AKI Associated with Macroscopic Glomerular Hematuria

Abstract

SummaryHematuria 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 hematuriaassociated 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.

Clinicopathological features and risk factors analysis of IgA nephropathy associated with acute kidney injury

“…[7][8][9] Several pathophysiologic mechanisms may account for the tubular injury found on renal biopsy specimens. 20 However, in our series, MH was only seen in 16 patients in AKI group, and we did not differentiate recurrent MH and isolated MH in this retrospective study. We found that MH was a protective factor for AKI in univariate analysis in our study.…”

Long-Term Outcome of IgA Nephropathy Patients with Recurrent Macroscopic Hematuria

“…It is important to note that an episode of MH is also associated with the incidence of acute kidney injury (AKI) [17,20,21,22,23]. The incidence of AKI after episodic MH in IgAN remains unknown; however, once it has occurred, approximately 25-27% of patients do not recover their previous renal function [20,22].…”

“…The incidence of AKI after episodic MH in IgAN remains unknown; however, once it has occurred, approximately 25-27% of patients do not recover their previous renal function [20,22]. The most frequent histological findings in MH-associated AKI are acute tubular necrosis and intraluminal obstruction by RBC or hemoglobin casts [17,20,22]. Recent studies suggested that the cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury during MH-associated AKI [20].…”

“…The most frequent histological findings in MH-associated AKI are acute tubular necrosis and intraluminal obstruction by RBC or hemoglobin casts [17,20,22]. Recent studies suggested that the cytotoxic effects of oxidative stress induced by hemoglobin, heme, or iron released from red blood cells may account for the tubular injury during MH-associated AKI [20]. Several risk factors, including a duration of MH longer than 10 days, age >50 years, decreased baseline eGFR, absence of previous episodes of MH, and the severity of tubular necrosis, were found to response for an incomplete recovery of renal function in patients with MH-associated AKI [22].…”

Methemoglobinemia-Induced Acute Kidney Injury

“…The preponderance of evidence suggests that unbound heme and free iron are involved in the pathogenesis of tubular injury observed in glomerular hematuria [14,15]. Heme is an integral component of heme proteins such as hemoglobin, myoglobin, mitochondrial cytochromes, and enzymes that regulate vascular tone, redox reactions, cell signaling, DNA transcription, and RNA translation [16].…”