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Objective To investigate the effect of CYP3A5 and MDR1 gene polymorphisms on blood concentration of tacrolimus and creatinine level in uremic patients during the early phase after kidney transplantation in real clinical practice. Methods 131 patients who underwent kidney transplantation for the first time with triple immunotherapy based on tacrolimus in single-center from 2013 to 2017 were enrolled for retrospective study. Tacrolimus daily dose, blood concentration, blood concentration-to-dose ratio, and serum level were compared according to the various genotypes of CYP3A5 and MDR1 polymorphisms in renal transplantation recipients, respectively. Results The dosage of tacrolimus in CYP3A5*3/*3 (GG) kidney transplantation recipients within 4 weeks after kidney transplantation was lower than those of CYP3A5*1/*1 (AA) and CYP3A5*1/*3 (AG). The serum creatinine levels of patients whose tacrolimus concentration in the range of 10-13 ng/ml were close to the normal value. Conclusion CYP3A5 gene polymorphism affects the blood concentrations of tacrolimus in renal transplant recipients. No association has been found between the blood concentrations of tacrolimus and MDR1 gene polymorphism. Tacrolimus concentration in the range of 10-13 ng/ml might contribute to restore the early kidney graft function.
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Objective:To explore the causes, clinical characteristics, diagnoses and outcomes of post-lymphoproliferative disease(PTLD)after renal transplantation.Methods:Retrospective reviews were conducted for a total of 2 844 adult kidney recipients between January 2000 and January 2019. And 13 of them developed PTLD. Their clinical features and outcomes were analyzed. There were 11 males and 2 females with a median age of 55(31~78)years. All were diagnosed as diffuse large B-cell lymphoma at a median time of 86(12~204)months post-transplantation.Results:The locations of PTLD were diverse, including lung, stomach, colon, skin and central nervous system. Biopsy immunohistochemical EBV positivity was detected in 76.9% of cases.After a tapering of immunosuppression intensity, 6 cases were operated. Patients not tolerating R-CHOP regimen (rituximab + CHOP) were switched to R2 regimen(rituximab + nalidomide). The total effective rate was 91.6%, including complete remission(10 cases), partial remission(1 cases), progressive disease (1 case)and death(2 cases).Conclusions:As a rare but serious complication after renal transplantation, PTLD is closely correlated with EBV infection.Reducing the dose of immunosuppressive drugs is a core of comprehensive treatment.Switching to R2 regimen is an effective alternative in the treatment of PTLD after renal transplantation.
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Objective:To explore the clinical characteristics, diagnosis and treatment of cryptococcal infection after renal transplantation.Methods:The clinical data were analyzed retrospectively for 17 hospitalized cases of cryptococcal infection after kidney transplantation from January 2003 to December 2019. The relevant parameters included site of infection, clinical manifestations, complications, comorbidities, treatments and outcomes. The average time to infection after transplantation was (7.9±5.4) years, the median baseline level of creatinine was 137(75-741) μmol/L. Concurrent conditions included hypertension (n=15, 88.2%), diabetes (n=6, 35.3%) and chronic hepatitis (n=9, 52.9%). The most common site of infection was central nervous system (88.2%), followed by lungs (29.4%) and skin (17.6%).Results:The clinical manifestations were diverse. Most patients received amphotericin B liposome and/or fluconazole as an initial option. The outcomes were curing (n=17, 58.8%), death from cryptococcal infection (n=5, 29.4%), partial relief (n=1, 5.9%) and stable disease (n=1, 5.9%). Among 10 curative cases, 2 cases died from other causes and 4 cases returned to hemodialysis with graft loss.Conclusions:Cryptococcosis is typically a late-occurring infection in kidney transplant recipients. Many factors, such as complications, nonstandard antifungal treatment, immune dysbalance, have adverse prognoses. Strengthening follow-ups, dealing with complications, validating the diagnosis early, interdepartmental cooperations, standardizing antifungal therapy and balancing immune status may improve the outcomes of cryptococcosis after kidney transplantation.
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BACKGROUND:Retinol binding protein-4 is a most sensitive biomarker for loss of function of the human proximal renal tubule, which is applied in the early detection of acute kidney injury. It is speculated that retinol binding protein-4 may be associated with acute rejection and delayed graft function after renal transplantation. OBJECTIVE: To investigate the correlation of peripheral blood retinol binding protein-4 and renal alograft function in the early stage after renal transplantation. METHODS:The venous blood samples of renal transplantation recipients were continuously colected for detection. As a retrospective nested case-control study, 20 cases of clinical diagnosed acute rejection were selected as acute rejection group. Another 20 cases of delayed graft function and 20 cases with normal graft function were randomly selected according to the ratio of 1:1:1 and taken as delayed graft function group and control group, respectively. Retinol binding protein-4 level was detected by the immune turbidimetric method, and meanwhile, the serum creatinine and blood urea nitrogen levels were dynamicaly examined by the sarcosine oxidase method. Then, al the data were comparatively analyzed at vertical and horizontal levels. RESULTS AND CONCLUSION:Compared with the control group, retinol binding protein-4 and serum creatinine levels in the acute rejection group and the delayed graft function group were significantly higher (P < 0.05). Retinol binding protein-4 and serum creatinine levels in the acute rejection group were significantly different between the rejection and non-rejection periods (P < 0.01). Similarly, these two indicators in the delayed graft function group were significantly different between the normal and abnormal renal function periods (P < 0.05). Retinol binding protein-4 levels were positively correlated with serum creatinine and blood urea nitrogen levels. Both in the acute rejection group and delayed graft function group, retinol binding protein-4 levels changed earlier than the serum creatinine levels. Retinol binding protein-4, an independent biomarker indicator, is positively correlated with serum creatinine and blood urea nitrogen and has certain time advantage in predicting the change of renal function, which is very conducive to the clinical diagnosis and monitoring of acute rejection and delayed graft function.
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Abstract BACKGROUND: Calcium dobesilate (calcium dihydroxy-2, 5-benzenesulfonate) has been widely used to treat chronic venous insufficiency and diabetic retinopathy, especialy many clinical studies showed that calcium dobesilate as vasoprotective compound ameliorates renal lesions in diabetic nephropathy. However, there are few literatures reported calcium dobesilate in the treatment of chronic renal alograft dysfunction after renal transplantation. OBJECTIVE:To observe the efficacy and safety of calcium dobesilate on chronic renal dysfunction after renal transplantation. METHODS:A total of 152 patients with chronic renal alograft dysfunction after renal transplantation were enroled from the Military Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University of Chinese PLA. They were randomly divided into the treatment group (n=78) and the control group (n=74). Patients in the treatment group received 500 mg of calcium dobesilate three times daily for eight weeks. Al patients were treated with calcineurin inhibitor-based triple immunosuppressive protocols and comprehensive therapies. RESULTS AND CONCLUSION: For patients receiving calcium dobesilate, serum creatinine, blood urea nitrogen and uric acid decreased significantly at two weeks after treatment and maintained a stable level (P 0.05). Administration of calcium dobesilate did not change the general condition of patients with renal insufficiency, nor did it affect blood concentrations of the immunosuppressive agents. Calcium dobesilate may help to delay the progress of graft injury in patients with chronic renal graft dysfunction by conjugating with creatinine, ameliorating the impaired microcirculation and its antioxidant property. The decline in serum creatinine aleviates patients’ anxiety and concern arising from the elevation of creatinine. However, the negative interference with serum creatinine caused by calcium dobesilate should be cautious in order to avoid misjudgment of patients’ condition.
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Objective To investigate correlation between microRNA (miR-494) and TH 17 cell differentiation in murine cervical heterotopic cardiac transplant model.Method The heterotopic cardiac transplant models of Balb/c→C57BL/6 mice were established as experimental group,and those of C57BL/6→C57BL/6 mice as control group.Real time-polymerase chain reaction(PCR) was used to detect miR-494 and interleukin(IL)-17A mRNA expression in the grafts.CD4+ T cells,CD8+ T cells and CD45+ myeloid cells were isolated from the grafts,and miR-494 and IL-17 mRNA expression was detected.In vitro,lymphocytes in the spleen from C57BL/6 mice were harvested,and CD4+ T cells were isolated with MACS and then stimulated to TH 1,TH 2,TH 17,Treg subset cells.The expression of IL-17A mRNA and miR-494 in different T subsets was examined by Reverse transcription-polymerase chain reaction(RT-PCR).Result Two grafts from each study group were harvested on the 7th day post-transplantation.In experimental group,the IL-17A mRNA expression was increased,while the expression of miR-494 was decreased as compared with control group with the difference being significant between two groups.The expression of IL-17A rnRNA in CD4+ T cells of the grafts was significantly increased,while that expression of miR-494 was decreased.In vitro,the expression of miR-494 in TH 17 cells was significantly lower than that in TH 1,TH 2 and Treg cells.Conclusion miR-494 is related closely to TH 17 cells differentiation in the transplant rejection,which may play a role in transplant rejection through regulating TH 17 cells.
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BACKGROUND:Fol ow-up researches have shown that there is no statistical y difference in safety between kidney donor and healthy person after kidney transplantation, even the donors wil have better life quality. OBJECTIVE:To evaluate the safety of living-related kidney transplantation in living kidney donors. METHODS:Ninety-four cases of kidney donors received 1-10 years fol ow-up through regular clinical fol ow-up, telephone fol ow-up and regular renal patients self-help groups to compare the changes of serum creatinine, hematuria, proteinuria and blood pressure and lipid level in the donors before and after kidney transplantation. RESULTS AND CONCLUSION:The serum creatinine was significantly increased after nephrectomy (P0.05). After nephrectomy, three cases (3.2%) suffered from hematuria, two cases (2.1%) had proteinuria, and improved after rest;six cases (6.4%) were subject to hypertension and six cases (6.4%) to hyperlipidemia. Al of the donors were alive. The living donor nephrectomy is feasible and safe. Preoperative assessment and long-term postoperative fol ow-up can guarantee the safety of the donors.
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Objective To investigate the correlation between urine levels of IP-10,Mig,OPG and the occurrence of renal allograft rejection.Methods As a retrospective nested case-control study,biopsy confirmed acute rejection reaction by 20 cases was rejection group,and recovery of renal function in kidney transplant after the elect good by 20 cases was control group.morning urine was tested of IP-10,Mig and OPG level of the two groups within 30 d after transplantation.The advantage was taken of the Luminex 2000 test platform,through PlexMark triple kidney injury marker kit to detect the daily urine of recipients.Results The rejection group's urinary IP10 wa (394.7 ± 67.3)ng/L,significantly higher than that in the control group of (10.9 ± 3.8) ng/L (P＜0,05).Urine Mig level of rejection group was (443.0 ± 88.9) ng/L,and the control group was only (15.7 ± 6.99)ng/L.Rejection group was significantly higher than that in the control group (P＜0.05).Urine OPG peak levels,the difference between the two groups was not statistically significant.Rejection group in the rejection period urinary IP-10 and Mig levels were significantly non-exclusion period,the difference was statistically significant (P＜0.01) higher than its level at different times with serum creatinine concentration showed obvious correlation,IP-10 with serum creatinine of correlation coefficients (R2)=0.8673,P＜0.01,Mig and serum creatinine R2 =0.7951,P＜0.01,IP-10 and Mig change time earlier than serum creatinine,to the exclusion of the before and after OPG differences no statistically significant.Conclusion The increasing of IP-1O and Mig content in the urine is associated with acute renal allograft rejection,which is an early reflect of subclinical tubular injury.And its changes as early as elevated serum creatinine,is expected to become independent indicators to predict acute rejection reaction occurs.
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Objective To investigate the efficacy and safety of conversion therapy to mizoribine (MZR) for renal transplant patients who suffered MMF or Aza adverse reaction. Methods In 56 patients with adverse reactions at different time points after renal transplantation, there were 23 cases of pulmonary infection, 14 cases of bone marrow depression, 6 cases of hepatic functional lesion and 13 cases of diarrhea. The immunosuppressive protocols of these patients were changed to CNI + MZR + Pre when the adverse reaction occurred. During the follow-up period (11 to 53 months), the effect and adverse events of conversion treatment were observed. Results After conversion treatment, 1 of 23 patients with pulmonary infection was re-infected after 26 months and finally died of heart and lung function failure. In 14 patients with bone marrow depression, blood test returned to normal in 13cases. Six patients with hepatic functional lesion were administered hepatoprotection treatment and their liver function was restored without recurrence of impaired liver function. All 13 patients with diarrhea were relieved without recurrence. The serum creatinine was 123 ± 21.3 μmol/L and 119±18. 2 μmol/L before and after the conversion therapy respectively (P＞0. 05). During the follow-up period, all patients' graft function was good. The incidence of rejection was 1.7 % (1 case). Nine patients (16. 1 %) had a higher level of uric acid after conversion. One patient had finger and toe joint pain. The symptoms were relieved after symptomatic treatment. Conclusion There were high security and good effect of conversion therapy to MZR due to MMF or Aza adverse reaction. Besides, MZR conversion therapy for renal transplantation patients provided a new option for individual immunosuppression.
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Objective To compare the efficacy and safety of conversion from CCB to ARB in the treatment of hypertension and proteinuria in kidney transplant recipients.Methods 127 long-term recipients who used CCB as their anti-hypertensive drug were enrolled.All recipients had stable renal function and no diabetes.Recipients were randomly assigned to experimental group (65 cases) which received ARB (Losartan,50～ 100 mg/day) instead of CCB,or control group (62 cases) which received routine CCB.All recipients were followed up for 2 years.Blood count,urinalysis,liver and kidney chemistry,blood lipid,serum electrolytes,24-h urine protein,blood concentration of CNI drugs and other biochemical indexes were observed.Results During the 2-year follow-up,the blood pressure of the two groups was maintained within normal level.The 24-h urine protein was decreased in the experimental group ( 176.32 ± 54.54 to 155.69 ± 62.25,P＜0.05),but increased slightly in the control group (P＞0.05).Although the blood lipid of the experimental group was not different before and after the follow-up,the high density lipoprotein (HDL) was increased statistically (2.25 ± 0.26 to 2.46 ±0.31,P＜0.05).The blood count,liver and kidney chemistry,serum potassium,blood concentration of CNI drugs in both groups showed no significant differences.Conclusion Both CCB and ARB could be effectively and safely used for the treatment of hypertension and proteinuria in kidney transplant recipients.ARB would be more effective in reducing cardiovascular disease (CVD)rate and decreasing proteinuria.
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Objective To discuss the diagnosis and treatment of invasive aspergillosis(IA)of lung after kidney transplantation. Methods Ten cases of IA infection of lung after kidney transplantation from January 1999 to May 2006 were reviewed.Among 10 cases.all had been examined by FOB and 3 positive.Six cases had a typical sign of IA in chest CT.Five cases had GM positive. Results Eight cases were cured including 3 cases with itraconazole,5 with amphotericin B.The other 2 died of infection. Conclusions Invasive pulmonary aspergillosis is a severe complication of renal transplantation.Early diagnosis and proper treatment can reduce the mortality.
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Objective To compare the difference of clinical and laboratory characteristics between the patients undergoing uninephrectomy for urologic diseases and healthy living kidney donors.Methods The change of blood pressure,renal function,blood routine examination,urine protein,plasma electrolytes and blood fat in two groups preoperatively and at one week,one month,6 months and one year postoperatively were retrospectively assessed.Of the 65 living kidney donors,12 were male and 53 were female.Among 354 cases of uninephrectomy for urologic diseases,there were 291 cases of hpper urinary tract tumor,56 cases of hydronephrosis and 7 cases of severe kidney injury.Results Compared to the preoperative status,there was significant difference of hemoglobin,creatinine,urea nitrogen and urine protein in two groups.Clinical and laboratory characteristics of two groups became stable at one months postoperatively,and could reach the preoperative level at 6 months or one year postoperatively.But the creatinine was 25.71%higher than the preoperative level in healthy donors and 25.49%in patients undergoing uninephrectomy for urologic diseases.There was no significant difference between the two groups at one year postoperatively.Conclusions Two groups are safety after nephrectomy.There is no significant difference of clinical and laboratory characteristics between the 2 groups.Strict donor selection,appropriate pretransplantation evaluation,careful operation and postoperative health consulting play important roles in donors;safety and health.