Hypoxia-Inducible Factors and Burn-Associated Acute Kidney Injury-A New Paradigm?

Dan Mircea Enescu,Maria Greabu,Silviu Constantin Badoiu,Daniela Miricescu,Iulia-Ioana Stanescu-Spinu,Alexandra Ripszky Totan,Sorin Viorel Parasca,Viorel Jinga

doi:10.3390/ijms23052470

Abstract

O2 deprivation induces stress in living cells linked to free-radical accumulation and oxidative stress (OS) development. Hypoxia is established when the overall oxygen pressure is less than 40 mmHg in cells or tissues. However, tissues and cells have different degrees of hypoxia. Hypoxia or low O2 tension may be present in both physiological (during embryonic development) and pathological circumstances (ischemia, wound healing, and cancer). Meanwhile, the kidneys are major energy-consuming organs, being second only to the heart, with an increased mitochondrial content and O2 consumption. Furthermore, hypoxia-inducible factors (HIFs) are the key players that orchestrate the mammalian response to hypoxia. HIFs adapt cells to low oxygen concentrations by regulating transcriptional programs involved in erythropoiesis, angiogenesis, and metabolism. On the other hand, one of the life-threatening complications of severe burns is acute kidney injury (AKI). The dreaded functional consequence of AKI is an acute decline in renal function. Taking all these aspects into consideration, the aim of this review is to describe the role and underline the importance of HIFs in the development of AKI in patients with severe burns, because kidney hypoxia is constant in the presence of severe burns, and HIFs are major players in the adaptative response of all tissues to hypoxia.

Highlights

In the second half of 19th century, Paul Bert was the pioneer who identified hypoxemic hypoxia as the cause of altitude sickness
Taking all these aspects into consideration, the aim of this review is to describe the role and underline the importance of hypoxia-inducible factors (HIFs) in the development of acute kidney injury (AKI) in patients with severe burns, because hypoxia of the kidneys is constant in the presence of severe burns, and HIFs are major players in the adaptative response of all tissues to hypoxia
In the presence of severe burns, one of the consequences of the post-combustion shock is represented by the centralization of the circulation with hypoxia in all tissues, excepting the heart and the brain

Summary

Introduction

In the second half of 19th century, Paul Bert was the pioneer who identified hypoxemic hypoxia as the cause of altitude sickness. HIFs adapt cells to low oxygen concentrations by regulating transcriptional programs involved in erythropoiesis, angiogenesis, and metabolism [14]. This suggests that these programs promote the growth and progression of various types of tumors. Before 1965, no patients could survive ARF caused by burns [20,25] Taking all these aspects into consideration, the aim of this review is to describe the role and underline the importance of HIFs in the development of AKI in patients with severe burns, because hypoxia of the kidneys is constant in the presence of severe burns, and HIFs are major players in the adaptative response of all tissues to hypoxia

Hypoxia-Inducible Factors

HIFs and AKI

HIFs and Mitochondria in Patients with Major Burns

HIFs and Acute Hypoxic Cell Death in Kidneys in Severe Burns

Findings

Conclusions