Preprint Review Version 1 This version is not peer-reviewed

Pigment Nephropathy: Novel Insights into Inflammasome-Mediated Pathogenesis

Version 1 : Received: 17 April 2019 / Approved: 18 April 2019 / Online: 18 April 2019 (08:11:08 CEST)

A peer-reviewed article of this Preprint also exists.

Giuliani, K.T.K.; Kassianos, A.J.; Healy, H.; Gois, P.H.F. Pigment Nephropathy: Novel Insights into Inflammasome-Mediated Pathogenesis. Int. J. Mol. Sci. 2019, 20, 1997. Giuliani, K.T.K.; Kassianos, A.J.; Healy, H.; Gois, P.H.F. Pigment Nephropathy: Novel Insights into Inflammasome-Mediated Pathogenesis. Int. J. Mol. Sci. 2019, 20, 1997.

Journal reference: Int. J. Mol. Sci. 2019, 20, 1997
DOI: 10.3390/ijms20081997

Abstract

Pigment nephropathy is an acute decline in renal function following the deposition of endogenous haem-containing proteins in the kidneys. Haem pigments such as myoglobin and haemoglobin are filtered by glomeruli and absorbed by the proximal tubules. They cause renal vasoconstriction, tubular obstruction, increased oxidative stress and inflammation. Haem is associated with inflammation in sterile and infectious conditions, contributing to the pathogenesis of many disorders such as rhabdomyolysis and haemolytic diseases. In fact, haem appears to be a signaling molecule that is able to activate the inflammasome pathway. Recent studies highlight a pathogenic function for haem in triggering inflammatory responses through the activation of the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome. Among the inflammasome multiprotein complexes, the NLRP3 inflammasome has been the most widely characterized as a trigger of inflammatory caspases and the maturation of interleukin-18 and -1β. In the present review, we discuss the latest evidence on the importance of inflammasome-mediated inflammation in pigment nephropathy. Finally, we highlight the potential role of inflammasome inhibitors in the prophylaxis and treatment of pigment nephropathy.

Subject Areas

rhabdomyolysis; pigment nephropathy; haem; NLRP3 inflammasome; acute kidney injury

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