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There is currently a huge worldwide demand for donor kidneys for organ transplantation. Consequently, numerous marginal donor kidneys, such as kidneys with microthrombi, are used to save patients' lives. While some studies have shown an association between the presence of microthrombi in donor kidneys and an increased risk for delayed graft function (DGF) (McCall et al., 2003; Gao et al., 2019), other studies have demonstrated that microthrombi negatively impact the rate of DGF (Batra et al., 2016; Hansen et al., 2018), but not graft survival rate (McCall et al., 2003; Batra et al., 2016; Gao et al., 2019). In contrast, Hansen et al. (2018) concluded that fibrin thrombi were not only associated with reduced graft function six months post-transplantation but also with increased graft loss within the first year of transplantation. On the other hand, Batra et al. (2016) found no significant differences in the DGF rate or one-year graft function between recipients in diffuse and focal microthrombi groups. To date, however, the overall influence of donor kidney microthrombi and the degree of influence on prognosis remain controversial, necessitating further research.
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Humans , Thrombotic Microangiopathies , Transplantation, Homologous , Tissue Donors , Kidney , AllograftsABSTRACT
Objective:To explore the influencing factors of acute rejection (AR) within one year after pediatric kidney transplantation (KT) and the effect of AR onset time on prognosis.Methods:From January 2011 to October 2021, a total of 112 patients aged under 18 years at the time of transplantation were selected.After excluding 6 of them with early renal non-function caused by non-rejection, 106 cases were examined.There were 63 males and 43 females with the age of 15(12, 16) years.The donors were living related (n=26) and deceased (n=80).According to the presence/absence and onset time of AR, they were assigned into three groups of AR within one year, AR after one year and non-AR.The relevant clinical data of donor/recipient, influencing factors of AR and therapeutic outcomes of AR were retrospectively compared.One-way ANOVA or Kruskal-Wallis test was utilized for comparing 1-year renal function after the occurrence of AR among three groups.With graft-function loss as an end-point event of follow-up, the effects of AR within one year and AR after one year on survival rate and function of graft-kidney were analyzed by Kaplan-Meier survival curve.Results:The median follow-up period of 106 pediatric KT recipients was 35 months.During follow-ups, 19 episodes of AR occurred in 17(16.0%) patients and 89 recipients exhibited no AR episode by the end of follow-up (non-AR group).As for initial AR, 9 episodes of AR occurred within one year (AR within one year group) and 8 episodes of AR after one year (AR after one year group).After anti-rejection treatment, 8 patients (47.1%) achieved full recovery and 6 patients (35.3%) failed to completely normalize and 3 patients (17.6%) developed graft failure.Univariate analysis indicated that, as compared with non-AR group, female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 were risk factors of AR within one year ( P=0.032, P=0.039, P=0.047).Kaplan-Meier survival analysis revealed that the incidence rates of AR within one year in patients with donors aged under 8 years and early postoperative parvoviral infection were 14.5%(8/55) and 30.0%(3/10) respectively.They were significantly higher than 2.0%(1/51) and 6.3%(6/96) of patients with donors aged above 8 years and those without parvoviral infection ( P=0.012, P=0.004).With graft-function loss as an end-point event of follow-up, Kaplan-Meier survival analysis showed that 10-year kidney graft survival rate in AR within one year and AR after one year groups were 88.9% and 65.6%.Both were significantly lower than that in non-AR group (98.9%).And the inter-group differences were statistically significant ( χ2=4.286, P=0.038; χ2=7.787, P=0.005).However, no significant difference existed in survival rate between AR within one year and AR after one year groups ( P=0.689).One-way ANOVA and Kruskal-Wallis test indicated that estimated glomerular filtration rates at 3/6/12 months after an onset of AR in AR within one year group were (76.8±51.6), (80.6±56.6) and (85.6±40.2) ml·min -1·1.73 m -2.The values of 3/6 months were lower than (125.3±39.2) and (124.7±38.2) ml·min -1·1.73 m -2 in AR after one year group.And the inter-group differences were statistically significant ( P=0.021, P=0.039).The values of 3/6/12 months were lower than (112.2±34.2), (115.3±33.2) and (117.4±30.2) ml·min -1·1.73 m -2 in non-AR group.And the inter-group differences were also statistically significant ( P=0.019, P=0.020, P=0.020). Conclusions:Female recipients, donors aged under 8 years and early postoperative infection with parvovirus B19 may elevate the risks of AR in children within one year of KT.AR within one year affects the survival rate of graft-kidney and renal function.
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BK polyomavirus-associated nephropathy (BKPyVAN) is a common cause of allograft failure. However, differentiation between BKPyVAN and type I T cell-mediated rejection (TCMR) is challenging when simian virus 40 (SV40) staining is negative, because of the similarities in histopathology. This study investigated whether donor-derived cell-free DNA (ddcfDNA) can be used to differentiate BKPyVAN. Target region capture sequencing was applied to detect the ddcfDNAs of 12 recipients with stable graft function, 22 with type I TCMR, 21 with proven BKPyVAN, and 5 with possible PyVAN. We found that urinary ddcfDNA levels were upregulated in recipients with graft injury, whereas plasma ddcfDNA levels were comparable for all groups. The median urinary concentrations and fractions of ddcfDNA in proven BKPyVAN recipients were significantly higher than those in type I TCMR recipients (10.4 vs. 6.1 ng/mL,
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Objective:To investigate the cause of the allograft IgA nephropathy (IgAN) recurrence or de novo, and the risk factors for the graft-survival in allograft IgAN. Methods:Patients from the First Affiliated Hospital of Zhejiang University Medical College who were diagnosed as a transplanted kidney IgAN by allo-renal biopsy during November 2012 to December 2018 were selected. According to the increased levels of serum creatinine and the descent rate of estimated glomerular filtration rate (eGFR) on the last follow up, the patients were divided into the graft-function stable group (increased Scr<20 μmol/L, eGFR descent rate<10%), the graft-function inadequacy progressive group (Scr increased but less than doubling increase, 30%<eGFR descent rate<60%) and the graft-function lost group [double increase in serum creatinine and eGFR down to<15 ml·min -1· (1.73 m 2) -1 to chronic kidney disease stage V]. The clinical data and pathological characteristics were retrospectively analyzed and compared in the three groups. Taking the eGFR drop to<15 ml·min -1·(1.73 m 2) -1 to chronic kidney disease stage V as the end point event of follow-up, the effects of tacrolimus (FK506) concentration, the quantity of proteinuria and pathological changes of graft-renal on the survival rate of graft-renal were analyzed by Kaplan-Meier survival curve. Results:At the time of allograft biopsy, the urine protein/creatinine ratio (UP/Cr) was (2.00±2.38) g/g in the 38 cases, and the serum creatine increased in 17 cases (44.7%). Meanwhile, the blood concentration of FK506 was< 4 μg/L in 16 of 29 (55.2%) cases who taken FK506. With (23.2±22.2) months follow-up after renal biopsy, 11 cases (28.9%) progressed in renal insufficiency (graft-function inadequacy progressive group), and 7 cases (18.4%) lost their graft-function (graft-function lost group). The UP/Cr on the biopsy was significantly higher in graft-function lost group than that in graft-function stable group ( P=0.001), and the blood concentration of tacrolimus before biopsy was significantly lower in graft-function lost group than that in graft-function stable group [(3.05±0.71) μg/L vs (5.03±1.62) μg/L, P<0.010]. Kaplan-Meier survival analysis showed the kidney graft survival rate was significantly lower in the groups with a lower concentration of tacrolimus before the biopsy, with a large amount of proteinuria at the time of biopsy than that in the concentration of tacrolimus≥4.0 μg/L, and UP/Cr<2.3 g/g groups ( P=0.020, P=0.001, respectively), and with a infiltrated inflammatory cells in renal glomerular capillary loops and a co-deposition of C1q in mesangial region groups than that no infiltrated inflammatory cells in renal glomerular capillary loops and no co-deposition of C1q in mesangial region groups ( P=0.042, P=0.015, respectively). Conclusions:The low concentration of tacrolimus is the cause of the recurrence or de novo of allograft IgAN. A large amount of proteinuria, the inflammatory cells infiltration in glomerular capillary, the C1q deposition in mesangial region and the low concentration of tacrolimus are the factors that affect the survival rate of graft-renal IgAN.
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Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.
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Objective:To explore the clinical prognosis of early endarteritis (within 2 weeks) and late endarteritis (after 2 weeks) after renal transplantation.Methods:A total of 81 cases with higher creatinineand receiving renal biopsy after renal transplantation were recruited from September 2001 to December 2014. They were divided into early endarteritis group (n=43) and late endarteritis group (n=38). Baseline profiles, serum creatine, glomerular filtration rate (GFR) before and after treatment, steroid resistance, reversal rate, graft loss and survival rate were analyzed for two groups.Results:Early endarteritis group showed worse serum creatine and GFR than late endarteritis group before rejection. Early endarteritis group had a higher rate of treatment with steroid plus antibody (86 %) than that of late endarteritis group (86 %vs.18.6 %, P<0.05). No significant inter-group difference existed in graft loss (23.3 % vs.10.5 %, P=0.131). The survival curve of transplanted kidney showed no significant inter-group difference insurvival time. Conclusions:The status of patients with early simple endothelitis is significantly worse than that of those with late simple endothelitis. However, after active treatments, the prognosis of patients with early simple endothelitis is not inferior to that of those with late simple endothelitis.
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Objective To explore the clinical characteristics of tertiary hyperparathyroidism (THPT) after renal transplantation .Methods The levels of bone mineral density (BMD) , serum calcium , phosphates , alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH ) were retrospectively analyzed in 36 RTx recipients with persistent hypercalcemia and stable kidney function (eGFR 76 .71 ± 17 .44) ml/min/1 .73 m2 .Results Among them ,serum total calcium level increased (2 .97 ± 0 .20 ) mmol/L for 6 to 170 months ,blood phosphorus decreased (0 .59 ± 0 .19 ) mmol/L , serum alkaline phosphatase (ALP) increased to (295 .73 ± 194 .22)U/L and T-score of BMD decreased (T - 2 .78 ± 0 .84 in lumbar vertebrae and T - 2 .09 ± 0 .66 in hip joint) .And 11 /36 (30 .6％ ) cases had a complication of extraosseous calcification .Parathyroid hyperplasia was detected in 17 /36 cases (47 .2％ ) .iPTH was significantly higher at pre-operation and 1 week post-operation than that in control group (n= 45) (859 .50 ± 495 .44 vs 345 .56 ± 216 .55 pg/ml) , P = 0 .001 ,(759 .25 ± 907 .07 vs 197 .45 ± 249 .31 pg/ml) , P= 0 .001 .The value of iPTH at the last follow-up (198 .26 ± 155 .22) pg/ml was still higher than normal reference value (15 .0 - 65 .0 pg/ml) . Multivariate stepwise regression analysis showed the last iPTH was correlated with preoperative iPTH ,serum calcium and postoperative serum phosphor ,ALP and 25OHD3 (P= 0 .024 , P= 0 .002 , P = 0 .001 , P = 0 .037 , P = 0 .026 ) .Conclusions Renal recipients had a higher levels iPTH with persistent hypercalcemia , hypophosphatemia , osteoporosis and extraosseous calcification showing the features of tertiary hyperparathyroidism .
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Objective To observe the clinical characteristics of 2 patients with mucolipidosis type Ⅲ. Methods Two sibling patients (a sister and a brother) with mucolipidosis type Ⅲ symptoms and other family members were the research objects, and the changes of their features of hand bone imaging, blood indexes [blood glucose, cholesterol, triacylglycerol (TG), total protein (TP), albumin (Alb)] and body composition were analyzed. Results Except the 2 patients, the bone morphology, blood indexes and body compositions in other 7 family members were under normal conditions. The phalanx intervals of both hands in 2 patients with mucolipidosis type Ⅲwere widened significantly, among them the thumb manifestation was more obvious; the distal segments of phalanxes in both hands became pointed and curved presenting a "claw-like hand" deformity; the metacarpal and distal carpal metaphysis were obviously enlarged, and scaphoid, lunate, trianglar, orbicular, and trapezium and trapezoid bones were loosely arranged at the wrist; the distal ends of ulna and radius were markedly enlarged. Compared to healthy people, the triglyceride levels of serum in the 2 patients were obviously reduced (the percentage of reduction: 57.14% and 41.07% respectively); body mass indexes (BMI), total fat and visceral fat were significantly lowered (BMI reduction percentage:26.81% and 14.55%, total fat reduction percentage: 38.12% and 44.95%, visceral fat reduction percentage: 62.25% and 67.74%, respectively) in the two patients. Conclusion The purpose of studying the biochemistry indexes, imaging characteristics and body compositions is to more deeply understand the clinical symptoms and signs of the 2 sibling patients with mucolipidosis type Ⅲ in a family to provide a theoretical reference.
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Objective To explore the origin of ovarian high grade serous carcinoma(HGSC) through analysing the expression and significance of PAX8,PAX2,p53 and RAS in the ovary and fallopian tube of different types and grades of serous carcinoma. Methods A total of 44 cases tissue samples of ovarian tumor including 34 malignant ovarian tumor and 10 normal normal tissue (as control group) were collected from the admitted patients in Affiliated Tumor Hospital of Guangxi Medical University from January 2015 to January 2016. Fallopian tube tissues were segmented in accordance with the fimbria, ampulla, isthmus and the corresponding ovarian tissues were by the side. There were 34 cases of patients with ovarian cancer including 29 cases of epithelial ovarian cancer (27 serous carcinoma, 1 mucinous carcinoma,1 endometrioid adenocarcinoma)and 5 non-epithelial ovarian cancer(sex cord-interstitial tumor). Among 27 cases of patients with ovarian serous cancer,there were 23 HGSC and 4 low-grade ovarian serous cancer (LGSC). One hundred fifty-three cases of samples were diagnosed as ovarian serous cancer by Shandong University Affiliated Qilu Hospital from 2005 to 2013 and these samples were made tissue microarray.(1)To analyze the expression and differences of PAX8,PAX2,p53 and RAS in the above tissues and tissue microarray from ovarian and tubal of HGSC and control women by immunohistochemistry methods.(2)To compare the expression levels of PAX8,PAX2,p53 and RAS in ovarian and fallopian tubes of ovarian cancer patients with different pathological types. (3) To analyze the correlations of tubal and ovarian tissue in PAX8,PAX2,p53 and RAS expression of HGSC.(4)To analyze the factors of the prognosis of ovarian serous cancer in tissue microarray by single factor analysis method. Results (1)PAX8,PAX2, p53 and RAS expression was negative in normal ovarian epithelium of control group,but the expression of PAX8, PAX2, p53 and RAS were strongly positive brown in secrete cells of normal fallopian tube epithelium.(2)p53 and RAS expression of fallopian tube epithelium in the epithelial ovarian cancer group were significantly higher than those in the non-epithelial ovarian cancer groups(P<0.05),but the expression of PAX8 and PAX2 in fallopian tube and the expression of PAX8,PAX2,p53 and RAS in ovarian tissue was not statistically significant in the groups(P>0.05).PAX8,PAX2 and p53 expression of the ovarian in HGSC group were significantly higher than those in LGSC group(P<0.05),while the expression of RAS was lower in the ovarian of the high-grade group (P<0.05), while the expression of PAX8, PAX2, p53 and RAS in fallopian tube was not statistically significant in the groups(P>0.05).(3)There was a significantly positive correlation between fallopian tube and the corresponding ovary of HGSC in PAX8 and PAX2 expression(r=0.422, P=0.045; r=0.693, P=0.000), but not correlation in p53 and RAS expression (r=0.058, P=0.793; r=-0.190,P=0.384).(4)Univariate survival analysis showed that the progression free survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8, PAX2 and RAS(P<0.05),but there were not correlated with age,surgical staging,cell differentiation,lymph node metastasis and preoperative chemotherapy and p53 protein expression (P>0.05). The total survival time in patients with ovarian serous cancer group was significantly correlated with the protein expression of PAX8 (P<0.05),but there were not correlated with age,surgical staging,cell differentiation,lymph node metastasis and preoperative chemotherapy and the protein expression of PAX2, RAS and p53 (P>0.05). Conclusions PAX8, PAX2, p53, RAS are of great significance for the study of origin of HGSC. HGSC may be derived from fallopian tube, but further investigation would be necessary to confirm this. PAX8, PAX2, p53, RAS could be expected to be used as predictors of survival prognosis in patients with ovarian serous cancer.
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Objective To discuss the pathogenesis of the statin-induced rhabdomyolysis in renal transplant recipients.Methods We presented two renal transplant recipients who developed rhabdomyolysis in 2012 in our hospital.The clinical presentation,laboratory results,diagnosis and treatment of the two patients were analyzed retrospectively.The basic immunosuppressive agent of two patients was cyclosporine A.The recipients developed rhabdomyolysis following simvastatin lipidlowering therapy,and one patient suffered acute renal failure simultaneously.Acute tubular injury was confirmed by renal biopsy.Finally,the symptoms of the two patients were relieved completely,creatine kinase (CK) returned to normal after the satins discontinued and saline,sodium bicarbonate and diuretics were given.The renal failure patient underwent plasma exchange and CRRT,and the renal function returned to normal.Results The level of cyclosporine A should be monitored when the renal transplant patient was given statins,especially whose basic immunosuppressive agent was cyclosporine A.At the same time we should pay more attention to the symptoms of the myotoxic side effects and avoid using the drug which was also metabolized by CYP3A4.Conclusion Physicians should be aware of the potential risks of combined therapy of statins which are metabolized by P450CYP3A4 and cyclosporine A in transplant patients.If using it is advisable to begin with small dosage and monitor the CK level.
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The delivery of therapeutical agents for brain tumors′ treatment is enormously prevented by the presence of blood‐brain barrier .Nano‐carriers such as nano‐particles ,liposomes and micelles can significantly increase the transport of drugs across the blood‐brain barrier .The dual‐targeting nano‐carriers modified by one or two functional groups can further increase the brain delivery of drugs as well as their accumulation in brain tumors ,resulting in significant improvement in the diagnosis and therapy of brain tumors .This article mainly focused on the recent development of strategies and functional groups of dual‐targeting nano‐carriers ,providing a reference for relevant investigations .
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<p><b>OBJECTIVE</b>To investigate the expression and clinical significance of miRNA-155 and miRNA-146a in peripheral blood mononuclear cells (PBMC) and plasma of oral lichen planus (OLP) patients.</p><p><b>METHODS</b>Twenty-five female and seven male OLP patients (OLP group) aged 25 to 54 years were selected from January 2012 to May 2013. The diagnosis was confirmed by pathology and the lesions were divided into two non-erosive OLP group (18 cases) and erosive OLP group (14 cases). Twenty healthy sex and age matched volunteers served as control. miRNA-155 and miRNA-146a expressions in PBMC and plasma were examined by real-time PCR. The difference between OLP group and control group was statistically analyzed.</p><p><b>RESULTS</b>The expressions of PBMC and plasma miRNA-155 were higher in OLP patients than those in the healthy control (median, 0.07 vs 0.03, P < 0.05; 5.84 vs 1.32, P < 0.01). The median expression level of miRNA-146a in PBMC and plasma of OLP patients and healthy controls were (1.26 vs 0.58, P < 0.05) and (412.60 vs 238.42, P < 0.01). The plasma miRNA-155 and miRNA-146a expressions were significantly higher in erosive OLP group than those in non-erosive OLP group. There were no significant differences in the expression of PBMC miRNA-155 and miRNA-146a between the two groups.</p><p><b>CONCLUSIONS</b>The expressions of PBMC and plasma miRNA-155 and miRNA-146a are higher in OLP patients. The expressions of plasma miRNA-155 and miRNA-146a are associated with OLP severity. The over expression of miRNA-155 and miRNA-146a in OLP may play a role in the pathogenesis of OLP.</p>
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Adult , Female , Humans , Male , Middle Aged , Leukocytes, Mononuclear , Metabolism , Lichen Planus, Oral , Metabolism , Pathology , MicroRNAs , Metabolism , Real-Time Polymerase Chain ReactionABSTRACT
Objective To analyze the early renal function of donors after nephrectomy.Methods Clinical data of 467 cases of living kidney donors during the period from April,2010 and November,2014 in our center were retrospectively analyzed.Data on serum creatinine (Scr),glomerular filtration rate (GFR),serum uric acid (UA),and urine microproteins before operation and three days,seven days,one month and three months after operation were collected to evaluate the impact of nephrectomy on early renal function after operation for donators.Results Before operation and three days,seven days,one month,three months after operation,the average serum creatinine (Scr) level was (59.9±12.8),(85.8±21.0),(91.2±21.3),(92.8±21.6),(91.0±21.3) μmol/L,respectively; The GFR were (113.5±25.3),(75.1± 17.9),(70.3± 15.2),(68.5± 16.0),(69.5± 15.1) ml/min,respectively; The levels of uric acid were (292.60±79.58),(142.18±55.28),(228.41±66.39),(321.31± 83.72),(346.61±87.21) μmol/L,respectively; All these data above-mentioned after operation reached statistical significance compared with that before operation (P ＜ 0.05).Parameters including urine IgG,urine albumin,urine retinol-binding protein and urine β2-microglobulin post-operation time point were significantly different when compared with relative parameters pre-operation (P ＜ 0.05).Conclusions Nephrectomy has significant influence on GFR,uric acid,and urine microprotein for donors in the early stage after operation.It's worth to evaluate nephrectomy's long-term effect on the renal function of donors in clinical practice.
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Objective To observe the effect and safety of Ginkgo biloba extract (EGb) in patients with chronic allograft nephropathy (CAN),and to study the clinical protective mechanism of EGb.Method A prospective,non-randomized,controlled study was conducted on 103 cases of CAN from March 2013 to March 2015.All patients were divided into experimental group (group A,53 cases) and control group (group B,50 cases).The group A was treated with EGb.Patients were followed up for at least 6 months.Before and after treatment,the changes in renal hemodynamic parameters were observed.The biochemical parameters were also observed,including 24-h urinary protein,urinary albumin,serum creatinine (Scr),triglyceride (TG),total cholesterol (TC),estimated glomerular filtration rate (eGFR),platelet count (PLT),fibrinogen (FIB),D-dimer (DD),activated partial thromboplastin time (APTT).The clinical efficacy and safety were analyzed.Result (1) Therewere no significant differences in clinical and biochemical parameters between the two groups before treatment (P＞0.05).(2) After treatment,the systolic peak flow velocity (Vmax) of segmental artery and arcuate artery in the experimental group was significantly higher than in the control group,and the resistance index (RI) in the experimental group was significantly lower than that in the control group,P＜0.05.(3) In both two groups,the 24-h urinary protein,urinaryalbumin,TG,TC and Scr were decreased after treatment (P＜0.05),and eGFR was elevated (P＜0.05).Moreover,the changes in 24-h urinary protein and urinary albumin in the experimental group were more significant than the control group after treatment (P＜0.05).(3) PLT,FIB and DD in experimental group were significantly decreased after treatment,and APTT was increased significantly (P＜0.05).PLT,FIB,DD and APTT had significant change after treatment in the experimental group as compared with control group.(4) There were no significant differences in adverse reactions between two groups (x2 =0.047,P =0.828).Conclusion The therapy of EGb in patients with CAN could reduce urinary protein and improve hypercoagulable state,and had few adverse reaction with good security.
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Objective To study the effects of CYP3A5 * 1 and CYP3A5 * 3 genotypes on tacrolimus dose requirement.Method We tested archival peripheral blood of 69 kidney recipients for CYP3A5 genotyping by polymerase chain reaction.The dose,blood concentrations and dose-normalized blood concentrations of tacrolimus were measured at 1st and 2nd month after the renal transplantation.Result There were 6 cases of CYP3A5 * 1/* 1 (8.7％),22 cases of CYP3A5 * 1/* 3 (31.9％),and 41 cases of CYP3A5 * 3/* 3 (59.4％).At 1st and 2nd month after the renal transplantation,the carriers of CYP3A5 * 1 genotype had a higher mean tacrolimus dose than CYP3A5 * 3/* 3 genotye (both P＜0.000 1),and those of CYP3A5 * 1 genotype had lower mean tacrolimus concentrations than CYP3A5 * 3/* 3 genotye (P=0.020 8,and P =0.019 1 respectively).Meanwhile,the carriers of CYP3A5 * 1 genotype had lower dose-normalized blood concentrations of tacrolimus than CYP3A5 * 3/* 3 genotye (P＜0.000 1) at 1st month after the renal transplantation,as well as at 2nd month after the renal transplantation (P =0.0191).Hepatic and renal function showed no significant effect on tacrolimus dose adjusted concentration at 1st and 2nd month after transplantation.Gender did not show a significant impact on tacrolimus dose.Conclusion CYP3A5 * 1 carriers needhigher tacrolimus dose than CYP3A5 * 3 homozygote to achieve the target blood concentration.CYP3A5 genotyping is a new approach for detecting tacrolimus dose requirement in kidney recipients.
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Objective To evaluate the value of immune cell functional assay (ImmuKnow CD4+ T cell ATP assay) in monitoring immune status in renal recipients.Methods A total of 131 adult renal transplant recipients who received transplantation for the first time were under investigation.According to the dynamic monitoring ATP concentration before operation,2 week,1,3,6 months after operation and during infect or rejection,samples were divided into the following groups:health control group (HC),pretransplant (Pre-Tx) group,stable (Tx) group,infect group,acute rejection (AR) group,acute kidney injury (AKI) group.Immune cell functions were detected by ImmuKnow CD4+ T cell ATP assay.Lymphocyte subsets (CD4+/CD8+) were analysed and serum concentrations of FK506 were tested.Mixed lymphocyte reaction(MLR) was analysed.Results The ATP concentration was no significant difference between Pre-Tx and HC group.The ATP concentration of 2 weeks,1 months after operation were significantly higher than Pre-Tx group (P ＜ 0.01).After 3 months,6 months follow-up,the ATP concentration stabilized with time.The ATP concentration of AR group was significantly higher than other three groups (Tx,infect and AKI group,all P ＜ 0.05).The correlation coefficient between the ATP concentration and MLR,CD4+/CD8+,FK506 level were R2=0.0072,R2=10-6,R2=0.004 respectively (all P ＞ 0.05).Conclusions The cell-mediated immunity of recipients is relatively strongger during the first month after transplantation.The ATP concentration is not related to the levels of MLR,CD4+/CD8+,FK506.ImmuKnow ATP assay is a valuable predictor in acute rejection diagnosis.
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Objective To compare the long-term effectiveness of anti-interleukin-2 receptor antibodies vs.rabbit antithymocyte globulin as induction therapy in kidney transplantation.Methods Between 2006 and 2010,371 recipients of kidney transplants were treated with calcineurin inhibitors (CNI),mycophenolate mofetil and prednisone.261 patients of them received induction therapy with anti-interleukin-2 receptor antibodies (IL2Ra group),and 88 patients received rabbit antithymocyte globulin (rATG group).All the patients received ganciclovir against cytomegalovirus and SMZ against pneumocystis carinii.The data of delayed graft function (DGF),the rate of acute rejectin (AR) and infection in the first year and patient/allograft long survival rate in two groups were retrospectively analyzed during a follow-up period of 1 to 5 years postoperatively.Results There was no significant difference in the sex,age and causes of end-stage renal disease between the two groups.The rATG group had more kidney transplants from deceased donors (P＜0.01 ) and the cold ischemia time was longer than that of the IL2Ra group (P＜0.01 ).The IL2Ra group and the rATG group had similar incidence of DGF (3.1％ vs.1.8％,P＞0.05).One year after operation,the incidence of AR in IL2Ra group and rATG group was 10.7％ and 2.7％ respectively (P＜0.05),and the incidence of infection in IL2Ra group and rATG group was 14.9％ and 21.8％ respectively (P＞0.05).One-,two- and three-year patient survival rate in IL2Ra group was 98.9％,98.9％ and 98.5％ respectively,and that in rATG group was all 98.2％ (P＞0.05).The one-,two- and three-year allograft survival rate in IL2Ra group was 98.5％,98.1％ and 97.7％ respectively,and that in rATG group was all 97.3％ (P＞0.05).Conclusion rATG is more effective than IL2Ra preventing from acute rejection and does not increase the risk of infection for induction in kidney transplant recipients.
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Objective To elucidate the clinical features of nutcracker syndrome complicated with IgA nephropathy (IgAN) and to increase its level of diagnosis and treatment. Methods Clinical data of 14 cases of nutcracker syndrome complicated with IgA nephropathy (patient group) and 36 cases of nutcracker syndrome (control group) were analyzed retrospectively. Nutcracker syndrome was diagnosed by ultrasonography and magnetic resonance angiography (MRA) and IgAN by renal biopsy. Differences of clinical data and images in two groups were analyzed. Results Gender, age and blood pressure of two groups were not significantly different. Higher Scr level [(81.2±21.3) μmol/L vs (61.2±11.8) μmol/L, P<0.01], more severe proteinuria [(1.1 ± 0.6) g/d vs (0.3±0.2) g/d, P<0.01] and hematuria (2.3±0.9 vs 1.5±1.3, P<0.05) in patient group were found. Differences of ultrasonography and MRA in two groups were not significant. Conclusion Renal biopsy should be considered in cases of nutcracker syndrome with persistence of proteinuria, hematuria or abnormal morphology of urinary red blood cell.
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Objective To explore the effect of acute humoral rejection on kidney graft survival.Methods 1098 patients received cadaveric renal transplant from January 2002 to December 2008 in our center. All patients were given triple immunosuppressants including tacrolimus or cyclosporine.According to patients who experienced biopsy-proved humoral rejection and cellular rejection within one year post-transplant, there were 53 cases in humoral rejection group, 109 in cellular rejection group (including 63 patients with borderline change), and 936 in normal group. Patients who experienced acute rejection received mythyl-prednisolone pulse, or received anti-CD3 antibody/plasma exchange/globulin. Clinical characteristics before operation including sex, age, HLA mismatch, panel reactive antibody, cold/warm ischemic time, graft loss rate and graft survival were compared among three groups. The effect of completely reversed cellular rejection and humoral rejection on graft survival was analyzed. Results There was no significant difference in sex, age and cold ischemic time among three groups, but there was significant difference in warm ischemic time, level of PRA and HLA mismatch between cellular rejection group or humor rejection group and normal group (P＜0. 05). During a follow-up period, the incidence of graft loss in humoral rejection group was 27.4 %, significantly higher than 7.3 % in cellular rejection group and 2.2 % in normal group, P＜0. 001. Kaplan-Meier analysis revealed the survival rate of grafts in humoral rejection group was significantly lower than in cellular rejection group and normal group (P＜0.001 ). After patients with irreversible rejection were excluded,there was no significant difference in the survival rate of grafts among the three groups.Conclusion Patients with acute humoral rejection survived with inferior graft outcome,but completely reversible rejection showed no effect on the graft survival.
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Aim To explore the effect of microRNAs on the differentiation of 3T3-L1 adipocytes and the expression of adipo-related gene-fatty acid binding protein during the adipocyte differentiation.Methods adipo-related microRNAs during 3T3-L1 adipocyte differentiation were screened and identified by micorRNA microarray.Constructed high-expression plasmids of the adipo-related microRNAs,were transfected into the 3T3-L1 preadipocytes by lipofectamine.While the effect of adipo-related microRNAs on the course of 3T3-L1 adipocyte differentiation was observed,the protein and mRNA expression level of fatty acid binding protein(FABP4)were analyzed by Western blot and RT-PCR during 3T3-L1 adipocyte differentiation.Results The expression profiles of microRNAs have significant changed during 3T3-L1 adipocyte differentiation,in which 35 microRNAs among them down-relation,the most lowly expression is miR-24;17 microRNAs among them up-relation,the most highly expression is miR-21.MiR-24 significantly inhibited adipocyte differentiation and maturity,while miR-21 have no significant effect.MiR-24 significantly inhibited the expression of FABP4,but had no effect on the level of its mRNA;miR-21 had no effect on the expression of protein and mRNA of FABP4.Conclusion There exist adipogenic-related microRNAs during 3T3-L1 adipocyte differentiation; miR-24 play an important role in the regulation of 3T3-L1 preadipocyte differentiation into adipocyte and the(FABP4)protein expression.