Objective To evaluate the clinicopathological characteristics and prognosis of IgA nephropathy (IgAN) patients with microangiopathy lesions and with no hypertension. Methods Adult IgAN patients without hypertension were selected from Peking University First Hospital. All kidney biopsies were independently reviewed by 2 investigators. Patients were divided into three groups (microangiopathy group, simple arterio/ arteriolosclerosis group and normal vascular group) by renal arteriolar lesions. Composite kidney end point event defined as a ≥30% reduction in estimated glomerular filtration rate (eGFR) and end-stage kidney disease. Cox regression analysis was used to test the association between microangiopathy lesions and the outcomes. Results A total of 420 patients were included in this study, of which 37(8.8%) patients had renal arteriolar microangiopathy lesions, 134 (31.9%) patients had simple arterio/ arteriolosclerosis, and the others had no vascular lesion. Compared with simple arterio/ arteriolosclerosis group or non-vascular lesion group, patients with renal arteriolar microangiopathy lesions had more severe urine protein (P=0.002), worse renal function (P<0.001), higher proportion of segmental glomerulosclerosis and/or balloon adhesion (S1), tubular atrophy/interstitial fibrosis (T1/2), cellular/fibrocellular crescents (C1/2) (all P<0.05). During the follow-up, 20(54.1%) patients with microangiopathy lesions, 45(33.6%) patients with simple arterio/arteriolosclerosis and 82(32.9%) patients without vascular lesion reached the composite kidney end points (χ2=6.491, P=0.039). In a multivariable Cox regression model, the presence of microangiopathy lesions was an independent risk factor for kidney disease progression in IgAN patients (HR=1.872, 95%CI 1.044-3.357, P=0.035), and simple arterio/arteriolosclerosis was not a risk factor for kidney disease progression. Conclusion It is not uncommon for non-hypertensive patients with IgAN having microangiopathy lesions, which suggests that hypertension is not the sole risk factor for microangiopathy lesions.
Objective To observe the clinical efficacy of tacrolimus (TAC) and mycophenolate mofetil (MMF) in children with refractory IgA nephropathy (IgAN). Methods The diagnosis of refractory IgAN was defined as urinary protein level ≥ 50 mg·kg-1·d-1 after treatment with renin-angiotensin system (RAS) blocker and prednisone. Following the case-control matching method, 76 children with renal biopsy diagnosed as refractory IgAN in the Jinling Hospital from January 1, 2012 to December 31, 2016 were retrospectively selected, and the children were divided into TAC group (38 cases) and MMF group (38 cases). The 24 h urinary protein quantity (24hUP), serum albumin (Alb), serum creatinine (Scr), serum uric acid (UA), serum glucose (Glu), adverse reactions and treatment effects were compared between the two groups. Results There were no significant differences in the age, sex ratio, blood pressure, estimated glomerular filtration rate (eGFR), 24hUP, urine red blood cell count (U-RBC), Scr, Alb, BUN, aspartate transarninase (AST), alanine transarninase (ALT), Glu, pathological Oxford classification, and the proportions of big-dose methylprednisolone treatment before using immunosuppressants between the two groups (all P>0.05), and they were comparable. From 3 months after treatment, the 24hUP levels of the two groups were significantly lower than those of the baseline (all P<0.05), and the 24hUP levels of TAC group were lower than those of MMF group at 3, 6 and 12 months (all P<0.05). The Alb level of TAC group was significantly higher than the baseline value from 1 month of treatment (P<0.05), while the Alb level in the MMF group was significantly higher from 3 months of treatment (P<0.05). The Alb levels in the TAC group were higher than those in MMF group after 1, 3, and 6 month of treatment (all P<0.05), and there was no significant difference in Alb level at 12 months between the two groups. The total effective rate, complete remission rate and ineffectiveness rate of the TAC group all showed significant differences with the MMF group from 3 month of treatment (all P<0.05), but there was no difference between the two groups during the follow-up period of partial remission rate, point recurrence rate and cumulative recurrence rate (all P>0.05). The TAC group achieved the maximum effective rate at 6 months (94.7%), while the MMF group achieved the maximum effective rate at 12 months (68.4%), and the difference was statistically significant (χ2=8.756, P=0.003). The incidence of adverse reactions in two groups had not significant difference (15.8% vs 21.1%, χ2=0.350, P=0.554). However, the blood glucose of TAC group was higher than that of MMF group in the third month of treatment, and the difference was statistically significant [5.02(4.72, 5.22) mmol/L vs 4.42 (4.19, 5.07) mmol/L, Z=-2.745, P=0.006]. Conclusion Both TAC and MMF in the treatment of refractory IgAN result in a good treatment effect in children, but the TAC reaches the response level faster and the response rate is higher.
Objective To analyze the changes of helper T cell 22 (Th22) and related cytokines and chemokines in patients with IgA nephropathy (IgAN) and tonsillitis, and explore its relationship with clinical pathological changes. Methods IgAN patients who were diagnosed at the Xiangya Hospital of Central South University from June 2015 to June 2016 were included. They were divided into IgAN and tonsillitis (IgAN+tonsillitis) group, IgAN group, mesangial proliferative glomerulonephritis (MsPGN) group and control group (HC) group according to renal pathology and whether associated with tonsillitis. Flow cytometry was used to detect the percentage of peripheral blood Th17, Th22 cells, CC-type chemokine receptor (CCR) 4, CCR6 and CCR10 cells. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of interleukin (IL)-22, IL-1β, IL-6, TNF-α, CCL22, CCL20 and CCL27. Immunohistochemical method (IHC) was used to detect the expression of CCL22, CCL20 and CCL27 in kidney tissue. The differences of clinicopathological indicators, the proportion of Th22 cells and related chemokine in each group were compared and analyzed. Results A total of 44 IgAN patients were included, including 14 patients complicated with tonsillitis. Ten MsPGN patients and 16 healthy people were also included. There was no statistically significant difference in gender, age, blood pressure, kidney function, blood lipid and other biochemical indicators among the groups (all P>0.05). The peripheral blood Th22 cells and CCR10 positive cells in the IgAN group, MsPGN group, and IgAN+tonsillitis group were significantly higher than those of the control group, and serum IL-22, IL-1β, IL-6, TNF-α, CCL20, CCL22 and CCL27 levels were also significantly higher (all P<0.05). All above indexes reached the highest levels in IgAN patients combined with tonsillitis. The changes of CCL20, CCL22 and CCL27 in renal tissues were consistent with those in peripheral blood. The percentage of Th22 cells increased in hematuria-positive and higher MEST scores patients. Conclusions Th22 cells cooperated with CCL27/CCR10 axis are involved in the pathogenesis of IgAN. Tonsillitis exacerbates clinical severity and kidney injury of IgAN.
Objective To investigate the relationship between plasma factor VIII (FVIII) level and the clinical indicators and prognosis in IgA nephropathy (IgAN) patients. Methods The clinical data of IgAN patients diagnosed from the Second Xiangya Hospital of Central South University from January 2016 to December 2016 were collected. Patients were divided into high FVIII group (FVIII>140.50%) and low FVIII group (FVIII≤140.50%) according to the time-dependent receiver operating characteristic curve analysis. The baseline clinical parameters at the time of renal biopsy between two groups of patients were compared. Taking the estimated glomerular filtration rate (eGFR) reduction ≥30% or entering end-stage renal disease (ESRD) as the endpoint event, Kaplan-Meier analysis and Cox proportional hazards models were used to explore the association between plasma FVIII level and prognosis in IgAN patients. Results A total of 93 patients were ultimately retained for this study, with a median follow-up of 35.15(33.77, 36.76) months. Twelve (12.90%) patients reached the endpoint event. The levels of serum creatinine, urea nitrogen, triglyceride, total cholesterol, plasma fibrinogen, D-dimer, 24-hour urinary protein, protein C, protein S, slope of eGFR and age in the high FVIII group were higher than those in the low FVIII group (all P<0.05). The levels of eGFR, serum albumin and follow-up time in the high FVIII group were lower than those in the low FVIII group (all P<0.05). The renal cumulative survival rate was significantly lower in the high FVIII group than that in the low FVIII group (χ2=5.635, P=0.018) according to the Kaplan-Meier analysis. After adjusting for variables such as systolic blood pressure, eGFR, urinary protein, and renal tubular atrophy/interstitial fibrosis, multivariate Cox proportional hazards models analysis showed that high level of plasma FVIII was an independent risk factor for poor prognosis in IgAN patients (HR=4.147, 95%CI 1.055-16.308, P=0.042). Conclusions The level of plasma FVIII is associated with clinical indicators and prognosis in IgAN patients. The higher level of plasma FVIII can be identified as an independent risk factor for poor prognosis in IgAN patients.
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 m2)-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 m2)-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.
Objective To assess the value of urine heat-shock protein-70 (HSP-70) in the early diagnosis of acute kidney injury (AKI) after cardiac cardiopulmonary bypass (CPB). Methods Patients with cardiopulmonary bypass from May 2018 to July 2018 in Henan Provincial People's Hospital were enrolled as subjects. Urine samples were collected before and after cardiopulmonary bypass at 0 h, 2 h, 4 h, 6 h, 8 h, 12 h, 24 h and 48 h. Patients were divided into AKI group and non-AKI group according to the Kidney Disease: Improving Global Outcomes Guide. Urinary HSP-70, tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) were detected by enzyme-linked immunosorbent assay (ELISA) and urine neutrophil gelatinase-associated lipocalin (NGAL) was determined by immunoturbidimetry. The receiver operating characteristic (ROC) curve was plotted to calculate the critical value, sensitivity and specificity of urine HSP-70, [TIMP-2]×[IGFBP7] and NGAL for the diagnosis of postoperative AKI after CPB. Results A total of 45 patients were enrolled in the study. There were 24 cases in AKI group and 21 cases in non-AKI group. The level of urinary HSP-70, [TIMP-2]×[IGFBP7] and NGAL in AKI group were significantly higher than in the non-AKI group at each postoperative time point, with statistically significant differences (all P<0.05). The level of urinary HSP-70 in AKI group peaked at 2 h after CPB, which was significantly earlier than the peak time of urine [TIMP-2]×[IGFBP7] and urine NGAL (12 h after CBP and 4 h after CBP, respectively). Urinary HSP-70≥2.1 μg/L could predict postoperative AKI of CPB at 2 h after CPB, with the area under the curve (AUC) of 1.00, the sensitivity of 100.0% and the specificity of 100.0%. Urinary [TIMP-2]×[IGFBP7]>19.1 μg2/L2 could predict postoperative AKI of CPB at 12 h after CPB with the AUC of 0.94, the sensitivity of 87.5%, and the specificity of 100.0%. Urinary NGAL>27.4 μg/L could predict postoperative AKI of CPB at 4 h after CPB with the AUC of 0.95, the sensitivity of 95.8%, and the specificity of 85.7%. The positive predictive value of urine HSP-70≥2.1 μg/L at 2 h after CPB was 100.0%, and the negative predictive value was 100.0%. Conclusions The level of urinary HSP-70 increases earlier than that of urinary [TIMP-2]×[IGFBP7] and NGAL in patients with AKI after CPB. Clinical monitoring of urinary HSP-70 level contributes to early diagnosis of AKI.
Objective To analyze the related factors affecting the use of autogenous arteriovenous fistula (AVF), and provide a theoretical basis for prolonging the service life of AVF in hemodialysis patients. Methods This was a retrospective study. The patients undergoing AVF and using it to maintain hemodialysis (MHD) in the First Affiliated Hospital of Nanchang University from October 2004 to June 2017 were selected as study subjects to discuss the relevant factors affecting the service life of AVF. The data of general information, dialysis and laboratory examinations were collected through questionnaire surveys, hospital case system and hemodialysis record sheets. The patients were divided into the patency group and the dysfunction group according to the status of AVF, and the related factors were compared. Multivariate Cox proportional hazard model was used to analyze the influencing factors, and Kaplan-Meier survival curve was used to determine the service life of AVF, respectively. Results A total of 187 subjects were included in the study. The patency group had 140 cases and the dysfunction group had 47 cases. There were statistically significant differences in the proportion of diabetes, the level of serum albumin, uric acid and parathyroid hormone (PTH) between the two groups (all P<0.05). Multivariate Cox proportional hazard regression analysis showed that diabetes (HR=9.348, 95%CI 3.507-24.918, P<0.001) and hypoalbuminemia (HR=12.650, 95%CI 2.925-54.714, P=0.001) were risk factors for the short service life of AVF. The results of Kaplan-Meier analysis showed that the service life of AVF in patients with diabetes was significantly shorter than that in MHD patients without diabetes (Log-rank χ2=13.191, P<0.001); the service life of AVF in patients with hypoalbuminemia was significantly shorter than that without hypoalbuminemia (Log-rank χ2=13.591, P<0.001). Conclusions Diabetes mellitus and hypoalbuminemia are risk factors for the short service life of AVF. Therefore, intervention programs should be formulated to extend the service life of AVF.