器官移植

Abstract:
Objective To investigate the relationship between immune tolerance and the changes of helper T cell (Th), regulatory T cell (Treg) cytokines, related signaling pathway proteins during immune tolerance process in rat models of liver transplantation. Methods The orthotopic liver transplantation rat models were established by double-cuff technique. All rats were divided into 3 groups. In the operative control group (n=6), sham operation was performed without liver transplantation. In the short-term group (n=10), the rats survived for 10 d after liver transplantation. In the immune tolerance group (n=10), the rats survived for 100 d after operation and the function of the transplanted liver was restored to normal. The expression levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), Th1 cytokines [interferon (IFN)-γ, interleukin (IL)-2 and tumor necrosis factor (TNF)-α], Th2 cytokines (IL-4, IL-5, IL-6 and IL-13), Th17 cytokines [granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-17A], Treg cytokines [IL-10, transforming growth factor (TGF)-β and IL-12p] were quantitatively measured. The serum sample of rats in each group was detected by protein chip analysis. Results Compared with the operative control group, the AST level in the short-term group was significantly down-regulated, whereas the ALT level was significantly up-regulated (both P < 0.05). However, the AST and ALT levels did not significantly differ between the immune tolerance group and operative control group (both P > 0.05). In the liver tissues of rats in each group, the expression levels of Th1 cytokines IFN-γ and IL-2 in the short-term group were significantly higher than those in the operative control group (both P < 0.05). The expression level of Th2 cytokine IL-4 in the immune tolerance group was significantly lower than that in the operative control group (P < 0.05). The expression levels of Th2 cytokines IL-5, IL-6 and IL-13 in the short-term group were significantly lower than those in the operative control group (all P < 0.05). The expression level of IL-17A in the immune tolerance group was significantly higher than that in the operative control group (P < 0.05). In the immune tolerance group, the expression levels of IL-10and IL-12p were significantly higher than those in the operative control group (both P < 0.05). The expression level of TGF-β in the short-term group was significantly higher than that in the operative control group (P < 0.05). Compared with the operative control group, the expression levels of intercellular adhesion molecule (ICAM)-1, pro-platelet basic protein (Ppbp), Neuropilin-2, Notch-2 protein in the short-term group were significantly up-regulated (all P < 0.05). The expression levels of CXC chemokine ligand 17 (CXCL17), ICAM-1 and Neuroleptin-2 protein were markedly up-regulated (all P < 0.05), whereas that of B7-1 protein was significantly down-regulated (P < 0.05) in the immune tolerance group. Conclusions Treg cytokines (IL-10, TGF-β and IL-12p), IL-6, IL-17 and trans-membrane signaling pathway molecules (ICAM-1, Neuropilin-2, B7-1 proteins) play a pivotal role in the natural immune tolerance process of rat models of liver transplantation.

Effect of protein kinase C β inhibitor on renal ischemia-reperfusion injury and expression level of macrophage subtypes in rat models

Fan Xuemei, Rong Song

2019, 10(4): 423-428. doi: 10.3969/j.issn.1674-7445.2019.04.012

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Abstract:
Objective To investigate the effect of protein kinase C (PKC) β inhibitor on the renal ischemia-reperfusion injury (RIRI) in rat models and detect the expression level of macrophage subtypes. Methods Eighteen healthy SD male rats were randomly divided into the Sham operation group (Sham group, n=6), RIRI group (n=6), PKCβ inhibitor +RIRI group (Inhibitor+RIRI group, n=6). Serum and left renal tissue samples were collected at postoperative 24 h. The contents of serum creatinine (Scr) and blood urea nitrogen (BUN) were detected by automatic biochemical analyzer. The infiltration of inflammatory cells and pathological injury in the renal tissues were observed by hematoxylin-eosin (HE) staining. The expression levels of CD68, inducible nitric oxide synthase (iNOS) and CD206 proteins in the renal tissues of rats in each group were assessed by immunohistochemistry and Western blot. Results The contents of serum Scr and BUN in the RIRI group were significantly higher than those in the Sham group (both P < 0.05). The contents of serum Scr and BUN in the Inhibitor+RIRI group were considerably lower than those in the RIRI group (both P < 0.05). No obvious renal injury was noted in the Sham group, whereas renal inflammatory cell infiltration and renal tubular structural damage were observed in the RIRI group. The renal inflammatory cell infiltration and renal tubular structural damage in the Inhibitor+RIRI group was slighter than that in the RIRI group. The protein expression levels of CD68, iNOS and CD206 in the renal tissue of rats in the RIRI group were significantly higher than those in the Sham group (all P < 0.05). The protein expression levels of CD68 and iNOS in the Inhibitor+RIRI group were remarkably lower than those in the RIRI group (all P < 0.05). The expression level of CD206 protein in the Inhibitor+RIRI group was significantly higher than that in the RIRI group (P < 0.05). Conclusions PKC β inhibitor can alleviate the RIRI in rat models to certain extent, which may be correlated with the role of PKC β inhibitor in mitigating inflammatory cell infiltration in ischemic renal tissues and promoting the expression of alternatively activated macrophage

Clinical Researches

Epidemiology of nosocomial infection in recipients after renal transplantation: a single-center analysis

Tan Yibin, Jin Xuelan, Li Yuan, Wu Songjie, Wang Ying, Tian Jia, Song Shihui, Wang Yanfeng

2019, 10(4): 429-433. doi: 10.3969/j.issn.1674-7445.2019.04.013

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Abstract:
Objective To investigate the epidemiological characteristics of renal transplantation recipients, effective prevention and control measures. Methods A total of 456 renal transplant recipients were monitored from January 2014 to December 2017. Postoperative infection including baseline data, infection site and infectious pathogen type was analyzed. Results Among 456 renal transplant recipients, 78 cases (17.1%) developed nosocomial infection. Postoperative infection time was 9(3-21) d. Infection sites mainly included the lower respiratory tract, urinary system and blood infection. Infection pathogens consisted of Staphylococci (n=13), Enterococcus faecium (n=6), fungi (n=6), Stenotrophomonas maltophilia (n=4), Acinetobacter baumannii (n=4), Pseudomonas aeruginosa (n=4), Staphylococcus epidermidis (n=4), Klebsiella pneumoniae (n=1), Escherichia coli (n=1) and other negative bacteria (n=9). Among them, 11 cases (14%) were infected with multi-drug resistant bacteria, and 4 cases died. Conclusions In renal transplant recipients, the incidence of nosocomial infection is relatively high, with early postoperative onset, common multiple drug-resistant bacterial infection and high mortality. Preoperative preparations should be fully implemented, postoperative lower respiratory tract infection should be actively prevented and prevention and treatment measures for multidrug-resistant bacteria should be standardized.

Clinical analysis of infection in recipients after renal transplantation

Long Chengmei, Yang Hua, Li Xinchang, Zhang Yu, Yang Jinran

2019, 10(4): 434-438. doi: 10.3969/j.issn.1674-7445.2019.04.014

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Abstract:
Objective To analyze the clinical characteristics of the recipients infected with cryptococcus neoformans after renal transplantation. Methods Clinical data of 9 patients infected with cryptococcus neoformans after renal transplantation were retrospectively analyzed, including the infection site, clinical manifestations, mycological, histopathological, imaging examination results, treatment process and clinical prognosis. Results Nine recipients were treated with routine triple immunosuppressive therapy of tacrolimus (FK506) + mycophenolate mofetil (MMF)+prednisone. The median time of onset was 6 years (1-13 years) after operation. Among them, 1 case was diagnosed with cryptococcal meningitis, 5 cases of cryptococcal meningitis complicated with cryptococcal pneumonia, 2 cases of cryptococcal pneumonia and 1 case of cutaneous cryptococcal infection. Cryptococcal pneumonia was clinically manifested as fever, cough, expectoration, shortness of breath and chest pain, etc. Chest CT demonstrated the signs of nodules and pleural effusion, etc. The diagnosis was mainly confirmed by lung biopsy and negative ink staining of the alveolar lavage fluid. Clinical manifestations of cryptococcal meningitis primarily included fever and paroxysmal headache accompanied by vomiting, which was mainly confirmed by blood culture and negative ink staining of the cerebrospinal fluid. Cutaneous cryptococcal infection was characterized by a mass in the right shoulder, which was confirmed by skin biopsy. All patients were given with standard antifungal therapy including amphotericin B and fluconazole, and immunosuppressive therapy at a reduced dosage. Among 9 recipients, 1 recipient died, and the other recipients obtained excellent clinical prognosis. Conclusions Cryptococcus neoformans infection dominantly occurs in the middle and late stage after renal transplantation presenting with non-specific clinical symptoms. Blood culture, lung biopsy and cerebrospinal fluid examination should be timely performed to validate the diagnosis of this disease. Standard anti-fungal therapy can reduce the mortality rate.

Clinical study of value of serum Klotho level of elderly donors in predicting postoperative renal graft function in recipients

Wang Jianfu, Deng Gengguo, Zhu Chunli, Li Qin, Zhou Jiexue, Meng Shandong, Shen Sheng, Wang Xiao, Ma Juan, Liu Dong

2019, 10(4): 439-442. doi: 10.3969/j.issn.1674-7445.2019.04.015

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Abstract:
Objective To explore the feasibility of serum Klotho level in the elderly donors to predict the renal graft function in the recipients. Methods Clinical data of 16 elderly donors and 27 recipients undergoing renal transplantation were collected. The general status of the recipients was observed. The levels of serum Klotho and serum creatinine (Scr) in the elderly donors were measured on the day of renal transplantation. The Scr levels in the recipients were measured at postoperative 1, 3 and 12 months respectively. The estimated glomerular filtration rate (eGFR) was calculated. The correlation between the serum Klotho level of the donors and postoperative graft function of the recipients was analyzed. Results The cold ischemia time during renal transplantation was (649±245) min. The incidence rate of delayed graft function (DGF) was 26%. The incidence rate of acute rejection was 7%. In the elderly donors, the serum Klotho level was 537 (245-793) pg/mL and the Scr level was (164±62) μmol/L. At postoperative 1, 3 and 12 months, the Scr levels in the recipients were (136±47), (132±43) and (133±46) μmol/L, respectively. The corresponding eGFR was (52±20), (52±19) and (53±21) mL/(min?1.73m²), respectively. The serum Klotho level in the elderly donors was negatively correlated with the renal graft function at postoperative 1 month in the recipients (P < 0.05). The sensitivity and specificity of serum Klotho level in predicting the renal graft insufficiency at postoperative 1 month were 0.909 and 0.769. Conclusions The preoperative serum Klotho level in the elderly donors have predictive value for renal graft function in the recipients at postoperative 1 month.

Individualized treatment of splenorenal shunt during liver transplantation

Cheng Daorou, Yang Qing, Zhang Yingcai, Wang Li, Chen Xiaolong, Li Hui, Yang Yang, Chen Guihua, Wang Genshu

2019, 10(4): 443-448. doi: 10.3969/j.issn.1674-7445.2019.04.016

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Abstract:
Objective To evaluate the safety and efficacy of individualized treatment of splenorenal shunt during liver transplantation. Methods Clinical data of 2 recipients who underwent orthotopic liver transplantation and splenorenal shunt intraoperatively were retrospectively analyzed. According to the perfusion status after splenorenal shunt and donor liver reflow, the left renal vein ligation and splenorenal shunt vessel ligation were performed in two recipients during liver transplantation. The general postoperative conditions of the recipients were observed, including surgical related complications, peak portal blood flow velocity, liver and renal function indexs. The postoperative conditions of the recipients were monitored by abdominal ultrasound. Results No intraoperative or postoperative complications occurred in two recipients. The changes of peak portal blood flow velocity before and after splenorenal shunt in two recipients were 22.9-35.1 cm/s and 24.3-58.8 cm/s respectively. No delayed recovery of alanine aminotransferase (ALT) level was observed in two patients after operation. Case 1 experienced a transient increase in the serum creatinine (Scr), which was recovered to normal at postoperative 13 d. During the postoperative follow-up, ultrasound examination demonstrated that the direction and velocity of portal blood flow were normal and liver perfusion was excellent. Conclusions It is safe and effective to selectively ligate the left renal vein or splenorenal shunt vessels of the recipients with severe splenorenal shunt during liver transplantation.

Therapeutic experience of tacrolimus-induced pain syndrome of bilateral lower limbs after liver transplantation

Zheng Yonggen, Zhou Lin, Du Guosheng, Zhu Zhidong, Feng Likui

2019, 10(4): 449-452. doi: 10.3969/j.issn.1674-7445.2019.04.017

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Abstract:
Objective To summarize the therapeutic experience of lower limb pain syndrome caused by tacrolimus (FK506) after liver transplantation. Methods A 52-year-old male patient diagnosed with virus B hepatitis (hepatitis B), post-hepatitis liver cirrhosis at the decompensation stage and malignant liver tumors developed bilateral lower limbs pain syndrome after liver transplantation with FK506 immunosuppressant. After eliminating the possibility of angioneurotic pain, FK506 was terminated and replaced by sirolimus (SRL) therapy. The blood concentration was maintained at 6~8 ng/mLduring the early stage, and then gradually adjusted according to the survival time of the liver graft. Results After 2-weeks conversion therapy, the swelling and pain of bilateral lower limbs of the patient were gradually relieved, and the skin pruritus was gradually healed. After 1 month, the patient was basically restored to normal activity and function. No recurrence was reported until the submission date of this manuscript. Conclusions Bilateral lower limbs pain syndrome caused by adverse reaction of FK506 is relatively rare. FK506 can be substituted by SRL to avoid the adverse reaction.