The complex interplay between kidney injury and inflammation

Abstract

Acute kidney injury (AKI) has gained significant attention following patient safety alerts about the increased risk of harm to patients, including increased mortality and hospitalization. Common causes of AKI include hypovolaemia, nephrotoxic medications, ischaemia and acute glomerulonephritis, although in reality it may be undetermined or multifactorial. A period of inflammation either as a contributor to the kidney injury or resulting from the injury is almost universally seen. This article was compiled following a workshop exploring the interplay between injury and inflammation. AKI is characterized by some degree of renal cell death through either apoptosis or necrosis, together with a strong inflammatory response. Studies interrogating the resolution of renal inflammation identify a whole range of molecules that are upregulated and confirm that the kidneys are able to intrinsically regenerate after an episode of AKI, provided the threshold of damage is not too high. Kidneys are unable to generate new nephrons, and dysfunctional or repeated episodes will lead to further nephron loss that is ultimately associated with the development of renal fibrosis and chronic kidney disease (CKD). The AKI to CKD transition is a complex process mainly facilitated by maladaptive repair mechanisms. Early biomarkers mapping out this process would allow a personalized approach to identifying patients with AKI who are at high risk of developing fibrosis and subsequent CKD. This review article highlights this process and explains how laboratory models of renal inflammation and injury assist with understanding the underlying disease process and allow interrogation of medications aimed at targeting the mechanistic interplay.

Tetramethylpyrazine: An Active Ingredient of Chinese Herbal Medicine With Therapeutic Potential in Acute Kidney Injury and Renal Fibrosis

“…The above-mentioned damage induces the production of inflammatory mediators such as inflammatory factors, chemokines, and adhesion factors (TNF-α, TGF-β, IL-6, IL-1β, IL-18, CCL2, MCP-1, ICAM-1, and P-selectin), which help recruit leukocytes to the kidney. Neutrophils, macrophages, and lymphocytes infiltrate the injury site ( McWilliam et al, 2021 ). In addition, oxidative stress can promote inflammation, and cell damage caused by inflammation further aggravates oxidative stress ( Tucker et al, 2015 ).…”

The Density of Renal Lymphatics Correlates With Clinical Outcomes in IgA Nephropathy

“…Nevertheless, as nephron endowment is limited, and kidneys are unable to generate new nephrons, ongoing inflammation or repeated episodes of kidney injury will lead to further nephron loss that is associated with the development of cell senescence and kidney fibrosis. 20 , 21 …”

“…Moreover, misdirected tubular fluid filtration into the periglomerular space appears to enhance periglomerular fibrosis and lymphangiogenesis. 18 , 21 …”

microRNA‐486‐5p is implicated in the cisplatin‐induced apoptosis and acute inflammation response of renal tubular epithelial cells by targeting HAT1

“…The pathophysiological mechanism of cisplatin-induced AKI is extremely complicated, and the initial uncontrolled inflammation plays a harmful role in its progression. [25] Discovering effective biomarkers and studying their intrinsic molecular regulation pathways leading to kidney inflammation is one of the most promising methods AKI. [26][27][28] In this study, we found that in the injured HK-2 cell model and AKI mouse models induced by cisplatin, miR-486-5p was upregulated, whereas HAT1 was downregulated.…”