We performed a retrospective single-center study by reviewing the medical records and renal biopsy results of children aged ≤ 18 years, diagnosed with HSPN or IgAN from years 1998–2018 at Ramathibodi Hospital, Bangkok, Thailand. HSPN was diagnosed according to criteria defined by the American College of Rheumatology1. IgAN was diagnosed based on the results of pathology findings without the presence of extrarenal symptoms at initial diagnosis and during the follow-up period. Secondary IgAN, eg. liver disease, inflammatory bowel disease and infection-induced IgAN were excluded. All medical records were reviewed with emphasis on baseline characteristics, clinical presentation, laboratory data, pathological findings, treatments, and outcomes. Ethical permission was obtained from the Ethics Committee in Human Research of the Faculty of Medicine, Ramathibodi Hospital (ID 09-61-59 for IgAN and ID 09-61-29 for HSPN).
Hypertension was diagnosed if blood pressure (BP) ≥ the 95th percentile for age, gender and height on repeated measurements22. Proteinuria was defined as a positive protein in urine dipstick testing or urine protein-to-creatinine ratio (UPCr) ≥ 0.2 g/g. Hematuria was defined as positive blood in urine dipstick testing or ≥ 5 red blood cells per high-power on microscopic examination of a centrifuged urine specimen. Estimated glomerular filtration rate (eGFR) was calculated by the bedside CKiD equation as follows23:
eGFR = 0.413 x height (cm)/ serum creatinine (mg/dl)
All renal biopsies were performed prior to the initiation of treatment and reviewed by the two experienced renal histopathologists. Stains used for assessment were H&E, PAS, Jones and Masson’s trichrome. All specimens were examined by light microscopy, immunofluorescence staining and electron microscopy. MEST-C criteria in the updated Oxford classification were used to describe pathological data which were standardized for classification in IgA nephropathy24. The MEST-C criteria comprise of mesangial hypercellularity (with M0 and M1) corresponding to ≤ 50% and > 50% of the glomeruli showing hypercellularity, respectively), endocapillary proliferation (defined as E0, absence or E1, presence), segmental glomerulosclerosis (defined as S0, absence or S1, presence), tubular atrophy/interstitial fibrosis (with T0, T1, and T2 corresponding to ≤ 25%, 26%-50%, and > 50% of cortical area involvement, respectively), cellular/fibrocellular crescents (with C0, C1, and C2 corresponding to their absence, presence in ≥ 1 and < 25% of glomeruli, and presence in ≥ 25% of the glomeruli, respectively). This classification has been validated for use in HSPN in previous adults and pediatric studies 25, 26. However, patients who had missing data, no glomerulus presented in the renal biopsy specimens or an initial eGFR < 60 mL/min/1.73 m2 were excluded.
The treatment regimen was decided by the attending nephrologists at the time of consultation. Patients who had proteinuria with or without microscopic hematuria received enalapril with the doses ranging from 0.1–0.6 mg/kg/day. If nephrotic-range proteinuria was detected, corticosteroid therapy (prednisolone or intravenous methylprednisolone) was prescribed with the maximum dose of 2 mg/kg/day or not exceeding 60 mg/day. Immunosuppressive agents were also prescribed in corticosteroid-resistant cases.
Clinical outcomes were graded according to the outcome classification by Counahan27, as follows: A, normal (normal physical examination with normal urine and renal function); B, minor urinary abnormalities (proteinuria < 1 g/1.73 m2/day with or without microscopic); C, active renal disease (proteinuria > 1 g/1.73 m2/day and/or hypertension); D, renal insufficiency (eGFR < 60 mL/min/1.73 m2 or died). However, some patients who had no 24-hour urine collection at the last follow up visit, we used protein-to-creatinine ratio > 1 g/g instead of 1 g/1.73/m2/day. Outcome A or B were considered as a favorable outcome and outcome C or D were considered as an unfavorable outcome.
The IBM SPSS program version 24 was used for analysis. Data were presented as percentages, mean and standard deviation or median and interquartile range (IQR), as appropriate. Categorical data and proportions were compared using Chi-square test or Fisher’s exact test, as appropriate. Student’s t-test or Mann-Whitney U test was used for comparison of continuous data between the two groups, as appropriate. Bivariate logistic regression analysis was used to identify the factors associated with the unfavorable outcome. A p-value of less than 0.05 was considered statistically significant.