Adverse effects of the renal accumulation of haem proteins. Novel therapeutic approaches

Abstract

Haemoglobin and myoglobin are haem proteins that play a key role as they help transport oxygen around the body. However, because of their chemical structure, these molecules can exert harmful effects when they are released massively into the bloodstream, as reported in certain pathological conditions associated with rhabdomyolysis or intravascular haemolysis. Once in the plasma, these haem proteins can be filtered and can accumulate in the kidney, where they become cytotoxic, particularly for the tubular epithelium, inducing acute kidney failure and chronic kidney disease. In this review, we will analyse the different pathological contexts that lead to the renal accumulation of these haem proteins, their relation to both acute and chronic loss of renal function, the pathophysiological mechanisms that cause adverse effects and the defence systems that counteract such actions. Finally, we will describe the different treatments currently used and present new therapeutic options based on the identification of new cellular and molecular targets, with particular emphasis on the numerous clinical trials that are currently ongoing.

Keywords: Acute kidney failure; Chronic kidney disease; Enfermedad renal crónica; Fracaso renal agudo; Haematuria; Haemoglobin; Haemoglobinuria; Hematuria; Hemoglobina; Hemoglobinuria; Mioglobina; Myoglobin; Rabdomiólisis; Rhabdomyolysis.