ABSTRACT
Objective:To investigate the role of the NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome and its downstream interleukin(IL)-1β, IL-6, and IL-18 in the pathogenesis of antineutrophil cytoplasmic antibody-associated vasculitis(AAV) in children.Methods:A retrospective study was conducted.Specifically, the localization and expression of the NLRP3 inflammasome in renal tissues of 22 children who were diagnosed with primary AAV and underwent renal biopsy in the Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital of Sun Yat-Sen University from September 2003 to September 2020 were detected by the immunohistochemical method.The IL-1β, IL-6 and IL-18 levels in serum and urine were measured by enzyme-linked immunosorbent assay.The measurement data conforming to normal distribution were compared by the t test between two groups and by the single factor ANOVA test among multiple groups.The measurement data that did not conform to normal distribution were compared by the Wilcoxon signed rank sum test.Classification variables were examined by the χ2 test. Pearson correlation coefficient or Spearman rank correlation coefficient were used to analyze the correlation among variables. Results:NLRP3 was widely expressed in the tubulointerstitium, and the expression level in the active group was higher than that in the control group, the semi-quantitative scores of NLRP3 in the renal tubule and glomeruli in the active group were higher than those in the control group ( F=0.859, 8.320, all P<0.05). In the active group, the semi-quantitative score of NLRP3 in the renal tubule was higher than that in the glomeruli( F=3.517, P<0.05). The semi-quantitative score of NLRP3 in the renal tubule was positively correlated with the pediatric vasculitis activity score at renal biopsy ( r=0.471, P=0.027)and negatively correlated with the estimated glomerular filtration rate at renal biopsy ( r=-0.548, P=0.008)in the active group.The serum IL-1β, serum IL-18 and urinary IL-6 levels in the active group were higher than those in the remission group and the control group ( F=16.449, 16.449, 0.637, 29.891, 27.612, 7.464, all P<0.05). The serum IL-18 level in the remission group was higher than that in the control group( F=18.671, P<0.05). In the active group, a positive correlation was found between the serum IL-1β level and the semi-quantitative score of NLRP3 in the renal tubule( r=0.805, P=0.002), between the serum IL-6 level and the C-reactive protein level at renal biopsy ( r=0.728, P=0.017), and between the urinary IL-6 level and the crescent proportion at renal biopsy ( r=0.677, P=0.032). The serum IL-18 level in the active group was positively correlated with the semi-quantitative score of NLRP3 in the renal tubule, pediatric vasculitis activity score and glomerular sclerosis proportion at renal biopsy, and negatively correlated with the estimated glomerular filtration rate at renal biopsy ( r=0.644, 0.612, 0.695, -0.577, all P<0.05). The urinary IL-18 level was positively correlated with the complement C 4 level at renal biopsy ( r=0.855, P<0.05). Conclusions:The NLRP3 inflammasome and its downstream IL-1β, IL-6, and IL-18 may be involved in the pathogenesis and progression of AAV, and can be used as one of the reference indicators for disease activity assessment.
ABSTRACT
Objective@#To investigate the clinicopathological features of IgA nephropathy(IgAN) complicated with acute kidney injury (AKI) in children.@*Methods@#The clinical and pathological data of children with biopsy-proven primary IgAN and complicated with AKI from January 2012 to December 2016 in the First Affiliated Hospital of Zhengzhou University were analyzed retrospectively, and the data of macroscopic hematuria (MH) associated AKI(15 cases) and other MH without AKI(99 cases) were compared.@*Results@#(1) Among 211 patients diagnosed with IgAN, 21 (9.95%) patients were complicated with AKI.Among the 21 cases, the average age was (9.5±2.1) years old, in which 17 cases(80.9%) were males, 19 cases with MH, and the range of the peak serum creatinine was 93-627 μmol/L.In histology, cellular/fibrocellular crescents were found in 11 cases, while high proportion of tubules filled with red blood cell(RBC) casts were observed in 8 cases, and moderate to severe acute tubular injury (ATI) were observed in 16 cases.In 2 cases, extensively mixed inflammatory cell infiltration with eosinophils was present in the interstitium.(2) According to the clinical and pathological characteristics, the 21 cases were divided into 3 groups: 15 cases with MH related AKI, 4 cases with crescentic glomerulonephritis, and 2 cases with acute interstitial nephritis.Compared with MH without AKI group(99 cases), the MH associated AKI group(15 cases) had significantly longer duration of MH, higher proteinuria level, urinary levels of β2-microglobulin (β2-MG) and N-acetyl-β-D-glucosaminidase (NAG), and greater frequency of RBC casts and ATI, and the differences were statistically significant(all P<0.05). In 2 acute interstitial nephritis cases, one had a history of taking weight loss drug with unknown ingredients, while the specific cause of the other was not clear.(3) None of the patients was on dialysis, but corticosteroid was prescribed in 17 cases (including methylprednisolone pulse therapy in 6), and 3 cases were combined with cyclophosphamide.Almost all patients achieved normal renal function except for one who had no response within 2 months after treatment.The median follow-up period was 24 months, in which 1 patient with crescentic glomerulonephritis progressed to end-stage renal disease.@*Conclusions@#AKI is commonly seen in children with IgAN, and complete recovery of renal function was seen in all patients with MH associated AKI and acute interstitial nephritis.