Abstract
With iron at its core, the tetrapyrrole heme ring is a cardinal prosthetic group made up of many proteins that participate in a wide array of cellular functions and metabolism. Once released, due to its pro-oxidant properties, free heme in sufficient amounts can result in injurious effects to the kidney and other organs. Heme oxygenase-1 (HO-1) has evolved to promptly attend to such injurious potential by facilitating degradation of heme into equimolar amounts of carbon monoxide, iron, and biliverdin. HO-1 induction is a beneficial response to tissue injury in diverse animal models of diseases, including those that affect the kidney. These protective attributes are mainly due to: (i) prompt degradation of heme leading to restraining potential hazardous effects of free heme, and (ii) generation of byproducts that along with induction of ferritin have proven beneficial in a number of pathological conditions. This review will focus on describing clinical aspects of some of the conditions with the unifying end-result of increased heme burden and will discuss the molecular mechanisms that ensue to protect the kidneys.
Highlights
Heme is an evolutionarily conserved, ubiquitous iron-containing compound that is essential in numerous cellular functions [1,2,3]
While the precise mechanisms that culminate in the pathogenesis of malaria-induced kidney disease are not fully described, multiple pathways and mechanisms have been demonstrated to have fundamental significance in this context
This study demonstrated how macrophages contribute to the pathogenesis of rhabdomyolysis by releasing extracellular traps that are comprised of DNA fibers and granule proteins
Summary
Heme is an evolutionarily conserved, ubiquitous iron-containing compound that is essential in numerous cellular functions [1,2,3]. During pathological conditions and upon injury, heme can be released and when present in sufficient amount leads to commencement of an injury cycle that could eventually lead to cellular death and organ failure [2] As it pertains to the kidney, several clinical conditions have been recognized that are associated with significant amount of free heme and subsequent kidney damage [5,6,7]. The list of such clinical settings is vast and includes some frequent diseases and syndromes, massive intravascular hemolysis and rhabdomyolysis are the main culprits that may result in diverse forms of kidney disease, most commonly acute kidney injury (AKI) [5] Both myoglobin and hemoglobin are filtered by the glomerulus into the urinary space where they are degraded, releasing heme pigment. Within the limitation of the review, we will only discuss some of the most common conditions associated with increased heme burden from a clinical perspective and will follow that with brief description of the literature about current understanding of the molecular mechanisms that confer protection against heme mediated toxicity and organ damage
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