeutic use* ; Rituximab/therapeutic use* ; ABO Blood-Group System ; Graft Rejection ; Graft Survival

Objective: To evaluate the short-and mid-term efficacy of pediatric kidney transplantation and the risk factors for kidney graft and recipient. Methods: The baseline data and postoperative complications of pediatric donors and recipients of 284 kidney transplants were retrospectively analyzed in the Department of Kidney Transplantation in the First Affiliated Hospital of Zhengzhou University from August 2010 to May 2021 and all subjects were followed up until December 31, 2021. According to the survival status of donors and recipients, they were divided into the graft-loss group and the graft-survival group, and the recipient death group and survival group, respectively. Univariate comparison between groups was performed by Log-rank test, and Cox proportional risk model was used to explore the independent risk factors for the graft and recipient survival. Results: Among the 284 children recipients, 184 cases (64.8%) were male and 100 cases(35.2%) were female, and 19 cases (6.7%) were living relative donor renal transplantation, 19 cases (6.7%) were preemptive transplantation, and 8 cases were secondary transplantation. The age of 284 recipients at the time of transplantation was 13.0 (9.0, 15.0) years, among whom 29 cases aged 0-6 years, 96 cases aged 7-11 years old, and 159 cases aged 12-18 years. The 1, 3, and 5 year survival rates were 92.3%, 88.9% and 84.8% for the kidney grafts, and were 97.1%, 95.6% and 94.4% for the recipients, respectively. Multivariate analysis showed postoperative acute rejection (HR=3.14, 95%CI 1.38-7.15, P=0.006) and perioperative vascular complications (HR=4.73, 95%CI 2.03-11.06, P<0.001) were independent risk factors for the survival of kidney graft. Postoperative infection (HR=14.23, 95%CI 3.45-58.72, P<0.001) was an independent risk factor for the postoperative mortality of recipients. Conclusions: Pediatric kidney transplantation shows a good short-and mid-term prognosis. Postoperative acute rejection and perioperative vascular complications are the risk factors for the survival of kidney graft, and postoperative infection is the risk factor affecting the survival of recipient.
Child ; Female ; Graft Rejection ; Graft Survival ; Humans ; Kidney Transplantation/adverse effects* ; Living Donors ; Male ; Postoperative Complications ; Prognosis ; Retrospective Studies ; Risk Factors

BACKGROUND: The complement system plays an important role in the immune response to transplantation, and the diagnostic significance of peritubular capillary (PTC) C4d deposition (C4d+) in grafts is controversial. The study aimed to fully investigate the risk factors for PTC C4d+ and analyze its significance in biopsy pathology of kidney transplantation. METHODS: This retrospective study included 124 cases of kidney transplant with graft biopsy and donor-specific antibody (DSA) testing from January 2017 to December 2019 in a single center. The effects of recipient pathological indicators, eplet mismatch (MM), and DSAs on PTC C4d+ were examined using univariate and multivariate logistic regression analyses. RESULTS: In total, 35/124 (28%) were PTC C4d+, including 21 with antibody-mediated rejection (AMR), eight with renal tubular injury, three with T cell-mediated rejection, one with glomerular disease, and two others. Univariate analysis revealed that DSAs (P < 0.001), glomerulitis (P < 0.001), peritubular capillaritis (P < 0.001), and human leukocyte antigen (HLA) B eplet MM (P = 0.010) were the influencing factors of PTC C4d+. According to multivariate analysis, DSAs (odds ratio [OR]: 9.608, 95% confidence interval [CI]: 2.742-33.668, P < 0.001), glomerulitis (OR: 3.581, 95%CI: 1.246-10.289, P = 0.018), and HLA B eplet MM (OR: 1.166, 95%CI: 1.005-1.353, P = 0.042) were the independent risk factors for PTC C4d+. In receiver operating characteristic curve analysis, the area under the curve was increased to 0.831 for predicting PTC C4d+ when considering glomerulitis, DSAs, and HLA B eplet MM. The proportions of HLA I DSAs and PTC C4d+ in active antibody-mediated rejection were 12/17 and 15/17, respectively; the proportions of HLA class II DSAs and PTC C4d+ in chronic AMR were 8/12 and 7/12, respectively. Furthermore, the higher the PTC C4d+ score was, the more serious the urinary occult blood and proteinuria of recipients at the time of biopsy. CONCLUSIONS PTC C4d+ was mainly observed in AMR cases. DSAs, glomerulitis, and HLA B eplet MM are the independent risk factors for PTC C4d+.
Allografts ; Biopsy ; Complement C4b ; Graft Rejection ; HLA Antigens ; HLA-B Antigens ; Humans ; Kidney Transplantation/adverse effects* ; Peptide Fragments ; Retrospective Studies ; Risk Factors

Antibody-mediated rejection (AMR) is a rare and serious complication after lung transplantation, with no characteristic of pathological manifestation, no systematic standard treatment, and the poor efficacy and prognosis. We reported a case of early AMR after lung transplantation and the relevant literature has been reviewed. A male patient presented with symptoms of cold 99 days after transplantation and resolved after symptomatic treatment. He admitted to the hospital 14 days later because of a sudden dyspnea and fever. Anti-bacteria, anti-fungi, anti-virus, and anti-pneumocystis carinii treatment were ineffective, and a dose of 1 000 mg methylprednisolone did not work too. The patient's condition deteriorated rapidly and tracheal intubation was done to maintain breathing. Serum panel reactive antibody and donor specific antibody showed postive in humen leukocyte antigen (HLA) II antibody. Pathological examination after transbronchial transplantation lung biopsy showed acute rejection. Clinical AMR was diagnosed combined the donor-specific antibody with the pathological result. The patient was functionally recovered after combined treatment with thymoglobuline, rituximab, plasmapheresis, and immunoglobulin. No chronic lung allograft dysfunction was found after 3 years follow up. We should alert the occurrence of AMR in lung transplantation recipient who admitted to hospital with a sudden dyspnea and fever while showed no effect after common anti-infection and anti-rejection treatment. Transbronchial transplantation lung biopsy and the presence of serum donor-specific antibody are helpful to the diagnosis. The treatment should be preemptive and a comprehensive approach should be adopted.
Graft Rejection ; Graft Survival ; HLA Antigens ; Humans ; Isoantibodies ; Lung Transplantation/adverse effects* ; Male

graft survival following primary penetrating keratoplasty (PK) with imported donor corneas.METHODS: The eyes of patients who underwent primary PK with imported donor corneas were classified retrospectively into two groups according to a donor-age cutoff of 65 years. Primary outcome measures were rejection-free graft survival and graft survival. Cox proportional hazard regression analysis was used to assess the factors affecting graft survival. Survival analysis was performed using the Kaplan-Meier method, while differences between groups were examined using a log-rank test. A subgroup analysis of low- and high-risk eyes according to preoperative diagnosis was also performed.RESULTS: A total of 140 eyes from 138 patients (age, 58 ± 18 years) were enrolled. Cox regression analysis revealed that the donor age of 65 years or older group presented an increased risk of both graft rejection and failure. Survival analysis revealed that rejection-free graft survival and graft survival rates were higher in eyes in the donor age of less than 65 years group. Finally, in the subgroup analysis, both rejection-free graft survival and graft survival rates were significantly higher in the donor age of less than 65 years group than in the donor age of 65 years or older group, but only in the low-risk subgroup.CONCLUSIONS: Donor age may correlate with graft survival in primary PK performed with imported donor corneas. Donor age could be a considerable factor in primary PK with imported donor corneas, especially in preoperatively low-risk patients.]]>
Cornea ; Corneal Transplantation ; Diagnosis ; Graft Rejection ; Graft Survival ; Humans ; Keratoplasty, Penetrating ; Methods ; Outcome Assessment (Health Care) ; Retrospective Studies ; Risk Factors ; Tissue Donors ; Transplants

PURPOSE: We aimed to examine associations between right bundle branch block (RBBB) following heart transplantation (HT) and graft rejection. MATERIALS AND METHODS: We investigated 51 patients who underwent endomyocardial biopsies, electrocardiogram, right-side cardiac catheterization, and echocardiography at 1 month and 1 year after HT. We classified patients into four groups according to the development of RBBB, based on electrocardiogram at 1 month and 1 year: 1) sustained RBBB, 2) disappeared RBBB, 3) newly developed RBBB, and 4) sustained non-RBBB. The RBBB was defined as an RSR' pattern in V1 with a QRS duration ≥100 ms on electrocardiogram. RESULTS: The newly developed RBBB group (n=13, 25.5%) had a higher rate of new onset graft rejection (from grade 0 to grade ≥1R, 30.8% vs. 10.0% vs. 21.4%, p=0.042) at 1 year, compared with sustained RBBB (n=10, 19.6%) and sustained non-RBBB group (n=28, 54.9%). In contrast, the incidence of resolved graft rejection (from grade ≥1R to grade 0) was higher in the sustained RBBB group than the newly developed RBBB and sustained non-RBBB groups (70.0% vs. 7.7% vs. 25.0%, p=0.042). Left atrial volume index was significantly higher in the newly developed RBBB group than the sustained RBBB and sustained non-RBBB groups (60.6±25.9 mL/m2 vs. 36.0±11.0 mL/m2 vs. 38.4±18.1 mL/m2, p=0.003). CONCLUSION: Close monitoring for new development of RBBB at 1 year after HT, which was associated with a higher incidence of new onset graft rejection, may be helpful to identify high risk patients for graft rejection.
Biopsy ; Bundle-Branch Block ; Cardiac Catheterization ; Cardiac Catheters ; Echocardiography ; Electrocardiography ; Graft Rejection ; Heart Transplantation ; Heart ; Humans ; Incidence ; Transplants

BACKGROUND: Previous studies have recommended a 2- to 5-year waiting time prior to kidney transplantation (KT) in patients with end-stage renal disease (ESRD) and symptomatic renal cell carcinoma (RCC) and no delay for incidental early-stage RCC. Data on Asian KT recipients are unavailable.METHODS: This is a Korean single-center retrospective study on 35 KT recipients with ESRD and RCC. Patients were classified into two groups: early KT (KT performed within 1 year after nephrectomy for RCC, including KT with simultaneous nephrectomy) and delayed KT (KT performed over than 1 year after nephrectomy for RCC). Patient survival, graft survival, and cancer recurrence were compared between both groups.RESULTS: There were no statistically significant differences in patient survival (P = 0.388), graft survival (P = 0.317), or graft rejection rate (P = 0.207) between the early and delayed KT groups. Additionally, there were no differences in pathological characteristics or RCC stage other than cancer histology: acquired cystic disease-associated RCC (47.4%) was the most common RCC type in the early KT group, whereas clear cell type (62.5%) was the most common RCC type in the delayed KT group. No RCC recurrence was observed.CONCLUSION: Patients with early-stage and asymptomatic RCC do not require a mandatory observational period prior to KT after curative nephrectomy
Asian Continental Ancestry Group ; Carcinoma, Renal Cell ; Graft Rejection ; Graft Survival ; Humans ; Kidney Failure, Chronic ; Kidney Transplantation ; Kidney ; Nephrectomy ; Recurrence ; Retrospective Studies ; Transplant Recipients

OBJECTIVE: To investigate the effects of Panax notoginseng saponins (PNS) on the functional status of Kupffer cells (KCs) and immune environment after liver transplantation and explore the possible mechanisms. METHODS: KCs were isolated from rats and assessed for phagocytic activity and viability using ink and Trypan blue staining. The cells were exposed to lipopolysaccharide (LPS) alone or in combination with PNS treatment at 0, 10 or 20 μmol/L. The expressions of the inflammatory factors and the oxidative stress products in the cells and the supernatant were assayed with Western blotting and ELISA; the expression of CD206 was detected using immunofluorescence assay, and the expressions of NF-κB and Keap1-Nrf2-ARE pathway proteins were detected using Western blotting. We established an orthotopic liver transplantation (LT) model in rats and assessed the effect of 200 mg/kg PNS on the graft function, inflammatory factors, pathology of the liver tissue, hepatocyte apoptosis and survival time of the rats in comparison with those in rats receiving a sham operation or PBS treatment following LT. RESULTS: Treatment with PNS significantly lowered the levels of inflammatory factors and oxidative stress products and increased the levels of interleukin-10 (IL-10) and SOD in a concentration-dependent manner in the KCs ( < 0.05). Immunofluorescence assay showed that PNS treatment obviously increased the expression of CD206 in the KCs. PNS treatment also significantly reduced the expressions of IRAK4, p-IKK, p-IκB, p-p65 and Keap1 proteins and increased the expression levels of Nrf2 and ARE proteins in the KCs ( < 0.05). In the rat models of LT, PNS treatment significantly improved the liver graft function, lowered the expression of the pro-inflammatory factors, and reduced hepatocyte apoptosis as compared with PBS treatment. PNS treatment obviously alleviated pathological changes in the liver graft and significantly prolonged the survival time of the rats following LT ( < 0.05). In addition, injection of GdCl to block KC function resulted in severe acute graft rejection in the rats regardless of PNS treatment ( > 0.05). CONCLUSIONS PNS can reduce inflammatory response and oxidative stress in activated KCs by inhibiting NF-κB and Keap1-Nrf2-ARE pathways and promote the polarization of KCs into M2 phenotype to prolong the survival time of rats after LT.
Animals ; Graft Rejection ; Kelch-Like ECH-Associated Protein 1 ; Liver ; Liver Transplantation ; NF-E2-Related Factor 2 ; Panax notoginseng ; Rats ; Saponins