Chronic kidney disease progression in glomerular diseases: is hematuria a key risk factor?

Hematuria has traditionally been considered a benign sign of glomerular injury, as reported in autosomal dominant type IV collagen-related nephropathy. However, growing clinical and experimental evidence suggests that it may be an active driver of kidney dysfunction. Persistent microscopic hematuria is associated with an increased risk of progression to kidney failure. Likewise, episodes of macroscopic hematuria, particularly in Immunoglobulin A nephropathy, can precipitate acute kidney injury and contribute to chronic impairment of kidney function. Glomerular bleeding may be associated with alterations in the glomerular filtration barrier, allowing erythrocyte leakage into the urinary space. At the molecular level, erythrocyte breakdown products, such as free hemoglobin and heme, induce oxidative stress and inflammation, exerting direct cytotoxic effects on kidney parenchymal cells. In this comprehensive review, we describe the prevalence of hematuria in pediatric patients, elucidate the cellular and molecular mechanisms by which hemoglobin and its heme derivatives promote kidney injury, evaluate the impact of hematuria on long-term kidney outcomes, and discuss emerging therapies against hematuria-induced nephrotoxicity.