A systematic review of urine biomarkers in children with IgA vasculitis nephritis

Abstract

Background Nephritis is a recognised complication of IgA vasculitis (IgAV, Henoch-Schönlein purpura) contributing to 1–2% of all chronic kidney disease (CKD) stage 5. Improved understanding may reduce irreversible damage in IgAV nephritis (IgAV-N). Objective The aim of this study was to perform a comprehensive systematic literature review to identify promising clinical and pre-clinical urine biomarkers in children with IgAV-N that could predict the presence of nephritis and/or determine its severity. Methods A systematic literature review was performed using four search engines and a predefined search term strategy. Promising biomarkers were divided in terms of clinical or pre-clinical and ability to predict the presence of nephritis or determine its severity. Results were described using statistical significance (p < 0.05) and area under the curve (AUC) values. Results One hundred twenty-one studies were identified; 13 were eligible. A total of 2446 paediatric patients were included: healthy controls (n = 761), children with IgAV-N (n = 1236) and children with IgAV without nephritis (IgAV-noN, n = 449). Fifty-one percent were male, median age 7.9 years. The clinical markers, 24-h protein quantity and urine protein:creatinine ratio, were deemed acceptable for assessing severity of nephritis (AUC < 0.8). Urinary albumin concentration (Malb) performed well (AUC 0.81–0.98). The most promising pre-clinical urinary biomarkers in predicting presence of nephritis were as follows: kidney injury molecule-1 (KIM-1) (AUC 0.93), monocyte chemotactic protein-1 (MCP-1) (AUC 0.83), N-acetyl-β-glucosaminidase (NAG) (0.76–0.96), and angiotensinogen (AGT) (AUC not available). Urinary KIM-1, MCP-1, and NAG appeared to correlate with disease severity. Conclusions Longitudinal studies are needed to assess whether pre-clinical biomarkers enhance standard of care in IgAV-N.

New Insights and Challenges Associated With IgA Vasculitis and IgA Vasculitis With Nephritis—Is It Time to Change the Paradigm of the Most Common Systemic Vasculitis in Childhood?

“…Among urinary biomarkers, IgA and IgM performed best in the study conducted by Pillebout et al ( 45 ). Recent systematic review of urine biomarkers in children with IgAVN showed that the most promising urinary biomarkers in predicting nephritis were kidney injury molecule-1 (KIM-1), monocyte chemotactic protein-1 (MCP-1), N-acetyl-β-glucosaminidase (NAG), and angiotensinogen (AGT) ( 71 ). However, none of them proved yet to be an established marker of disease.…”

IgA Vasculitis: Etiology, Treatment, Biomarkers and Epigenetic Changes

“…As biomarkers for IgA nephritis, a systematic literature review was performed to predict the presence of IgA nephritis or determine its severity [ 134 ]. In urine samples, kidney injury molecule-1 (KIM-1), monocyte chemotactic protein-1 (MCP-1), and N-acetyl-β-glucosaminidase (NAG) correlate with the disease severity of nephritis.…”

IgA vasculitis in children

“…IgAV is more frequent in childhood with a peak incidence around 4-6 years of age 2,4 . The disease usually presents with a palpable purpuric rash, gastrointestinal pain and bleeding, kidney involvement, arthralgia and/or arthritis [1][2][3][4] . Testicular inflammation (orchitis: 14% of male patients) is also seen, manifested by pain and swelling 5 .…”

“…Immunoglobulin A (IgA) vasculitis (IgAV), classically known as Henoch-Schönlein purpura, is a type of non-thrombocytopenic small-vessel vasculitis and is the most frequent form of childhood systemic vasculitis (annual incidence: 3-26.7 per 100,000, depending on the country) 1 - 3 . IgAV is more frequent in childhood with a peak incidence around 4-6 years of age 2 , 4 . The disease usually presents with a palpable purpuric rash, gastrointestinal pain and bleeding, kidney involvement, arthralgia and/or arthritis 1 - 4 .Testicular inflammation (orchitis: 14% of male patients) is also seen, manifested by pain and swelling 5 .…”

“…Overall, 40-50% of affected children have kidney involvement ranging from microscopic hematuria to rapidly progressive glomerulonephritis, contributing to 1-2% of all chronic kidney disease (CKD) stage 5. 2 In adults, the disease frequently occurs with atypical clinical features, severe kidney involvement, and with unfavorable outcome 3 . Recurrence (around 1/3 of patients) is more frequent in patients with kidney involvement and its duration is usually milder or shorter than the original episode 4 .…”