Internal audit of Organ Procurement Organization under the requirements of high-quality development / 器官移植

High-quality development is the primary task of building a socialist modern country in an all-round way. Organ donation and transplantation in China are evolving from high-speed growth to high-quality development, which put forward new requirements for the safe, stable and healthy operation of Organ Procurement Organization (OPO). Safety is the foundation and prerequisite for achieving the goal of high-quality development. As an independent and comprehensive department, internal audit should create new achievements in the new era. The department should include OPO and organ donation into the scope of internal audit, shift the emphasis upon the overall development of organ donation. Besides, it should fully consider the actual situation in different places, conduct all-round, objective and fair evaluation, provide evaluation and consulting services for OPO to properly implement organ donation, and give full play to the supervision and prevention role of internal audit.

Discussion on the establishment of the discipline of "organ donation" / 器官移植

Vivid and abundant social practice constantly creates new understanding, which will inevitably lead to the emergence of new disciplines. Organ donation discipline is involved with multiple disciplines, such as ethics, law, medicine, sociology and psychology, etc. After entering a new stage of high-quality development, whether it is necessary to establish the discipline of "organ donation" is worthy of discussion. According to the basic standards for establishing a new discipline, groundbreaking achievements in organ donation could lay a solid foundation for the establishment of "organ donation" discipline. However, current conditions for the establishment of "organ donation" are not fully mature, and the process of discipline establishment will absolutely encounter resistance. In the future, the scope and orientation of organ donation should be further elucidated, and a series of measures should be taken, such as establishing independent academic organizations, offering organ donation courses, carrying out special research and innovation, and strengthening international cooperation and exchanges, aiming to promote the establishment of organ donation discipline. The cooperation between academic community and governments is the key to promote the establishment of the discipline of organ donation. Governments will make final decisions by comprehensively considering the investment of resources, development needs of the discipline and the relationship among existing disciplines.

Current status analysis and development strategy of united Organ Procurement Organization / 器官移植

With the reform of organ donation and transplantation in China, the establishment of Organ Procurement Organization (OPO) will become more centralized and enlarged in scale, evolving into the united OPO development stage coordinated by multiple hospitals. How to enhance the operation management and scientific development planning of united OPO has become an urgent and novel issue facing the administrators at all levels. At present, certain constraint factors of united OPO still exist in the integrated management, cost control, service homogenization, cultural integration and discipline layout. To give full play to the large-scale benefits and expand the supply of high-quality organ donation services, the development principle of putting connotation construction first and the appropriate direction of public welfare should be upheld. Leading and driving the development of organ donation services of our province are the responsibility, and discipline construction and talent training serve as the core. The overall development plan should be determined in a scientific pattern and homogeneous management should be implemented according to local conditions, aiming to provide successful experience for establishing a provincial unified OPO.

Establishment and management of clinical use price of donation after citizen's death based on cost accounting / 器官移植

In recent years, the fields of donation after citizen's death and organ transplantation in China have developed rapidly with remarkable achievements and revolutionary changes in the source of transplant organs.How to transform the development of organ donation and transplantation from high-speed to high-quality growth mode?It is extremely urgent to establish the expenditure and management system of organ donation and transplantation.In this article, the establishment and management of clinical use price of organs from donation after citizen's death were investigated from the perspectives of policy basis, accounting items, accounting methods, price formation and price management, aiming to provide reference for resolving the problem of cost accounting and price determination of clinical use of donated organs.

Establishment of quality management system of Organ Procurement Organization with Chinese characteristics / 器官移植

Quality assurance is the responsibility of Organ Procurement Organization (OPO). The establishment of OPO quality management system is a novel task for implementing high-quality human organ donation. At present, the quality management of OPO still has certain problems, such as lack of comprehensive management organization, standardized management process, scientific evaluation index, qualified professionals and strong safety culture atmosphere, etc. It is necessary to deliver top-level design from three perspectives of ideological concept change, quality management system construction and process implementation management in combination with the actual situation of OPO and reference to the criteria of international general quality management system. More importantly, the managers of OPO should play a leading role in ensuring the efficient operation of OPO in the persistent improvement of quality management system.

Differential gene expression profile of miRNAs in mouse models with renal ischemia-reperfusion injury / 器官移植

To screen the differentially-expressed microRNAs (miRNAs) in mouse models with renal ischemia-reperfusion injury (IRI),aiming to offer foundation for unraveling the molecular mechanism of the incidence and progression of IRI.Methods The mouse models with acute IRI were established by renal artery clamping.Fifteen mice were divided into the IRI group and sham surgery group (E group).The animals in the IRI group were subdivided into the A group (45 min ischemia followed by 24 h reperfusion),B group (25 min ischemia followed by 24 h reperfusion),C group (45 min ischemia followed by 4 h reperfusion) and D group (25 min ischemia followed by 4 h reperfusion) (n=3 for each group).The severity ofIRI was evaluated by histological changes and renal function.The differentially-expressed miRNAs in the IRI mouse models at different ischemia time (25 and 45 min) and reperfusion time (4 and 24 h) were screened by using cluster analysis of miRNAs microarray data.The differential expression of miR-695 and miR-145 was validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR).Results Both histological changes and renal function confirmed that the IRI mouse models were successfully established.Compared with the sham surgery group,71 differentially-expressed miRNAs were detected in the IRI group including 30 down-regulated miRNAs and 40 up-regulated miRNAs.The results of qRT-PCR demonstrated that if the standardized expression level of miRNAs in the E group was 1,the relative expression levels of miR-695 and miR-145 were 11.82 and 0.31 in the IRI group (both P＜0.05),which were consistent with the chip results.Conclusions After renal IRI,different changes occur in the gene expression profile of miRNAs.These differentially-expressed miRNAs act as molecular biomarkers for renal IRI with potential clinical and scientific research values.

Anemia in patients after renal transplantation:Five-year follow-up in 154 cases / 中国组织工程研究

BACKGROUND:Recent studies have shown that anemia after renal transplantation is an important risk factor for cardiovascular disease after transplantation, as wel as the independent predictor of death. OBJECTIVE:To explore the prevalence, processing and risk factors of anemia after renal transplantation. METHODS:The data of 154 cases renal transplantation recipients who fol owed-up in the Department of Urology, Fuzhou General Hospital of Nanjing Military Command were retrospectively analyzed. The blood routine and blood biochemistry of the renal transplantation patients were col ected for analysis during hospitalization and 1, 2, 3, 4 and 5 years after transplantation. RESULTS AND CONCLUSION:The prevalence of anemia during transplantation and the subsequent 5 years after transplantation were 45.5%, 10.7%, 9.6%, 14.8%, 13.5%and 19.6%, respectively. Patients had anemia at least once in five years, and 42%of the patients experienced recurrence. Relative analysis showed that hemoglobin levels were associated with function of transplanted kidney. Different genders, ages and the using of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers or not has no correlation with the prevalence of anemia. Binary Logistic regression analysis showed that serum creatinine and blood urea nitrogen levels at 1 year after transplantation were correlated with the diagnosis of anemia, and only associated with serum creatinine level at 5 years after transplantation. Iron drug is relatively common, but erythropoietin is rarely applied in the anemia patients with transplant renal insufficiency. The prevalence of anemia after renal transplantation is high, and transplant renal insufficiency is a major risk factor for the disease.

Measurement of cell-mediated immune function in elderly renal allograft recipients by ImmuknowTM assay / 中华器官移植杂志

Objective To evaluate the values of cell-mediated immune function in elderly renal allograft recipients.Method The levels of immuknowTM ATP was sequentially monitored by means of Cylex immuknowTM assay in 52 elderly renal allograft recipients including 11 with infection and 8 with acute rejection.Results No statistically significant difference was found between stable allograt function and uremia (P＞0.05).The levels of immuknowTM ATP during infection was significantly lower than those with stable allograft function with acute rejection (P ＜ 0.01).The levels of immuknowTM ATP during acute rejection was significantly higher than those with stable allograft function with infection (P＜0.01).Conclusion Sequential monitoring of immuknowTM ATP is helpful for elderly renal allograft recipients in individualized immunosuppression therapy.Cylex immuknowTM assay can be used as a potent tool for assessment of high risk in infection and rejection.

Y-type partial duplication of a vaginal ectopic ureter with ipsilateral hypoplastic pelvic kidney and bicornuate uterus

We present a case of vaginal ectopic ureter with ipsilateral partial duplication of the upper ureter (Y-type ureter), ipsilateral hypoplastic pelvic kidney and bicornuate uterus in a 20-year-old woman who presented with mild urinary incontinence since infancy. Ultrasonography, computed tomography and intravenous pyelography examination showed a left kidney with no evidence of a right kidney. Cystourethroscopy showed absence of the right hemitrigone. Magnetic resonance (MR) urography demonstrated the presence of a bicornuate uterus, an ectopic dysplastic right kidney in the pelvic cavity, and a right ureter that terminates in the vaginae fornix. The patient underwent right nephroureterectomy and urinary continence was restored completely. Although congenital malformations of the urinary tract are frequently associated with genital tract abnormalities, to best our knowledge, this is the first report of the coexistence of all of these anomalies in an individual. Our report also highlights the importance of MR urography in the diagnosis of such rare and complex anomalies.

Effect of CYP3A4*18B, CYP3A5*3 gene polymorphism on dosage and concentration of tacrolimus in renal transplant patients / 药学学报

The effect of CYP3A4*18B and CYP3A5*3 on concentration/dosage x body surface area ratios (C/D'), adverse effects and acute rejection of tacrolimus in renal transplant patients were investigated. The CYP3A4*18B genotypes of 227 renal transplant patients were determined by PCR-RFLP method. The differences of C/D' ratios, adverse reactions and acute rejection were compared among all of the genotype groups treated with tacrolimus. The frequencies of CYP3A4*18 and CYP3A5*3 alleles in renal transplant patients were 30.8% and 74.2%, respectively. No significant association was found between the C/D's of tacrolimus and CYP3A4*18B genotypes when they were classified by two CYP3A5 genotypes (P > 0.05). While after the effects of CYP3A4*18B genotype were eliminated, the C/D' ratio of tacrolimus in patients with CYP3A5*1/*1 and *1/*3 genotype group was significantly lower than those with CYP3A5*3/*3 genotype groups (P 0.05).

Clinical outcomes in renal allograft recipients switched to long-term immunosuppressive therapy with mycophenolate mofetil after renal transplantation / 中华器官移植杂志

Objective To document the impact of conversion to mycophenolate mofetil (MMF)at different time points after transplantation on the renal function of renal function.Methods A longterm,multicenter,non-interventional and observational study was done.Two cohorts were included:One was Switch cohort (340 cases) including renal allograft recipients who switched to MMF at least 6 months after renal transplantation and followed up for 4 years after switch; The other was Stay cohort (123 cases),including renal allograft recipients who received MMF treatment after transplantation and followed up for 4 years after enrollment.Results GFR values of patients in Switch cohort was significantly increased after switch,and the change in GFR slope was 3.1 mL· min-1 · year-1 (P＜0.01).GFR values of patients in Stay cohort kept steady before and after enrollment,and the change in GFR slope was 0.44 mL·min-1 ·year-1 (P＞0.05).Statistically significant difference in the onset time of GFR decline (defined as 20％ decline from the baseline) was observed among subgroups within Switch cohort (P＜0.01),but there was no significant difference among subgroups within Stay cohort (P＞0.05).Stay cohort was 12％ higher than in Switch cohort every year.Conclusion Conversion to MMF ＞6 months or even many years after transplantation can obviously improve the renal function of recipients.The earlier conversion can benefit improvement of the renal function.

Efficacy of the program of rapamycin combined with CNI in chronic allograft nephropathy / 中华器官移植杂志

ObjectiveTo investigate the efficacy of rapamycin combined with CsA/Tacrolimus (Tac) in chronic allograft nephropathy (CAN).MethodsFifty-three cases of CAN accepted the quadruple immunosuppressive drug program,which contained rapamycin combined with CsA/Tac and MMF and prednisone,and CsA/Tac and MMF were reduced to the original amount of 25％ to 50％.After treatment for 12 months,more relevant indicators,including serum creatinine,glomerular filtration rate,serum cholesterol,triglycerides,urinary protein,GPT and bilirubin and other changes were observed.ResultsIn the patients receiving quadruple regimen of rapamycin during 12 months,the blood Ccr was decreased from (161.51 ± 106.48)μmol/L before treatment to (126.51 ± 56.2)μmol/L after treatment for 6 months (P＜0.05) and to (123.43 ± 54.18)μmol/L after for 12 months (P＜0.01).The GFR was increased from (0.754 ± 0.302) ml/s before treatment to (0.952 ± 0.347)ml/s after treatment for 6 months (P＜0.05) and to (1.007 ± 0.394) ml/s after treatment for 12 months (P＜0.01).Cholesterol and triglycerides in patients had no significant change before and after treatment.The positive rate of proteinuria after treatment showed an increasing trend from 9.4％ before treatment to 26.4％ after treatment for 12 months.ConclusionThe quadruple program of rapamycin combined with CsA/FK506 and MMF can significantly improve Ccr and GFR in patients with CAN,but it can increase the incidence of proteinuria in patients:

Comparative proteomic analysis of renal tubular epithelial cell injury caused by oxalic acid and calcium oxalate monohydrate / 中华泌尿外科杂志

Objective To analyze and identify the differentially expressed proteins in human renal tubular epithelial cells (HK-2) after injury caused by oxalic acid and calcium oxalate monohydrate (COM) crystal, and to explore the potential role of renal tubular cell injury in kidney stone formation.Methods Normal HK-2 cells were cultured in vitro and the culture medium was changed with serum-free medium after cell growth to confluence. Oxalic acid and COM crystals (final concentration at 2 mmol/L and 200 mg/L, respectively) were added in the experimental group. Cells in both groups were then incubated at 37 ℃ for 12 h. The extracted proteins from both groups were separated by two dimensional electrophoresis followed by analysis, and the differentially expressed proteins were identified by liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Two identified proteins were then verified by western blot. Results Reproducible two dimensional gel images of the proteins from both groups were successfully obtained. By using LC-ESI-MS/MS, 12 proteins: FK506-binding protein 4, isoform alpha-enolase of alpha-enolase, isoform M1 of pyruvate kinase isozymes M1/M2, ATP synthase subunit alpha, isoform 1 of 3′(2′), 5′-bisphosphate nucleotidase 1, isoform 2 of nucleophosmin, L-lactate dehydrogenase B chain, Budding uninhibited by benzimidazoles 3, Cofilin-1, Fascin, pyIsoform 1 of cytosol aminopeptidase, were identified. The deferentially expressed proteins were related to cellular processes including energy metabolism, cell multiplication, apoptosis, Ca2+ channel activity regulation, cell movement and signal transduction. Western blot verified that higher ENO1 but lower Cofilin-1 expressed in HK-2 cells after the injury. Conclusions High level oxalic acid and COM crystals can cause protein expression profile changes in normal human HK-2 cells. The changes of protein expression may not only protect HK-2 cells from being injured, but also be related to kidney stone formation.

The efficacy and safety of induction therapy with autogenous mesenchymal stem cells perfusion before operation in cadaveric kidney transplantation / 中华器官移植杂志

Objective To evaluate the efficacy and safety of mesenchymal stem cells(MSCs)in preventing early acute rejection after renal transplantation.Methods Eighty-eight primary cadaveric renal allograft recipients in our department were randomized into two groups treated with bone marrow MSCs (BMSCs group,n =43) or not (control group,n =45).Main immunosuppressive therapy regimen consisted of steroids,tacrolimus or cyclosporine and mycophenolate mofetil in all recipients.Estimated glomerular filtration rate (eGFR) of transplant kidney,incidence of acute reaction (AR),graft survival and incidence of adverse events were recorded within 24 months.Results In BMSCs group,the incidence of AR was 4.7 ％ and 9.3 ％ at 3rd month and 6th month respectively,significantly lower than 20.0 ％ and 26.7 ％ (P＜0.05) in the control group.The eGFR at day 7,14and 30 post-transplantation was significantly higher in the BMSCs group than in the control group (P＜0.01,P＜0.01,P＜0.05 respectively).The incidence of adverse events in the BMSCs group and the control group was 44.2 ％ (19/43) and 66.7 ％ (30/45,P ＜ 0.05) respectively and the rate of infection was 37.2 ％ (16/43) and 33.3 ％ ( 15/46,P ＞ 0.05) respectively within 24 months.Conclusion Induction therapy with autogenous BMSCs appeared to be more effective in the prevention of AR following cadaveric kidney transplantation and was associated with better clinical outcomes as far as early renal graft function without compromising patient safety.

Application of single antigen antibody test in living-relative renal transplantation / 中华器官移植杂志

Objective To analyze the clinical application of donor specific antibodies (DSAs) detected by a single antigen Luminex virtual crossmatch,and to discuss the treatment of DSA and the impact of DSA on renal function.Methods Serum from living-relative renal recipients before and after transplantation was investigated using a Luminex single antigen assay.The relation between DSA and renal acute rejection as well as renal function was analyzed.Results A total of 30 patients and 173 serum samples were tested,including 47 serum samples before transplantation,and 126 after transplantation.DSA was positive in one patient before transplantation,and 8 patients after transplantation.Three of the patients positive for DSA were treated by Bortezomib,3 by addition of MMF,2 by addition of CNI,1 by addition of Sirolimus.The MFI of DSA in one of the patients treated by Bortezomib was decreased to below 1000,while that in the other two decreased by more than 50 ％.The renal eGFR at the time with and without DSA was (1.50 ± 0.59) and (1.23 ± 0.38)ml/s respectively (P＜0.05).Conclusion Dynamic monitoring of single bead antigen antibody DSA conduces to direct the adjustment of immunosuppressant.The appearance of DSA contributes to the declination of renal function.Application of Bortezomib decreased the MFI of DSA.

Clinical implication of complement split product C4d in patients with antibody-mediated chronic rejection / 中华器官移植杂志

Objective To explore the significance of peritubular capillary C4d deposition in histopathological changes, renal function and prognosis of the patients with antibody-mediated chronic rejection (AMCR). Methods Deposition of C4d in the kidney was examined by irnmunohistochemistry on routine paraffin-embedded sections using anti-C4d polyclonal antibody. Seventy-seven patients were divided into C4d+ group (n = 35) and C4d- group (n = 42). The relationship of C4d and renal function,histopathological changes and prognoses of allografts were analyzed. Results The number of patients with tubular atrophy and glomerular basement membrane proliferation in C4d+ group was significantly more than that in C4d group (P＜0.05). Mean serum creatinine level was significantly higher in C4d+ group than in C4d- group 12 months after renal transplantation [(379.1 + 260.2)μmol/L vs (260.5 + 175.3) μmol/L, P＜0.05]. According to Kaplan-Meier analysis, the one-year graft survival rate was lower in the C4d+ group (62.9% ) than in the C4d- group (83.3% ) (logrank P＜0.05). Conclusion Patients with C4d deposition are associated with tubular atrophy and glomerular basement membrane proliferation. The serum creatinine level in C4d+ patients was significantly higher than in C4d- group at the 12th month after transplantation. More patients with C4d deposition lost their grafts during the study period.

Efficacy and safety of Alemtuzumab induction in kidney transplantation / 中华器官移植杂志

Objective To evaluate the efficacy and safety of alemtuzumab in renal transplant recipients treated with induction therapy. Methods Eighty-nine cadaveric renal transplant recipients in our department were randomly divided into experimental group (n = 43) treated with alemtuzumab induction, 15 mg i. v. and control group (n = 46). Main immunosuppressive therapy regimen consisted of steroids, tacrolimus or cyclosporine and mycophenolate mofetil in all recipients. Post-transplant kidney function, acute rejection,infection, DGF, graft survival, lymphocyte counts were recorded within 1 year. ATP values in CD4+ T cells after transplantation was determined by using Cylex ImmuKnow assay. Results There was significant difference in the incidence of biopsy-proven acute rejection, but no significant difference was found in ImmuKnow ATP values during 6 months after transplantation and lymphocyte counts during 3 months, graft survival and the incidence of infections between the two groups. Conclusion Induction therapy with alemtuzumab appeared to be effective in the prevention of acute rejection.

Diagnosis and treatment of urinary fistula following kidney transplantation / 中国组织工程研究

BACKGROUND: Presently, the kidney source is limited. Urinary fistula-induced nephrectomy of transplanted kidney is regrettable. Reasonable diagnosis of urinary fistula should be paid great attention by workers of organ transplantation. OBJECTIVE: To study the diagnosis and treatment of the urinary fistula in kidney transplantation patients. METHODS: The clinical data of 16 patients with the urinary fistula following kidney transplantation, who was recruited from the Organ Transplantation Center, Fuzhou General Hospital of Nanjing Military Area Command of Chinese PLA, were retrospectively analyzed. RESULTS AND CONCLUSION: The morbidity of the urinary fistula following kidney transplantation was 1.26%, the conservative treatment were used to 13 cases of simple urinary fistulas, 11 of 13 cases were successful (84.6%). 2 case failed (15.4%), pedicled omentum grafts were successful used to treat 3 cases of complex urinary fistulas after renal transplantation by one operation. Intensive care and active measures should be given to the urinary fistula patients after kidney transplantation. The key to the successful treatment involved with the diagnosis in early stage and the correct measures. With biological characteristics of omentum, applying pedicled omentum grafts to repair complex urinary fistulas and simple urinary fistulas which were failure of the conservative treatment after renal transplantation has advantages as followings, convenient to draw material, recovering tissue quickly and low recurrence rate. It is fit for clinic.

Construction and identification of eukaryotic expression vector of rat Delta1 gene / 中国组织工程研究

BACKGROUND: Recent data suggested that Notch signal pathway plays important regulatory effects in peripheral transplantation immunological response, promotes differentiation of regulatory T cells, induces antigen specific immune tolerance. We proposed that Notch/Notch ligand may play important roles in MHC/TCR interface.OBJECTIVE: To construct the eukaryotic expression vector of rat Deltai gene (Notch ligand), and to examine its expression in dendritic cells.METHODS: The complete encoding cDNA of rat-Delta1 was isolated from bone marrow cells by reverse transcription-polymerase chain reaction (RT-PCR) and this gene was recombined into pcDNA3.1(+) plasmid vector.pcDNA3.1/Delta1 plasmid was transfected into rat dendritic cells with lipofectamine gene transfection method.RESULTS AND CONCLUSION: Double enzyme digestion detection demonstrated that Delta 1 had been successfully constructed in Hindilll and xbal of pcDNA3.1. A positive clone pcDNA3.1/Delta1 was delivered to Shanghai Sangon Biological Engineering Technology & Services Co., Ltd. for sequencing. Sequencing results were identical to Delta1 gene sequence in Genebank, with correct reading frame. The Delta 1 gene-transfected dendritic cells showed similar morphology as their parent cells. Western blotting assay detected that Delta 1 expression was significantly increased in cells. The eukaryotic expression vector pcDNA3.1/Delta1 was constructed, and significant increase of Delta 1 expression was detected after transfection.

Time-zero renal biopsy: Correlation analysis of clinical predonation parameters and histological abnormalities / 中国组织工程研究

BACKGROUND: The number of living renal donation has increased in China and abroad, thus, it is important to guarantee the safety of donors. How to accurately diagnose potential renal disease and provide guidance plays an import role in protecting safety of living renal donors.OBJECTIVE: To establish an evaluation method for analyzing the correlation between histological abnormalities and clinical predonation parameters.METHODS: The related data on renal transplantation of Fuzhou general Hospital of Nanjing Military Area Command of Chinese PLA were retrospectively reviewed. Paracentesis were performed when the vessels of kidney were mutilated and perfusions were finished. Time-zero renal biopsy was evaluated for following pathological changes: interstitial fibrosis, tubularatrophy, arteriolar hyalinosis, mesangial proliferation, and glomerulosclerosis. Predonation data were demography, body weight, body mass index' systolic/diastolic blood pressure, serum creatinine, glomerular filtration rate, and proteinuria.RESULTS AND CONCLUSION: There were no signs of kidney disease in preoperative examination of all the 62 patients, time-zero renal biopsy found there were 28 donors with histological changes, interstitial fibrosis with age and serum creatinine, tubularatrophy with diastolic blood pressure and protein excretion rate, arteriolar hyalinosis with serum creatinine and glomerular filtration rate, mesangial proliferation only with body mass index, and finally the presence of glomerulosclerosis did not correlate with any variable.