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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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Objective:By retrospectively analyzing 6 cases of IgG4-related membranous nephropathy (IgG4-MN), combined with literature review, to explore the clinical and renal pathological characteristics of the disease, and improve clinicians' understanding of the disease.Methods:The data of six patients with biopsy-proven IgG4-MN in the nephrology center of our hospital during April 2017 to January 2021 were collected. At the same time, we reviewed the literature systematically and summarized the clinicopathological characteristics.Results:Six male patients with the age ranged fom 55 to 75 years old were described. Urine protein level was (3.1±2.1) g/24 h, 3 cases (50%) showed nephrotic syndrome and 4 cases (67%) had elevated serum creatinine. The median creatinine level was (103±24) μmol/L. Six cases (100%) had elevated serum immunoglobulin (Ig)E level, and 4 cases (67%) had elevated IgG4. M-type phospholipase A2 receptor (PLA2R) was positive in 1 case (17%) and tubulointerstitial nephritis (TIN) was present in 6 cases. The review of the literature suggested that a total of 49 cases with IgG4-MN were reported, including 6 cases in this report. There were 40 males (40/46, 87%), with a age range of (61±12) years old, 32 cases (32/49, 65%) showed nephrotic syndrome range proteinuria, and the proportion of serum IgG and IgG4 increase was 61%(20/33) and 88% (36/41), respectively, 13 cases (13/15, 87%) had elevated serum IgE level, 47% (14/30) had low-complement C3 and 44%(12/27) had low-complement C4 level. The main organs involved were pancreas (15/37) and lymph nodes (16/37). Renal pathology showed TIN in 74%(36/49). Electron dense deposition was mainly subepithelial deposits. 7%(2/28) were positive for anti-PLA2R antibody in serum, 17%(3/18) were positive for PLA2R in kidney tissue, 6%(1/18) were suspected positive for PLA2R in kidney tissue, and 8%(1/12) were dual positive in blood and kidney tissue.Conclusion:IgG4-MN usually presents with nephrotic range proteinuria or nephrotic syndrome in middle-aged and elderly patients. Most of them are complicated with TIN and other organ involvement. A certain proportion of patients are PLA2R positive in IgG4-MN, and whether it is primary or secondary MN needs further study.
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Objective:To explore the value of detecting plasma donor-derived free DNA (dd-cfDNA) fraction in distinguishing antibody mediated-rejection (ABMR) and T cell-mediated rejection (TCMR) of renal allografts.Methods:Patients with acute rejection confirmed by allograft biopsy in the First Affiliated Hospital of Medical College of Zhejiang University from December 1, 2017 to July 18, 2019 were retrospectively included. Based on pathological classification of Banff renal allograft rejection in 2017, the patients were divided into ABMR group and TCMR group, and the latter was subdivided into TCMR Ⅰ subgroup and TCMR Ⅱ subgroup. The second generation sequencing and target region capture were used to detect candidates' peripheral blood dd-cfDNA. The demographic and clinicopathological data of the two groups were compared. The receiver operating characteristic curve (ROC) was used to evaluate the differential value of plasma dd-cfDNA and serum creatinine levels in two kinds of acute renal allograft rejection.Results:A total of 60 patients with acute rejection of renal transplantation were enrolled in this study, including 42 patients in TCMR group and 18 patients in ABMR group. The plasma dd-cfDNA percentage (%) in the ABMR group was significantly higher than that in the TCMR group [2.33(1.19, 4.30)% vs 0.98(0.50, 1.82)%, P=0.001]. The absolute value of dd-cfDNA in ABMR group was obviously higher than that in TCMR group [0.94(0.60, 2.27) ng/ml vs 0.43(0.20, 0.96) ng/ml, P=0.003]. ROC analysis to discriminate TCMR from ABMR showed that, the area under the curve ( AUC) of dd-cfDNA% was 0.76(95% CI 0.64-0.88), when the threshold was 1.11%, the sensitivity and specificity were 88.89% and 59.52%, respectively; the AUC of absolute value of dd-cfDNA was 0.74(95% CI 0.61-0.86), when the threshold was 0.53 ng/ml, the sensitivity was 88.89% and the specificity was 54.76%. TCMR subgroups were further analyzed, there was no significant difference between TCMR subgroups on the absolute value and percentage of dd-cfDNA (both P>0.05); dd-cfDNA% in ABMR group was apparently higher than that in TCMRⅠ subgroups ( P=0.008) and TCMRⅡsubgroup ( P=0.030). The absolute value of dd-cfDNA in ABMR group was significantly higher than that in TCMRⅠsubgroups ( P=0.003). Conclusion:Plasma dd-cfDNA level may help to distinguish between ABMR and TCMR rejection.
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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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In the second half of 2019, the last four sessions of Transplant Cloud College jointly established by Chinese Research Hospital Association and Medical Neighbor Network were successfully held. During the courses in the second half of this year, the lecturers from each institution mainly focused upon four topics including management of hyperuricemia (HUA) after kidney transplantation, renal graft pathology, diagnosis and treatment of acute antibody-mediated rejection (AMR) after kidney transplantation and pulmonary infection after liver transplantation. All participants delivered discussions and exchanges in kidney and liver transplantation from multiple perspectives.
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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 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 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 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 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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Objective To evaluate the effects of different strategies on short-and long-term clinical outcomes of renal transplantation in Chinese subjects.Methods 2520 renal transplantations were retrospectively evaluated,including 2490 first renal transplantations and 30 second renal transplantations.Triple-immunosuppressant including cyclosporine A,azathioprine or myeophenolate mofetil(MMF)and prednisone(Pred)was adopted.Patients receiving kidney transplantation were given low dose immunosuppressants since 2000.Immunosuppressants including tacrolimus,MMF and Pred were adopted in some patients since 2000.Risk factors leading to graft loss and patients'death were analyzed.Results Until the cut date of June 30,2009,135 patients lost follow-up,and the follow-up rate was 94.6%.Incidence of acute(within 6 months post-transplantation) rejection was 18% among 2520 patients.Incidence of acute rejection (within 6 months post-transplantation) was 25.7% in panel reactive antibody (PRA) positive patients,significantly higher than 17.0% in PRA negative patients(P<0.05).Incidence of acute rejection within 6 months post-transplantation was 16.9% in HLA mismatches<4 patients,significantly lower than 23.7% in HLA≥4 patients (P<0.01).Total patient/death censored graft 1-,3-,5- and 1O-year survivals were 94.5%/96.0%,91.6%/93.1%,88.5%/90.1% and 81.7%/80.6%,respectively.Acute rejection and immunosuppressant regimen were independent risks for allograft loss.1mmunosuppressant regiment,pulmonary infection,cardio-brain-vessel accident, hepatic failure and tumor were independent risks for patients' death.Conclusion Renal allograft and patient survival appeared to be improved by optimal immunosuppressant regimen,strict HLA match and efficient post-transplant complication prophylaxis.
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Objective To investigate the effect of swifch from cyclosporine to FK506 on renal allograft outcome after initial acute rejection. Methods Clinical outcome of patients who experienced first acute rejection episode were retrospectively analyzed. After initial acute rejection, 23 patients were switched to FK506-based immunosuppression, and 63 patients continued CsA-based immunosuppression. Demographic data, lipid, serum creatinine, uric acid, incidence of recurrent acute rejection and graft survival were analyzed and compared. Results During one year after anti-rejection therapy, incidence of biopsy-proved recurrent rejection events was significantly lower with FK506 therapy (1/23, 4.35%) compared with CsA therapy (16/63, 25.40%)(P=0.033). 5-year graft survival rate of FK506-based immunosuppression group was higher than that of CsA-based immunosuppression group (100.0% vs 81.4%). Serum uric acid level of FK506-based immunosuppression group from 24 months to 36 months after initial rejection were significantly lower than that of CsA-based immunosuppression group [(265.5 ±147.9) μmol/L, (245.8±88.9) μmol/L vs (428.5±119.3) μmol/L, (441.2±125.3) μmol/L, P<0.01, respectively]. Conclusion Conversion to FK506 therapy can significantly reduce recurrent rejection episode, and decreasing serum uric acid level provides long-term benefits to graft survival.
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AIM To determine whether ONO-1078 {pranlukast, 4-oxo-8-［p-(4-phenylbutyloxy) benzoyl-amino]-2-(tetrazol-5-yl)-4H-1-benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral ischemia in mice. METHODS Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in mice. ONO-1078 (0.01, 0.05, 0.10 mg*kg-1), dexamethasone (0.5 mg*kg-1), nimodipine (0.2 mg*kg-1) or saline (control) were injected ip once daily for 3 days, and 30 min before MCA occlusion. Twenty-four hours after cerebral ischemia, the neurological scores were evaluated, infarct volumes and areas of the right and left cerebral hemispheres were measured by computer imaging analysis. RESULTS ONO-1078, dexamethasone and nimodipine reduced the neurological scores. ONO-1078 and dexamethasone reduced the ratio of right/left hemisphere area, indicating inhibition of brain edema, while nimodipine showed no effect. ONO-1078 dose-dependently reduced infarct size, and dexamethasone and nimodipine showed the same effect. CONCLUSION ONO-1078 showed protective effect on focal cerebral ischemia. This may represent a novel approach to the treatment of acute cerebral ischemia.