Effect of SGLT2 inhibitors on microscopic hematuria in IgA nephropathy: a review from the perspective of disease activity biomarkers

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Microscopic hematuria, which is thought to reflect glomerular capillary wall injury but cannot by itself distinguish active inflammation from chronic structural damage, has recently been re-recognized as an independent predictor of disease progression in IgAN, yet it has long been overlooked in the assessment of treatment response. SGLT2 inhibitors have been demonstrated to reduce proteinuria and slow the decline of kidney function in patients with IgAN and are now incorporated into first-line supportive therapy. However, existing clinical trials and guidelines have focused almost exclusively on proteinuria and estimated glomerular filtration rate (eGFR), and the effect of SGLT2 inhibitors on microscopic hematuria has not been systematically evaluated. From the perspective of disease activity biomarkers, this review summarizes the pathophysiological basis and prognostic value of hematuria in IgAN, analyzes the hemodynamic, anti-inflammatory, and cytoprotective mechanisms through which SGLT2 inhibitors may influence hematuria, critically appraises the limited clinical evidence currently available, and compares these findings with hematuria data from novel targeted therapies including anti-APRIL monoclonal antibodies and complement inhibitors. This review aims to identify a key evidence gap in the current therapeutic framework of IgAN and to frame the effect of SGLT2 inhibitors on hematuria as an important but insufficiently studied question that warrants dedicated prospective investigation.