器官移植

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Expert Forum

Management of immunosuppressive drugs in HIV-positive solid organ transplant recipients

Shao Kun, Wang Xianghui, Zhou Peijun

, Available online , doi: 10.3969/j.issn.1674-7445.2024009

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Abstract:
The application of combination antiretroviral therapy (cART) has significantly prolonged the life expectancy of patients infected with human immunodeficiency virus (HIV). However, viral infection and adverse reactions of cART drugs make patients more prone to organ failure. Solid organ transplantation (SOT) has become a standard treatment for HIV-infected patients with end-stage organ failure. Nevertheless, among HIV-positive SOT recipients, multiple problems remain to be resolved, such as increased incidence of graft rejection, increased infection risk, drug toxicity and drug interaction between cART therapy and immunosuppressive drugs, etc. It is extremely challenging to deliver appropriate management for HIV-positive SOT recipients. Therefore, the application of immune induction therapy, calcineurin inhibitors, mammalian target of rapamycin (mTOR) inhibitors and other immunosuppressive drugs in HIV-positive SOT recipients was reviewed, aiming to provide reference for subsequent related studies.

Exploratory road of liver xenotransplantation: from scientific research to clinical application

Li Xiao, Cao Weiwei, Yu Liang

, Available online , doi: 10.3969/j.issn.1674-7445.2024043

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With the advancement of surgical technologies and the improvement of perioperative management, the survival rates of organ transplant recipients and grafts have been significantly elevated. Shortage of donor organs has become the main obstacle to further development of organ transplantation. Recently, kidney and heart xenotransplantation with genetically modified pigs as donors have entered clinical trials and achieved favorable results. Xenotransplantation has repeatedly become a hot spot in biomedical research. Compared with heart and kidney, the survival time of liver grafts from genetically modified pigs in non-human primates is shorter. Besides, experimental results are dramatically different. Hence, it is not eligible for clinical trials. Consequently, recent research progress in xenotransplantation was reviewed from surgical pattern selection, coagulation dysfunction and acute vascular rejection, advances in liver xenotransplantation were summarized, and the main problems hindering xenotransplantation from entering clinical trials and potential solutions were illustrated, aiming to provide reference for xenotransplantation from scientific research to clinical application.

Hypomagnesemia and kidney transplantation: research progress in immune effect and infection risk

Hu Yao, Liu Ling

, Available online , doi: 10.3969/j.issn.1674-7445.2024029

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As a cation with abundant intracellular contents and extensive functions, magnesium plays an active role in immune function and captivates widespread attention. Under the influence of multiple factors, such as use of calcineurin inhibitors, hypomagnesemia post-kidney transplantation is not uncommon. Infection is a common complication post-kidney transplantation and one of the main causes of death of kidney transplant recipients. Recent clinical studies have shown that hypomagnesemia post-kidney transplantation is closely associated with the risk of infection post-transplantation. Emphasizing and monitoring magnesium concentration in kidney transplant recipients may help prevent infection and improve clinical prognosis of both recipients and grafts. Therefore, research progress in magnesium and immune response, the causes of hypomagnesemia post-kidney transplantation and hypomagnesemia and infection post-kidney transplantation was reviewed, aiming to provide reference for the prevention and treatment of infection post-kidney transplantation.

, Available online

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Editorial

Optimization of immunosuppressive regimen for kidney transplant recipients

Dong Zhen, Wang Hongyang

, Available online , doi: 10.3969/j.issn.1674-7445.2024087

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With the maturity and development of surgical techniques, as well as the improvement of perioperative management level, the success rate of kidney transplantation has been significantly improved. However, due to evident differences in heredity and antigenicity between donors and recipients, rejection will occur after kidney transplantation, which will affect the survival of renal grafts. Immunosuppression is an important treatment for rejection, which is of significance to reduce the risk of rejection and enhance graft survival rate. Nevertheless, immunosuppressants may cause multiple complications while lowering the incidence of rejection, such as infection, cardiovascular diseases and tumors, etc., which seriously affect the quality of life of patients and may even lead to their death. Reasonable selection of immunosuppressants and continuous optimization of immunosuppressive regimen for recipients play a critical role in improving the survival of recipients and renal grafts. In this article, the development history of organ transplantation, immune induction therapy and immune maintenance therapy was reviewed, and the progress in the optimization of immunosuppressive regimens for kidney transplant recipients was discussed, aiming to provide reference for improving clinical prognosis of kidney transplant recipients.

Review Article

Development course and research status of incisions in lung transplantation

Xu Jian, Shao Jingbo, Chen Yuan, Wei Dong, Ye Shugao, Chen Jingyu

, Available online , doi: 10.3969/j.issn.1674-7445.2024048

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Surgical technique of lung transplantation exerts significant impact on clinical prognosis of the recipients. Choosing an appropriate surgical incision determines the exposure of intraoperative visual field, which is the first step of surgical success and directly affects subsequent surgical procedures. Lung transplantation incision is usually considered as primary closure. Nevertheless, for patients with high-risk factors such as oversized lung allografts and primary graft failure after lung transplantation, primary closure cannot be achieved. Hence, delayed chest closure is an effective strategy. The selection of incisions and the adoption of delayed chest closure of lung transplantation exert profound impact upon perioperative prognosis, long-term quality of life and surgical complications of the recipients. Therefore, the development and research status of Clamshell incision, anterolateral incision, posterolateral incision and median sternal incision in lung transplantation were reviewed, highlighting the effect of incision patterns on clinical prognosis of lung transplantation and providing reference for the selection of incisions in clinical lung transplantation.

Re-understanding of the clinical application value of dopamine in kidney transplantation

Zhong Yuqi, Wang Yuchen, Miao Yun

, Available online , doi: 10.3969/j.issn.1674-7445.2024030

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Dopamine is the precursor of biosynthesis of norepinephrine. Low-dose dopamine mainly excites dopamine receptors, which may dilate renal and mesenteric vessels, increase renal blood flow and improve the microcirculation. In recent years, low-dose dopamine has been widely applied in the field of kidney transplantation due to its vasoactive effect. However, with the development of evidence-based medicine, the role of dopamine in protecting the perfusion function of renal allograft in kidney transplantation has been questioned. Multiple studies have shown that dopamine brings no significant benefit to renal and cardiac function in kidney transplantation, exerts low pressor effect, and may even increase the risk of perioperative complications. Norepinephrine may be used as a safe substitute. In this article, recent progress in the effect of dopamine upon renal and cardiac function and hemodynamics during kidney transplantation was reviewed, aiming to provide reference for clinical application of dopamine in kidney transplantation.

Original Article

Clinical characteristics and risk factors of 209 cases of urinary tract infection after kidney transplantation

Wang Peiyu, Ding Handong, Zhong Jinbiao, Liao Guiyi, Liang Chaozhao

, Available online , doi: 10.3969/j.issn.1674-7445.2024095

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Objective To investigate clinical characteristics and risk factors of different stages of urinary tract infection after kidney transplantation. Methods Clinical data of 209 kidney transplant recipients were retrospectively analyzed. According to time points of postoperative follow-up, all recipients were divided into 3 stages: within 1 month post-kidney transplantation, 1-6 months post-kidney transplantation, and 7-12 months post-kidney transplantation. The incidence of urinary tract infection, urine culture results of recipients with urinary tract infection and drug resistance characteristics of common pathogens during different stages after kidney transplantation were analyzed. The strains of patients with recurrent urinary tract infection were identified. The risk factors of urinary tract infection and the effect of urinary tract infection on renal allograft function were analyzed. Results The urinary tract infection rate was 90.0% in the first stage, 49.3% in the second stage and 22.5% in the third stage. The urinary tract infection rates of male recipients undergoing living-related organ donation in the second and third stages were lower than those of female recipients (both P＜0.05). Urine culture test yielded positive results in 60 cases, and 84 strains of pathogenic bacteria were detected, mainly Gram-negative bacteria, among which Klebsiella pneumoniae accounted for the highest proportion. Sixty-six recipients had recurrent urinary tract infection, and the detected pathogens included Klebsiella pneumoniae, Escherichia coli and Candida glabrata, etc. Univariate analysis showed that postoperative use of antithymocyte globulin was the risk factor for urinary tract infection in the first stage. Preoperative urinary tract infection and donor type were the risk factors for urinary tract infection in the second stage. Gender and age of the recipients were the risk factors for urinary tract infection in the third stage. Multivariate analysis revealed that postoperative use of antithymocyte globulin was the risk factor for urinary tract infection in the first stage. Gender and age of the recipients were the risk factors for urinary tract infection in the third stage (all P＜0.05). In the third stage, 65 cases were cured and 38 cases were not cured. There were no significant differences in serum creatinine level and white blood cell count in the untreated recipients before and after corresponding treatment (both P＜0.05). Conclusions Gram-negative bacteria are the main pathogens of urinary tract infection in kidney transplant recipients, and drug resistance is relatively high. Postoperative use of antithymocyte globulin, female and old age are the risk factors for urinary tract infection in kidney transplant recipients.

Effect of preoperative metabolic syndrome on early function of renal allografts in kidney transplant recipients

Tang Yongbin, Tian Zijian, Zhang Zhipeng, Wang Jinfu, Liu Ming, Zhang Yaqun

, Available online , doi: 10.3969/j.issn.1674-7445.2024045

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Objective To evaluate the effect of preoperative metabolic syndrome on early function of renal allografts in allogeneic kidney transplant recipients. Methods Clinical data of 117 allogeneic kidney transplant recipients were retrospectively analyzed. According to the renal allograft function, they were divided into the delayed graft function (DGF) group (n=29) and non-DGF group (n=88). Relevant risk factors of DGF in recipients undergoing allogeneic kidney transplantation were assessed by univariate and multivariate regression analyses. The effect of preoperative metabolic syndrome on early function of renal allografts was analyzed. Results Among 117 kidney transplant recipients, 47 cases were complicated with preoperative metabolic syndrome, and 29 cases developed postoperative DGF. In the DGF group, 83% of the recipients were complicated with preoperative metabolic syndrome, higher than 74% in the non-DGF group (P<0.05). Univariate analysis showed that the body mass index (BMI) and terminal serum creatinine (Scr) level of the donors, and BMI, blood glucose level, triglyceride level and the proportion of preoperative metabolic syndrome of the recipients in the DGF group were higher than those in the non-DGF group (all P<0.05). Multivariate logistic regression analysis revealed that high Scr levels of the donors, high hemoglobin levels of the recipients and preoperative metabolic syndrome of the recipients were the independent risk factors for DGF after kidney transplantation (all P<0.05). Conclusions Preoperative metabolic syndrome is an independent risk factor for DGF in allogeneic kidney transplant recipients. Corresponding measures should be taken to lower the incidence of DGF and other metabolic complications.

Study of adverse drug events related to tacrolimus in pediatric solid organ transplant recipients based on FEARS database

Dong Boqing, Wang Jingwen, Bi Huanjing, Chen Zuhan, Lu Cuinan, Xue Wujun, Li Yang, Ding Xiaoming

, Available online , doi: 10.3969/j.issn.1674-7445.2024031

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Objective To investigate the characteristics of adverse drug events (ADEs) related to tacrolimus (Tac) in pediatric solid organ transplant recipients. Methods The data were retrieved from Food and Drug Administration Adverse Event Reporting System database from the first quarter of 2004 to the second quarter of 2023. The ADEs data of pediatric organ transplant recipients with Tac as the primary suspected drug were extracted. The relationship between Tac and ADEs was quantitatively analyzed by proportional imbalance method. Basic characteristics and signal strength of ADEs related to Tac were analyzed. ADEs related to Tac in children of different ages and different types of organ transplantation were analyzed. Results A total of 1 443 children's ADEs reports involving Tac were screened, including 188 cases (13.0%) of heart transplantation, 668 cases (46.3%) of liver transplantation, 531 cases (36.8%) of kidney transplantation and 56 cases (3.9%) of lung transplantation. The median age of children was 10 years old. The top three countries with ADEs reporting were the United States, France and the United Kingdom. China reported 26 cases, accounting for 1.8%. Infection and infectious diseases accounted for the highest proportion (21.0%) in ADEs related to Tac, including EB virus and cytomegalovirus infection, etc. Infection and infectious diseases occupied the largest proportion of ADE related to Tac in children of different ages, whereas the pathogen types were different. Rejection, unstable immunosuppression level and renal function damage were also common ADEs related to Tac in children of all ages. Nervous system disease was the main ADE in heart transplant recipients, while infection and infectious diseases were more common in liver and kidney transplant recipients. Rejection was the most common ADE in lung transplant recipients. Conclusions ADEs related to Tac possess different distribution characteristics in different types of organ transplantation. Extensive attention should be paid to individualized drug monitoring and risk assessment in pediatric organ transplant recipients, thereby optimizing Tac treatment and reducing the risk of ADEs.

Correlation between metabolic markers and blood lipid levels in kidney transplant recipients

Xu Yuan, Hou Shuang, Chen Qian, Niu Yulin, Li Haiyang

, Available online , doi: 10.3969/j.issn.1674-7445.2024014

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Objective To analyze the co-expressed genes in blood lipid metabolism, hyperlipidemia and tacrolimus metabolism and their correlation with blood lipid levels in kidney transplant recipients. Methods Co-expressed genes were screened from Comparative Toxicogenomic Database (CTD). Baseline data of 25 kidney transplant recipients were collected. The expression levels of ATP binding cassette subfamily A member 1(ABCA1), peroxisome proliferator activated receptor γ (PPAR-γ) and glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1) were measured. All recipients were followed up. The concentrations of fasting blood glucose, glycosylated hemoglobin, triglyceride, total protein, albumin, globulin, cholesterol, high-density lipoprotein, low-density lipoprotein and tacrolimus blood concentration were collected at postoperative 1, 3, 6 and 12 months, and the incidence of hyperlipidemia in the recipients was analyzed. The correlation between ABCA1, GPIHBP1, PPAR-γ and clinical indexes was assessed. The diagnostic efficiency of related indexes for hyperlipidemia after kidney transplantation was evaluated. Results Three co-expressed genes including ABCA1, PPAR-γ and GPIHBP1 were screened. ABCA1 was positively correlated with cholesterol level at postoperative 6 months and tacrolimus blood concentration at postoperative 3 months, whereas negatively correlated with fasting blood glucose level at postoperative 3 months (all P<0.05). GPIHBP1 was negatively correlated with preoperative cholesterol and triglyceride levels, whereas positively correlated with tacrolimus blood concentration at postoperative 3 months (all P<0.05). PPAR-γ was negatively correlated with preoperative globulin and low-density lipoprotein levels (both P<0.05). ABCA1, GPIHBP1 and PPAR-γ combined with globulin and blood glucose level at postoperative 1 and 6 months after operation yielded high diagnostic efficiency for hypertriglyceridemia after kidney transplantation (AUC=0.9). ABCA1, GPIHBP1 and PPAR-γ combined with tacrolimus blood concentrations at postoperative 1 and 6 months and blood glucose level at postoperative 6 months had high diagnostic efficiency for hypercholesterolemia after kidney transplantation (AUC=0.931). Conclusions ABCA1, GPIHBP1 and PPAR-γ are correlated with blood lipid level and tacrolimus blood concentration after kidney transplantation to different degrees. No definite evidence has been supported for predicting hyperlipidemia after kidney transplantation. Immunity improvement and rational blood glucose management may be beneficial factors for hyperlipidemia control.

Evaluation of the predictive ability of individualized drug administration adjuvant decision-making system JPKD for tacrolimus blood concentration in kidney transplant recipients

Yan Hui, Wu Furong, Ji Peng, Shen Aizong, Zhang Shengyu

, Available online , doi: 10.3969/j.issn.1674-7445.2024011

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Objective To evaluate the predictive ability and influencing factors of individualized drug administration adjuvant decision-making system Java PK^® for Desktop (JPKD) for tacrolimus blood concentration in kidney transplant recipients. Methods The monitoring data of tacrolimus blood concentration from 149 recipients early after kidney transplantation were collected. The trough blood concentration of tacrolimus was predicted by JPKD. The absolute weighted deviation and relative prediction deviation between the actual and predicted concentration were calculated. The influencing factors of the absolute weighted deviation were analyzed by univariate and multivariate logistic regression analyses, and the predictive values of these influencing factors on the accuracy of software prediction were assessed by delineating the receiver operating characteristic (ROC) curve. Results 266 samples of tacrolimus blood concentration data were collected from 149 patients. The measured blood concentration of tacrolimus was (6.5±3.0) ng/mL (1.1-16.6 ng/mL), and the predicted value calculated by JPKD was (5.6±2.5) ng/mL (1.4-14.4 ng/mL). The absolute weighted deviation of the calculated data was 28.38%, and the relative prediction deviation was −13.55%. Univariate analysis showed that gender, albumin, changes in hematocrit, cytochrome P450 (CYP)3A5*3 genotype and C3435T genotype were associated with the inaccurate prediction results. Multivariate logistic regression analysis found that CYP3A5*3 genotype of AA and the changes in hematocrit were the independent risk factors affecting the accuracy of tacrolimus blood concentration predicted by JPKD. ROC curve analysis showed that when the changes in hematocrit exceeded 2.25%, the risk of inaccurate software prediction was increased. Conclusions JPKD possesses certain accuracy in predicting the blood concentration of tacrolimus in kidney transplant recipients, which may improve the qualified rate of tacrolimus blood concentration. Nevertheless, CYP3A5*3 genotype and the changes of hematocrit may affect the accuracy of predictions.

Transplantation Forefront

Research progress in tolerogenic dendritic cells in immune tolerance of liver transplantation

Yang Zhiqi, Li Minghao

, Available online , doi: 10.3969/j.issn.1674-7445.2024039

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Rejection after liver transplantation severely affects the survival of recipients. Long-term use of immunosuppressants is an important approach to prevent rejection, whereas it may cause toxic effects and increase the risk of adverse events such as systemic infection and tumor recurrence, etc. Therefore, before successful liver transplantation, how to induce individual immune tolerance of recipients and achieve complete or early withdrawal of postoperative immunosuppressants remains to be investigated by practitioners of organ transplantation. In recent years, certain progresses have been made in the mechanism of immune tolerance induced by tolerogenic dendritic cells in liver transplantation, and preliminary outcomes have been obtained in clinical trials. In this article, basic research and clinical application progress in the characteristics of tolerogenic dendritic cells, the mechanism underlying participating in liver immune microenvironment remodeling, and inducing immune tolerance in liver transplantation were reviewed, aiming to provide reference for the application of tolerogenic dendritic cells in immune tolerance of liver transplantation.