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Objective:To explore clinicopathological features and prognosis of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in children induced by antithyroid drugs.Methods:The clinicopathological features, treatment and prognosis of 3 children with AAV induced by antithyroid drugs in the Department of Pediatric Nephrology and Rheumatology of the First Affiliated Hospital of Sun Yat-sen University were analyzed retrospectively, and the literatures were reviewed.Results:(1) Among the 3 cases, there were 2 females and 1 male, whose ages were 12.6, 13.9 and 13.1 years old, respectively. All patients had medication history of propylthiouracil (PTU) and/or methimazole (MMI) before onset. Initial manifestation was pallor and renal involvements with nephrotic proteinuria, hematuria and renal function abnormality, while 2 of them had hypertension. Extrarenal manifestations were also presented: case 1 presented with rash, arthralgia and cardiac insufficiency; case 2 had brain involvement with repeated convulsions; case 3 presented with arthralgia and lung involvement. They were all tested positive for p-ANCA and MPO-ANCA. Initial renal histopathology of the 3 cases were consistent with ANCA-associated glomerulonephritis, which were classified into sclerosis, crescentic and mixed class respectively. After 8 months of treatments, repeated renal biopsy of case 3 had demonstrated progression to sclerosis class. Antithyroid drugs (PTU or MMI) were discontinued in 3 cases, and the children were all treated with corticosteroid combined with intravenous pulse cyclophosphamide therapy. Plasma exchange was performed in case 2 and case 3 due to rapidly progressive glomerulonephritis and disease recurrence (suspected pulmonary hemorrhage), respectively. Case 3 was treated with rituximab combined with mycophenolate mofetil after recurrence. The extrarenal symptoms relieved quickly after treatments in all cases. P-ANCA and MPO-ANCA became negative in case 1 and case 2 after 6 months of treatments but they were persistently positive in case 3. Three cases were followed up for 24 months, 10 months and 12 months, respectively: case 1 develop chronic kidney disease (CKD) stage 2 with normal urinalysis; case 2 develop CKD stage 5 and had sudden death at home at 10-month follow-up; case 3 develop CKD stage 4 with nephrotic proteinuria and microscopic hematuria. (2) There were totally 30 pediatric cases with AAV induced by PTU and MMI, including 27 reported cases in the literature and 3 cases in this study. Symptoms of AAV appeared in children after an average administration of (37.5±4.0) months of PTU (range from one month to 96 months and 8 months of MMI alone). Kidney (28 cases, 93.3%) and lung (12 cases, 40.0%) were commonly involved, while brain (2 cases, 6.7%) was rarely involved. The pathological changes of kidney were crescent nephritis (5/23) and necrotizing pauci-immune complex nephritis (11/23). The total remission rate was 93.3% (28/30) after antithyroid drugs withdrawal and treatment with corticosteroids and immunosuppressive therapy, however, there were still severe cases with progression to CKD stage 5, and death. (3) Thirty cases were divided into complete response group ( n=19) and incomplete response group ( n=11) according to the treatment response. Compared with complete response group, the proportions of massive proteinuria (8/11 vs 5/19), fibrinoid necrosis (7/9 vs 4/14), deposition of immune complex in renal tissues (6/9 vs 2/14) and administration of immunosuppressants (10/11 vs 5/19), and degree of tubular atrophy (0/1/2/3 grade, 2/4/2/1 vs 9/5/0/0) in incomplete response group were higher (all P<0.05). Conclusions:PTU and MMI can both induce AAV in children, and AAV may occur after short-term course of administration. Kidney and lung are commonly involved while brain involvement is rarely seen. Timely withdrawal of antithyroid drugs and proper treatments with corticosteroids and immunosuppressants can result in high remission rate, though there are still some severe cases. Nephrotic-range proteinuria, renal fibrinoid necrosis, immune-complex deposition and tubular atrophy may be the risk factors of AAV for poor prognosis.
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Objective To analyze the relationship between the serum B-cell activating factor (BAFF) levels and clinical characters and pathological features in children with lupus nephritis (LN). Methods ELISA was used to detect the serum BAFF (sBAFF) levels of the 54 LN children diagnosed in the First Affiliated Hospital, Sun Yat-sen University during October 1, 2014 to December 31, 2016 and with complete clinical data. According to whether glucocorticoid or immunosuppressive agents has been used at their first admission, patients were divided into treated group (n=44) and non-therapy group (n=10). According to the renal response after induction treatment for 6 months, patients were divided into remission group (n=20) and non-response group (n=34). According to whether there was renal recurrence, they were divided into recurrence group (6 cases) and non-recurrence group (48 cases). According to renal biopsy, patients were divided into class-Ⅲ, class-Ⅳ and class-Ⅴ group. Another 15 healthy children were taken as a control group. The correlations between sBAFF and clinical manifestation, laboratory examination, renal biopsy and clinical outcome were analyzed. Results (1) Compared with the control group, the sBAFF was significantly increased in LN group (t=3.821, P<0.001). Compared with the non- neuropsychiatric systemic lupus erythematosus (NPSLE) group, sBAFF was significantly increased in NPSLE group (t=2.202, P=0.032). (2) Compared with that in treated group, sBAFF was significantly higher in untreated group (LSD - t=2.309, P=0.025). Compared with non-response group, sBAFF was significantly decreased in response group (LSD-t=2.035, P=0.046). (3) No significant difference was observed between class-Ⅲ, class-Ⅳ and class-Ⅴpathological classification group (F=1.080, P=0.459). sBAFF in LN children was not significantly correlated with the active index (AI) or chronic index (CI) of Austin index (r=-0.273, P=0.063; r=0.150, P=0.314). (4) In LN children, sBAFF has positive correlation with ESR and IgG level (r=0.289, P=0.036; r=0.340, P=0.017) and negative correlation with WBC (r=-0.337, P=0.013). Multiple linear regression model showed that serum IgG level (β'=0.517, P=0.001) and renal response (β'=-0.271, P=0.037) were independent influencing factors of sBAFF level. Conclusions Renal remission and serum IgG levels in LN children are influencing factors of sBAFF levels. sBAFF is helpful to clinical assessment on renal response of LN children.
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Objective To investigate the clinical, pathological features and risk factors of hyperuricemia in children with IgA nephropathy (IgAN). Methods A retrospective study of 269 primary IgAN children diagnosed between January 1, 2006 to December 31, 2017 at the Children Kidney Disease Center, the First Affiliated Hospital of Sun Yat-sen University, was performed in the hyperuricemia group (uric acid>350 μmol/L) and the normal uric acid group. The clinical and pathological characteristics were analyzed, and the risk factors of hyperuricemia were analyzed by using multivariate logistic regression analysis. Results There were 185 males and 84 females in the 269 IgAN children with age of (9.2 ± 3.1) years old, among whom there were 70 patients (26.0％) accompanied by hyperuricemia. Clinical indicators such as hypertension, urea nitrogen, serum creatinine, blood lipids, urinary protein in hyperuricemia group were higher than those in normal uric acid group (all P<0.05), while estimated glomerular filtration rate, serum total protein and albumin were less (all P<0.05). There were 58 patients (23.0％) and 12 patients (70.5％) associated with hyperuricemia among IgAN children with CKD 1-2 and CKD 3-5. The proportion of hyperuricemia in CKD stage 3-5 IgAN children was statistically higher than that in normal uric acid group (P<0.01). The hyperuricemia group had a higher proportion of Lee IV and V grade, and a lower proportion of the Lee III grade than the normal uric acid group (all P<0.05). According to the Oxford pathological classification score, there was no significant difference in total scores of renal lesions, glomerular score, and tubulointerstitial score between the two groups (all P>0.05). According to the Katafuchi semi-quantitative score, there was no significant difference in the total scores of renal lesions, glomeruli, and tubulointerstitial scores (all P>0.05), while the hyperuricemia group had higher renal vascular scores than the normal uric acid group (P<0.01). Multivariate logistic regression analysis showed that hypertension (OR=12.596, 95％CI 1.778-89.243, P=0.011), higher total cholesterol (OR=1.192, 95％CI 1.064-1.336, P=0.002), higher urea nitrogen (OR=1.273, 95％CI 1.104-1.468, P=0.001), proteinuria 3+(OR=1.875, 95％CI 1.309-2.684, P=0.001), proteinuria 4+(OR=1.627, 95％CI 1.241-2.134, P<0.001) and CKD stage 3 (OR=3.355, 95％CI 1.376-8.181, P=0.008) were the risk factors of hyperuricemia in children with IgAN. Conclusions Twenty-six percent IgAN children patients are accompanied by hyperuricemia, and their clinical parameters and pathological changes are more severe than those in normal uric acid group. Hypertension, higher total cholesterol, higher urea nitrogen, proteinuria 3+/4+and CKD stage 3 are the risk factors of hyperuricemia in children with IgAN.