器官移植

Abstract:
Objective To discuss the clinicopathological characteristics and prognosis of the recurrence of IgA nephropathy (IgAN) after renal transplantation. Methods A total of 148 patients, pathologically diagnosed with IgAN which progressed into end-stage renal failure, undergoing renal transplantation in National Clinical Medical Research Center of Kidney Diseases, Nanjing General Hospital of Nanjing Military Command from January 1996 to April 2009, were included in this study.According to whether IgAN recurred, all patients were assigned into recurrence (n=46) and non-recurrence groups (n=102). Urinary red blood cell (U-RBC) count, 24 h urinary protein level, renal function including serum creatinine (Scr) and glomerular filtration rate (GFR) at 0, 1, 2, 3 and 5 years after renal transplantation were statistically compared between two groups. The incidence of histopathological renal injury and survival rate of transplant kidneys was compared between two groups. Results In recurrence group, U-RBC count and 24 h urinary protein level were gradually elevated and renal function steadily declined. Compared with non-recurrence group, U-RBC count at 2-, 3-and 5-year after renal transplantation significantly increased, and renal function was significantly aggravated at postoperative 5 years (all in P < 0.01-0.001) in recurrence group. Renal pathological findings revealed that compared with non-recurrence group, the incidence of cellular crescent formation, glomerulus adhesion, mesangial cell proliferation, increased mesentery matrix, glomerulosclerosis, segmental glomerulosclerosis, glomerular dysfunction and tubulointerstitial fibrosis was significantly higher in recurrence group (all in P < 0.001). After renal transplantation, chronic kidney injury index in recurrence group was 7.7±2.3, which was significantly higher than 4.6±1.4 in non-recurrence group (P < 0.01). Compared with non-recurrence group, the incidence of chronic rejection, glomerulopathy of transplant kidney(without IgAN) and positive C4d deposition was significantly higher in recurrence group (P < 0.01-0.001). At 1-and 3-year after renal transplantation, survival rates of transplant kidney did not significantly differ between recurrence and non-recurrence groups(93.8% vs. 86.7%, 95.6% vs. 88.3%, both in P>0.05). However, the survival rate at 5 years after transplantation was 51.4% in recurrence group, significantly lower compared with 83.8% in non-recurrence group (P < 0.001). In recurrence group, 10 patients (22%) presented with renal failure after renal transplantation, and 9 patients(9%) in non-recurrence group. Conclusions After renal transplantation, the recurrence of IgAN characterized by asymptomatic microscopic hematuria, albuminuria and progressive aggravation of renal function reduce long-term survival rate of renal graft and indicate poor prognosis.

Application of calcineurin inhibitor monotherapy in renal transplantation after alemtuzumab induction: a Meta-analysis

Xie Libo, Wang Yingqiang, Wang Xianding, Lin Tao, Lu Yiping

2016, 7(2): 100-105. doi: 10.3969/j.issn.1674-7445.2016.02.004

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Abstract:
Objective To evaluate the clinical efficacy and safety of immunosuppression of calcineurin inhibitor monotherapy (AiCNIm) after alemtuzumab induction following renal transplantation. Methods Randomized control clinical trials related to application of AiCNIm (AiCNIm group) and conventional triple regimes (Triple group) for immunosupression after renal transplantation, published from 1980 to December 31 2014, were searched online from PubMed, Embase, Web of Science, Cochrance library and China National Knowledge Infrastructure (CNKI)databases. Meta-analysis was performed by Rev Man 5.2 software. Results Five randomized control studies consisting of 421 renal transplant recipients were included. The results of follow up for 6-12 months revealed that compared with the Triple group, the incidence of rejection response confirmed by acute rejection or aspiration biopsy in the AiCNIm group was significantly lower [relative risk(RR)=0.59, 95% confidence interval (CI): 0.40-0.89]. However, there was no significant difference in the risk of renal allograft dysfunction (RR=0.85, 95%CI: 0.38-1.87), death of recipient (RR=0.89, 95%CI: 0.30-2.67), infection (RR=1.03, 95%CI: 0.91-1.17) and new-onset diabetes after transplantation(RR=0.62, 95%CI: 0.29-1.30) between two groups(all in P>0.05). Conclusions According to the existing evidence, application of calcineurin inhibitor monotherapy after renal transplantation exerts short-term immunosuppressive effect and high safety after alemtuzumab induction.

Diffuse alveolar hemorrhage syndrome after renal transplantation: one case report and literature review

Fan Yu, Qian Yeyong, Luo Yu, Bai Hongwei, Chang Jingyuan

2016, 7(2): 106-110. doi: 10.3969/j.issn.1674-7445.2016.02.005

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Abstract:
Objective To analyze and summarize clinical characteristics and treatment of diffuse alveolar hemorrhage syndrome(DAHS) complication after renal transplantation. Methods Clinical data of one patient, admitted to the 309^th Hospital of People's Liberation Army in December 2012, who was complicated with DAHS after renal transplantation, were obtained. The incidence, diagnosis and treatment courses of DAHS were retrospectively analyzed. Literature review was conducted to summarize clinical experience. Results The patient was clinically manifested with respiratory failure, progressive aggravation of hemoptysis and anemia. Imaging examination revealed that diffusive infiltration of bilateral lungs was aggravated. After the diagnosis of DAHS was confirmed, adrenal cortical hormone (hormone) shock and anti-infectious medication therapies were timely delivered to actively prevent and treat relevant complications. The patient was successfully healed. Until the submission date, the patient presented with normal renal function and no pulmonary complications were noted. Conclusions DAHS is a rare and fatal complication after renal transplantation. Early diagnosis, active anti-infection therapy and timely administration of large-dose hormone shock treatment determine the success of clinical treatment.

Clinical characteristics and analysis of rotavirus infection after liver transplantation in children

Wang Yongcui, Sun Liying, Zhu Zhijun, Wei Lin, Qu Wei, Liu Ying, Zeng Zhigui, He Enhui, Zhang Liang

2016, 7(2): 111-114. doi: 10.3969/j.issn.1674-7445.2016.02.006

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Abstract:
Objective To summarize the clinical characteristics and treatment of rotavirus infection after liver transplantation in children. Methods Thirty nine children undergoing liver transplantation in Beijing Friendship Hospital affiliated to Capital Medical University from October to December 2014 were retrospectively analyzed. And 6 cases were infected with rotavirus after liver transplantation. Characteristics of clinical symptoms, complications, treatments and prognosis in these six children were retrospectively analyzed. Results Six cases were diagnosed with rotavirus infection at 8-197 d after liver transplantation with a median time of 22 d, 3 cases of whom mainly manifested as high fever, diarrhea and vomiting and the remaining 3 presenting with diarrhea. The longer interval time between rotavirus infection and liver transplantation was, the slighter degree of rotavirus infection-related symptoms was. Among 6 cases, 5 cases were complicated with EB virus, cytomegalovirus or respiratory syncytial virus, and 2 cases were complicated with abnormal liver or heart function. The main treatment was decreasing the dose of FK506. Gamma globulin was administered in partial affected children to enhance immunity. Effective therapy was delivered to regulate intestinal tract bacterial colony and relieve diarrhea. All children recovered after oral use of antibiotics and supporting therapy using fluid infusion. Two cases complicated with severe cardiac and liver function abnormality were healed after expectant treatment. Conclusions Rotavirus infection-related symptoms are relatively severe after liver transplantation in children, occasionally complicated with cardiac and liver function injury, which can gradually return to normal after efficacious therapy.

Clinical study of effect on renal transplantation from donation of pediatric donors

Han Feng, Ding Chenguang, Tian Puxun, Xue Wujun, Ding Xiaoming, Pan Xiaoming, Yan Hang, Xiang Heli, Hou Jun, Feng Xinshun, Tian Xiaohui, Li Yang, Zheng Jin, Wang Xuzhen

2016, 7(2): 115-119. doi: 10.3969/j.issn.1674-7445.2016.02.007

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Abstract:
Objective To evaluate short-term clinical efficacy of renal transplantation from the donation of pediatric donors. Methods Clinical data of 15 pediatric donors and 28 recipients(including 2 cases of bilateral renal transplantation) undergoing renal transplantation in the Department of Renal Transplantation of the First Affiliated Hospital of Xi'an Jiaotong University from November 2013 to December 2015 were retrospectively analyzed. Results Renal transplantation was successfully performed in 28 recipients. The median warm ischemia time of transplant kidney was 12.5 min (range: 0-17.0 min) and 4.3 h (range: 1.5-7.7 h) for the median cold ischemia time. After operation, 4 cases developed with delayed graft function (DGF), 1 required dialysis, 2 died from pulmonary infection, 2 underwent renal resection due to renal anastomosis stenosis and renal thrombosis. Postoperative follow-up lasted for 1-24 months. Twenty-six (93%) recipients survived after renal transplantation and 24 (86%) recipients survived with restored normal renal function. Conclusions Unilateral and bilateral renal transplantation from pediatric donors has relatively favorable short-term clinical efficacy.

Application of ultrasound in extracorporeal membrane oxygenation for the liver donation after brain-cardiac death

Zhu Xiansheng, Cheng Qi, Wang Shasha, Ye Chuangwen, Pang Shuwang

2016, 7(2): 120-123. doi: 10.3969/j.issn.1674-7445.2016.02.008

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Abstract:
Objective To evaluate the application value of ultrasound in extracorporeal membrane oxygenation (ECMO) for protecting the liver donation after brain-cardiac death (DBCD). Methods Forty patients with brain death or irreversible brain injury, admitted to Guangzhou General Hospital of Guangzhou Military Command from April 2006 to November 2014, were eligible for liver donation. The hepatic artery blood flow (QHA), portal vein blood flow (QPV) and ECMO-induced ECMO flow of hepatic artery (VE) of the donor liver were monitored by ultrasound before, 5 min after the initiation of ECMO and immediately after ECMO. The changes of total bilirubin (TB), alanine transaminase (ALT) and lactic acid were observed at corresponding time points. Hepatic recovery was subsequently evaluated within 3 months after liver transplantation. Results The mean time of ECMO was (1.0±0.2) h. There was no significant difference in QHA and QPV before and after ECMO (both in P>0.05). And there was no significant difference in liver function parameters before and after ECMO (all in P>0.05). At different time points within postoperative 3 months, the results of ultrasound evaluation and liver function test revealed that the transplant liver function was well recovered in 40 recipients. Conclusions Through monitoring QHA by ultrasound, the best ECMO flow should be chosen, which protects DBCD liver and averts perfusion injury and hypoperfusion.

Clinical efficacy and safety of reduced-dose tacrolimus combined with increased-dose mycophenolate mofetil after renal transplantation

Pan Guozheng, Dai Shuai, Qiu Cheng, Liu Hongtao

2016, 7(2): 124-127. doi: 10.3969/j.issn.1674-7445.2016.02.009

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Abstract:
Objective To evaluate the clinical efficacy and safety of reduced-dose tacrolimus(FK506) in combination with increased-dose mycophenolate mofetil (MMF) after renal transplantation. Methods In this prospective study, 52 patients undergoing renal transplantation for over 12 months in the Department of Organ Transplantation, Anhui Provincial Hospital from January 2011 to January 2013 were recruited. All participants were randomly divided into the intervention group and control group(n=26 in each group). In the intervention group, blood trough concentration of FK506 was adjusted to 2.0-4.5 ng/ml and oral dose of MMF was adjusted to 1.5 g/d during 15 d after study. And in control group, blood trough concentration of FK506 was kept in 5.5-10.0 ng/ml and oral dose of MMF was 1.0 g/d constantly. The changes of the glomerular filtration rate (GFR) and serum creatinine (Scr) at 0 d, 15 d, and 2-, 4-, 6-, 8-, 10-, 12-month after corresponding treatment were statistically compared between two groups. At 1 year after therapy, triglyceride, total cholesterol and 24 h urinary protein levels were measured and compared between two groups. Moreover, the incidence of adverse reactions was also statistically compared. Results During the period from 0 d to 12 months after treatment, GFR did not significantly change in the control group (P > 0.05), whereas the value in the intervention group was considerably elevated (P < 0.05). The changes in terms of the GFR at 8-, 10-and 12-month after treatment significantly differed between two groups (all in P < 0.05). From 0 d to 12 months after therapy, the levels of Scr were significantly decreased in two groups (both in P < 0.05), and more apparent decline was noted in the intervention group. The changes in the Scr levels at 10 and 12 months after corresponding treatment significantly differed between two groups (both in P < 0.05). At 12 months after therapy, there was no significant difference in the levels of total cholesterol, triglyceride and mean 24 h urinary protein between the control and intervention groups (all in P > 0.05). No acute rejection or renal allograft dysfunction occurred in two groups. And there was no significant difference in the incidence of adverse reactions between the intervention and control groups (P > 0.05). Conclusions Combined therapy of reduced-dose FK506 and increased-dose MMF is an efficacious and safe immunosuppressive therapy.

Analysis of relationship between aldosterone level changes and renal function during perioperative period of renal transplantation

Fan Lianhui, Liu Long, He Long, Bi Xiaojun, Li Jian

2016, 7(2): 128-131. doi: 10.3969/j.issn.1674-7445.2016.02.010

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Abstract:
Objective To investigate the relationship between changes of aldosterone level and renal function during perioperative period of renal transplantation and preliminarily discuss the role of aldosterone in chronic allograft nephropathy. Methods One hundred patients undergoing allogeneic renal transplantation in the Department of Urology of the General Hospital of Shenyang Military from January 1, 2010 to December 31, 2013 were assigned into the experimental group. According to the Scr levels measured at 30 d after renal transplantation, 100 patients were divided into groups A (Scr≥133 μmol/L, n=13) and B (Scr < 133 μmol/L, n=87). Ten healthy individuals aged 25-35 years were recruited into the control group. In the experimental group, blood sample was collected in the morning upon the day of renal transplantation (0 d), 1, 7, 15 and 30 d after renal transplantation. In the control group, blood sample was obtained at the same time points for measurement of aldosterone and Scr levels. Results On the day of renal transplantation, the Scr level in the experimental group was (598±37) μmol/L, significantly higher compared with (75±5) μmol/L in the control group (P < 0.05). The aldosterone level in the experimental group was (0.26±0.06) ng/dl, considerably higher than (0.13±0.03) ng/dl in the control group (P < 0.05). Compared with 0 d, the Scr levels of group A significantly decreased at postoperative 30 d (P < 0.05), whereas no statistical significance was noted in aldosterone levels between two time points (P > 0.05). In group B, both Scr and aldosterone levels were significantly decreased at postoperative 30 d (both in P < 0.05). Correlation analysis revealed that the serum level of aldosterone was positively correlated with Scr level changes (r=0.85, P < 0.05). Conclusions After renal transplantation, change of Scr level is positively correlated with aldosterone level alterations, probably suggesting that aldosterone plays a partial role in mediating injury of transplant kidney during renal transplantation.

Experimental Researches

Effect of nodosin on accelerating hepatocyte regeneration after partial liver transplantation in rats

Zhou Xin, Ma Tiexiang, Li Feng, Liu Xiang, Zeng Jian, Li Shaojie, Liao Guoqing

2016, 7(2): 132-138. doi: 10.3969/j.issn.1674-7445.2016.02.011

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Abstract:
Objective To evaluate the effect of nodosin, as an effective element extracted from rabdosiae serrae, on hepatocyte regeneration after partial liver transplantation. Methods Wistar rats were used as donors and SD rats as recipients. Rat models with partial liver transplantation were established by modified two-cuff technique. Twenty-four recipient rats were randomly assigned into the nodosin and control groups. In the nodosin group, nodosin at a dosage of 100 μg/ml was administered via tail venous route after liver transplantation. Peripheral plasma and liver specimen were obtained at postoperative 3 and 7 d. The levels of alanine transaminase (ALT), aspartate aminotransferase (ALT) and albumin (ALB) in the peripheral plasma were measured by spectrophotometry. Hepatic histomorphological changes were observed under light microscope. The positive cell count of proliferating cell nuclear antigen (PCNA) antibody in the liver tissue was detected by immunohistochemistry. The expression levels of phosphorylated protein kinase (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), cyclin D1 and heme oxygenase (HO)-1 proteins were measured by western blot. The apoptosis of liver cells was detected by Annexin V method and TdT mediated-dUTP nick end labeling (TUNEL). Results Compared with the control group, the serum levels of ALT and AST were significantly lower at 3 d and 7 d after operation, whereas the ALB content was significantly higher in the nodosin group (all in P < 0.05). And nodosin could alleviate the pathological injury of rat liver tissue after transplantation. The positive cell count of PCNA in the nodosin group was significantly higher than that in the control group (P < 0.05). In the nodosin group, the expression levels of p-AKT, p-mTOR, cyclin D1and HO-1 proteins were significantly higher than those in the control group(all in P < 0.05). The quantity and percentage of apoptotic hepatocytes in the nodosin group were significantly lower than those in the control group (both in P < 0.05). Conclusions Application of nodosin can decrease the quantity of apoptotic hepatocytes and accelerate hepatocyte proliferation after liver transplantation in rat models.

Effect of pretreatment with allopurinol on the expression of Bax, Bcl-2 and Caspase-3 in kidney of ischemia-reperfusion injury rats

Chen Zhongbao, Zhou Jiangqiao, Qiu Tao, Ma Xiaoxiong, Chen Zhiyuan, Liu Xiuheng

2016, 7(2): 139-143. doi: 10.3969/j.issn.1674-7445.2016.02.012

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Abstract:
Objective To investigate the effect and mechanism of pretreatment with allopurinol on renal ischemia-reperfusion injury(IRI) in rats. Methods Twenty four rats were randomly assigned into the sham operation (S), ischemia-reperfusion (IR) and allopurinol pretreatment (APC) groups (n=8 for each group). At preoperative 2 weeks, allopurinol at a dose of 50 mg/(kg·d) was administered via intraperitoneal injection in the APC group, and an equivalent quantity of physiological saline was given via intraperitoneal injection in the S and IR groups. After pretreatment, the right kidneys of rats in the S group were resected. In the IR and APC groups, the right kidneys were resected and the left kidneys were treated with 30 min ischemia-reperfusion. Blood sample was collected at 24 h after reperfusion and the kidney specimen was obtained at postoperative 2 weeks. The levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were detected by automatic biochemistry analyzer. The activity of plasma malondialdehyde (MDA) and superoxide dismutase (SOD) was respectively assessed by detection kits. The expression levels of Bax, Bcl-2 and Caspase-3 of rat kidney were measured by western blot. Pathological changes in the rat kidney were observed under light microscope. Cell apoptosis of rat kidney was evaluated by TdT mediated-dUTP nick end labeling (TUNEL). Results Compared with the S group, the levels of BUN, Scr and plasma MDA in the IR and APC groups were significantly increased, whereas the activity of plasma SOD was significantly reduced(all in P < 0.05). Compared with the IR group, the levels of BUN, Scr and plasma MDA in the APC group were significantly reduced, whereas the activity of plasma SOD was considerably elevated (all in P < 0.05). Compared with the S group, the expression levels of Bax and Caspase-3 proteins were significantly up-regulated in the IR and APC groups, and the levels in the APC group were considerably lower than those in the IR group (all in P < 0.05). Compared with the S group, the expression of Bcl-2 in rat kidney in the IR and APC groups was significantly down-regulated, and the value in the APC group was dramatically higher than that in the IR group (all in P < 0.05). Under light microscope, the morphology of rat kidney was intact and normal in the S group. In the IR group, evident renal tubular ectasia, massive necrosis of renal tubular epithelial cells, evident stromal edema and a large quantity of lymph cellular infiltration were observed. In the APC group, mild renal tubular ectasia was observed, whereas no apparent kidney stromal edema was noted. A slight amount of lymph cellular infiltration was noted in the stroma. TUNEL staining revealed that the apoptosis rate of kidney cells in the S, IR and APC groups was (4.1±1.7)%, (32.8±8.9)% and (12.6±3.4)% (all in P < 0.05). Conclusions Allopurinol pretreatment could suppress cell apoptosis through anti-oxidation effect, thereby alleviating IRI of rat kidney and improving renal function.

Effect of thymoquinone on hepatic ischemic-reperfusion injury

Zhu Lei, Zhang Li

2016, 7(2): 144-149. doi: 10.3969/j.issn.1674-7445.2016.02.013

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Objective To investigate the effect and mechanism of thymoquinone on hepatic ischemia-reperfusion injury (IRI). Methods Thirty C57 mice were randomly divided into the sham operation (sham), IRI and thymoquinone (Thy) groups (n=10 in each group).At preoperative 1 h, thymoquinone at a dose of 40 ml/kg was administered via intraperitoneal injection in the Thy group. Absolute ethyl alcohol at the same dosage was given via intraperitoneal injection in the sham and IRI groups. Liver IRI mouse models were established in the IRI and Thy groups. Serum and liver specimens were collected at 4 h after reperfusion. Under light microscope, hepatic histopathological changes were observed and assessed by pathological injury grading. Reverse transcription polymerase chain reaction(RT-PCR) was performed to measure the messenger ribonucleic acid(mRNA) expression levels of tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1 and interleukin (IL)-6. The expression of TNF-α, MCP-1 and IL-6 proteins in the serum in the serum were assessed by ELISA. The content of malondialdehyde (MDA) in the liver tissue was detected by thiobarbituric acid (TBA). The activity of catalase (CAT), glutathioneperoxidase (GPx) and superoxide dismutase (SOD) in the liver tissue was determined by ELISA. The expression levels of Wnt, β-catenin and p53 proteins were measured by Western blot. Results Compared with the sham group, the liver injury was more severe and the hepatic injury grading was significantly enhanced in the IRI group (P < 0.05), the expression of TNF-α, MCP-1 and IL-6 in the liver tissue and serum sample, and MDA, Wnt, β-catenin and p53 in the liver tissue was significantly up-regulated (P < 0.05-0.001), whereas CAT, GPx and SOD activity in the liver tissue was dramatically reduced (all in P < 0.001). Compared with the IRI group, the liver injury in the Thy group was slighter and the liver injury grading was significantly decreased (both in P < 0.05). The expression levels of TNF-α, MCP-1 and IL-6 in the liver tissue and serum sample, MDA, Wnt, β-catenin and p53 in the liver tissue were significantly down-regulated (all in P < 0.05), whereas CAT, GPx and SOD activity was considerably up-regulated in the liver tissue (all in P < 0.05). Conclusions Thymoquinone can mitigate liver IRI through alleviating inflammatory response and oxidation stress. The underlying mechanism is correlated with inhibiting the activation of Wnt/β-catenin/p53 signaling pathway.