ABSTRACT
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.
ABSTRACT
Objective:To investigate the impact of different type of dyslipidemia on clinical and pathological characteristics in children with IgA nephropathy (IgAN).Methods:A retrospective study was performed at the Children Kidney Disease Center, the First Affiliated Hospital of Sun Yat-sen University between January 2006 to September 2019. Children diagnosed with primary IgAN was divided into dyslipidemia group and normal blood lipid group according to whether the blood lipid is normal, and was divided into the following four groups: hypercholesterolemia group, hypertriglyceridemia group, mixed hyperlipidemia group and low high-density lipoprotein cholesterol (HDL-C) group according to clinical classification. The clinical and pathological features in different groups were analyzed, and the risk factors of dyslipidemia were analyzed by using multivariate logistic regression analysis.Results:A total of 252 children with IgAN were enrolled in this study, including 169 males and 83 females, with a male/female ratio of 2.04∶1 and an age of (9.3±3.1) years. Among them, 34.5% IgAN children were complicated with hypertension, and 170 cases (67.5%) were in dyslipidemia group, 82 cases (32.5%) in normal blood lipid group. According to clinical classification, the children in dyslipidemia group were divided into hypercholesterolemia group (58 cases, 23.0%), hypertriglyceridemia group (16 cases, 6.3%), mixed hyperlipidemia group (77 cases, 30.6%) and low HDL-C group (19 cases, 7.5%). The systolic blood pressure, diastolic blood pressure, proportion of hypertension, blood urea nitrogen, uric acid and urinary protein in dyslipidemia group were higher than those in normal blood lipid group (all P<0.05), and the levels of serum albumin, blood IgA and estimated glomerular filtration rate (eGFR) were less (all P<0.05). The proportion of IgAN children in chronic kidney disease (CKD) stage 1 and CKD stage 2-5 with dyslipidemia was 65.0% and 84.4% respectively, and the proportion of IgAN children with CKD stage 2-5 in dyslipidemia group was higher than that in normal group ( P<0.05). The dyslipidemia group had a higher proportion of Lee Ⅲ-V grade than normal blood lipid group ( P<0.01). The results of Oxford pathological classification showed that the proportions of M1 and E1 in dyslipidemia group were higher than those in normal lipid group (all P<0.05), and there was no significant difference in segmental glomerulosclerosis, tubular atrophy or interstitial fibrosis and crescent between the two groups (all P>0.05). The comparison results between groups with different types of dyslipidemia showed that systolic blood pressure, diastolic blood pressure, serum uric acid and urinary protein in the mixed hyperlipidemia group were higher than those in other groups (all P<0.05), and the serum albumin level was less ( P<0.01). The results of Oxford pathological classification showed that the proportion of E1 in hypercholesterolemia group and mixed hyperlipidemia group was higher ( P<0.05). Multivariate logistic regression analysis showed that hypertension ( OR=2.734, 95% CI 1.327-5.632, P=0.006) and low serum albumin ( OR=0.838, 95% CI 0.791-0.889, P<0.001) were the risk factors of dyslipidemia in children with IgAN. Conclusions:In our center, 67.5% IgAN children are accompanied by dyslipidemia. The clinical manifestations and pathological changes of these dyslipidemia children are more severe than those with normal blood lipid, and the IgAN children with mixed hyperlipidemia are more notable. Hypertension and low serum albumin are the risk factors of dyslipidemia in children with IgAN.