ABSTRACT
Here we report the diagnosis and treatment of a rare IgG4-related kidney disease with nephrotic syndrome as the first manifestation. A 62-year-old male patient, presented with edema in both lower limbs and foam urine, had a history of "lung malignant tumor with brain and lymph node metastasis". The increase of IgG4 and decrease of glomerular filtration rate were detected at admission, and the pathological consideration of renal biopsy was membranous nephropathy with IgG4-related tubulointerstitial nephritis. After the combination of low-dose glucocorticoids therapy and rituximab treatment, the patient showed good prognosis in a 9 month follow-up.
ABSTRACT
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.
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.