title: AKI associated with macroscopic glomerular hematuria: clinical and pathophysiologic consequences.
abstract: 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 approaches.
authors.affiliation: Division of Nephrology and Hypertension, IIS-Fundación Jiménez Díaz, Autonoma University, Madrid, Spain.
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Moreno
authors.forename: Catalina
authors.initials: C
authors.lastname: Martín-Cleary
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gutiérrez
authors.forename: Oscar
authors.initials: O
authors.lastname: Toldos
authors.forename: Luis Miguel
authors.initials: LM
authors.lastname: Blanco-Colio
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.forename: Alberto
authors.initials: A
authors.lastname: Ortiz
authors.forename: Jesús
authors.initials: J
authors.lastname: Egido
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology*; D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects; D005922:Glomerulonephritis, IGA / Q000150:complications; D006417:Hematuria / Q000150:complications*; D006418:Heme / Q000633:toxicity; D006456:Hemoglobinuria / Q000150:complications; D006801:Humans
chemical_list: D000925:Anticoagulants; D006418:Heme