Hematuria is a common finding in various glomerular diseases. This article reviews the clinical data on glomerular
hematuria and kidney injury, as well as the pathophysiology of hematuria-associated renal damage. Although
glomerular hematuria has been considered a clinical manifestation of glomerular diseases without real
consequences on renal function and long-term prognosis, many studies performed have shown a relationship
between macroscopic glomerular hematuria and AKI and have suggested that macroscopic hematuria-associated
AKI is related to adverse long-term outcomes. Thus, up to 25% of patients with macroscopic hematuria–
associated AKI do not recover baseline renal function. Oral anticoagulation has been associated with glomerular
macrohematuria–related kidney injury. Several pathophysiologic mechanisms may account for the tubular injury
found on renal biopsy specimens. Mechanical obstruction by red blood cell casts was thought to play a role. More
recent evidence points to cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from
red blood cells. These mechanisms of injury may be shared with hemoglobinuria or myoglobinuria-induced AKI.
Heme oxygenase catalyzes the conversion of heme to biliverdin and is protective in animal models of heme
toxicity. CD163, the recently identified scavenger receptor for extracellular hemoglobin, promotes the activation
of anti-inflammatory pathways, opening the gates for novel therapeutic approachesThis work was supported by FIS (Programa Miguel Servet)
to J.A.M.; ISCIII and FEDER funds CP04/00060, PS09/00447,
Sociedad Espa~nola de Nefrologia, ISCIII-RETIC REDinREN/RD06/
0016, Comunidad de Madrid/FRACM/S-BIO0283/2006, Programa
Intensificación Actividad Investigadora (ISCIII/) to A.O.; FIS 10/
02668 and AITER (Asociación para el Estudio y Tratamiento de las
Enfermedades Renales) to E.G. and M.P.; and ISCIII-Redes
RECAVA (RD06/0014/0035) and ISCIII funds PI10/00072 and
Fundacion Lilly to J.E
