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1.
Article in English | WPRIM | ID: wpr-922552

ABSTRACT

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,

2.
Chinese Journal of Nephrology ; (12): 286-293, 2020.
Article in Chinese | WPRIM | ID: wpr-870961

ABSTRACT

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.

3.
Article in Chinese | WPRIM | ID: wpr-870570

ABSTRACT

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.

4.
Organ Transplantation ; (6): 316-2020.
Article in Chinese | WPRIM | ID: wpr-817612

ABSTRACT

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.

5.
Article in Chinese | WPRIM | ID: wpr-755903

ABSTRACT

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 .

6.
Chinese Journal of Nephrology ; (12): 487-490, 2015.
Article in Chinese | WPRIM | ID: wpr-482928

ABSTRACT

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.

7.
Article in Chinese | WPRIM | ID: wpr-444428

ABSTRACT

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.

8.
Article in Chinese | WPRIM | ID: wpr-389105

ABSTRACT

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.

9.
Article in Chinese | WPRIM | ID: wpr-392000

ABSTRACT

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.

10.
Chinese Journal of Nephrology ; (12): 538-542, 2009.
Article in Chinese | WPRIM | ID: wpr-380729

ABSTRACT

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.

11.
Acta Pharmaceutica Sinica ; (12): 148-150, 2001.
Article in Chinese | WPRIM | ID: wpr-411312

ABSTRACT

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.

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