Microscopic hematuria in IgA nephropathy: a biomarker of disease activity

Immunoglobulin A nephropathy (IgAN) is an immune-mediated disease of B-cell origin and the most common primary glomerulonephritis worldwide, which often progresses to kidney failure within 10-20 years of diagnosis. Microscopic hematuria is frequently observed in IgAN; it is thought to result from damage to the glomerular filtration barrier caused by pathogenic immune complex deposits, allowing red blood cells to leak into the urinary space. Emerging evidence suggests that microscopic hematuria in IgAN may be linked to active glomerular inflammation, poorer disease prognosis and progressive kidney function decline. Despite this, it remains an underutilized biomarker for IgAN because of a lack of standardization (which can lead to preanalytical errors), challenging logistical considerations in large multicenter trials and non-glomerular hematuria as a confounding factor. The "proteinuria-centric" approach by the nephrology community may overlook that active forms of glomerulonephritis manifest with both proteinuria and hematuria, in contrast to primary podocytopathies where proteinuria is the main feature. When properly assessed, microscopic hematuria is a prognostically relevant biomarker in IgAN that may improve risk stratification and assessment of therapeutic response when evaluated alongside traditional biomarkers. This review evaluates the methods of assessment, pathophysiology and clinical utility of microscopic hematuria in IgAN.