Burn-Induced Acute Kidney Injury–Two-Lane Road: From Molecular to Clinical Aspects

Abstract

Severe burn injuries lead to acute kidney injury (AKI) development, increasing the mortality risk up to 28–100%. In addition, there is an increase in hospitalization days and complications appearance. Various factors are responsible for acute or late AKI debut, like hypovolemia, important inflammatory response, excessive load of denatured proteins, sepsis, and severe organic dysfunction. The main measure to improve the prognosis of these patients is rapidly recognizing this condition and reversing the underlying events. For this reason, different renal biomarkers have been studied over the years for early identification of burn-induced AKI, like neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule-1 (KIM-1), tissue inhibitor of metalloproteinase-2 (TIMP-2), interleukin-18 (IL-18), and insulin-like growth factor-binding protein 7 (IGFBP7). The fundamental purpose of these studies is to find a way to recognize and prevent acute renal injury progression early in order to decrease the risk of mortality and chronic kidney disease (CKD) onset.

Neutrophil extracellular traps drive lupus flares with acute skin and kidney inflammation triggered by ultraviolet irradiation

“…The above results suggest that skin inflammation might be connected to kidney inflammation, with the potential communication between inflammatory cells infiltrating the skin and the kidneys, in UVB-irradiated lupus-prone mice. In line, several studies have shown that neutrophils could be potential mediators of the link between skin inflammation and kidney injury in different scenarios, including skin thermal burn and UVB irradiation (33,34). Moreover, ours and other studies have reported the role of neutrophils and/or NETosis in UVBinduced skin inflammation (15,16) or lupus kidney inflammation (18,19) in mice.…”

“…Therefore, our results suggested a potential connection between skin inflammation and kidney injury in UVB-irradiated asymptomatic lupus-prone mice. Several recent studies have demonstrated the involvement of neutrophils in linking of skin inflammation to kidney injury, observed in different settings ( 30–32 ). Previous studies from our team and others have shown the involvement of neutrophils and neutrophil NETosis in UVB-induced skin inflammation ( 15, 16 ) or lupus skin inflammation in the current study, and lupus nephritis ( 18, 19 ) in mice.…”

“…A recent study using a single highdose UVB irradiation of WT mice led to transient proteinuria, accompanied by neutrophil transmigration from the inflamed skin to the kidneys tracked by a photoactivatable lineage tracing approach (34). The above studies highlight a critical role for neutrophils in communication between the skin and kidneys, linking acute skin injury or inflammation to subsequent kidney damage (33,34). CXCR4/CXCL12 axis plays an important role in lupus pathogenesis by recruiting CXCR4-expressing immune cells, including neutrophils, into the kidneys with CXCL12 expression in patients or mice with lupus nephritis (37,42).…”

“…To explore the causality, we found that CXCR4 inhibition suppressed neutrophil infiltration to the kidneys, consequently reducing glomerular accumulation of NETs and NETassociated cytokines/C3, thereby decreasing proteinuria in UVB-irradiated lupus-prone mice. Interestingly, studies in different settings have demonstrated that either skin thermal burn in patients (33,41), or acute single high-dose UVB irradiation of WT mice (34) can induce systemic symptoms, including kidney inflammation, indicating potential dermal-renal communications in different scenarios. Over the past 60 years, numerous studies have reported proteinuria in patients with skin thermal burn (41), in which neutrophil gelatinase-associated lipocalin from activated neutrophils are implicated (33).…”

“…This closely mirrors the lupus flares associated with sunlight overexposure in humans ( 6 ). To understand the potential link between UVB-induced skin inflammation and proteinuria, we reviewed the existing literature, which has long established that patients with skin thermal burns experience proteinuria and acute kidney injury ( 29 ) with the involvement of neutrophil activation ( 30 ). A recent study with single high dose UVB irradiation of WT mice induced acute skin inflammation and transient proteinuria with neutrophil involvement in kidney injury ( 31 ).…”