Molecular Mechanisms of Kidney Injury and Repair

Abstract

Chronic kidney disease (CKD) will become the fifth global cause of death by 2040, thus emphasizing the need to better understand the molecular mechanisms of damage and regeneration in the kidney. CKD predisposes to acute kidney injury (AKI) which, in turn, promotes CKD progression. This implies that CKD or the AKI-to-CKD transition are associated with dysfunctional kidney repair mechanisms. Current therapeutic options slow CKD progression but fail to treat or accelerate recovery from AKI and are unable to promote kidney regeneration. Unraveling the cellular and molecular mechanisms involved in kidney injury and repair, including the failure of this process, may provide novel biomarkers and therapeutic tools. We now review the contribution of different molecular and cellular events to the AKI-to-CKD transition, focusing on the role of macrophages in kidney injury, the different forms of regulated cell death and necroinflammation, cellular senescence and the senescence-associated secretory phenotype (SAPS), polyploidization, and podocyte injury and activation of parietal epithelial cells. Next, we discuss key contributors to repair of kidney injury and opportunities for their therapeutic manipulation, with a focus on resident renal progenitor cells, stem cells and their reparative secretome, certain macrophage subphenotypes within the M2 phenotype and senescent cell clearance.

Metabolomic Analysis of Stephania tetrandra–Astragalus membranaceus Herbal Pair-Improving Nephrotic Syndrome Identifies Activation of IL-13/STAT6 Signaling Pathway

“…Abnormal expression of proinflammatory cytokines, such as IL-6 and TNF-α, in the kidney recruits associated inflammatory cells and causes inflammation in the kidney tissue. In addition, pro-inflammatory cytokines can trigger cell apoptosis and promote the synthesis of other inflammatory molecules, thus causing inflammatory response [ 23 ]. Apoptosis leads to the loss of resident kidney cells and subsequent renal injury induced by environmental and intrinsic stimuli.…”

Tissue-specific cells generated to predict xenogeneic immune responses demonstrate that SLA-downregulated kidney proximal tubular epithelial cells are low immunogenic

“…Furthermore, to evaluate if SV40 T-ag expression affects PTEC functionality, we tested their capacity to migrate. Previous studies have shown that epithelial cells, especially after injury, exhibit a high capacity for tissue repair and regeneration compared to their healthy state in which they are mitotically quiescent 11,12 . In the kidney, this repair function is not provided by identi able stem cell populations as compared to organs with high rates of cell turnover.…”

Gender and Renal Insufficiency: Opportunities for Their Therapeutic Management?

“…However, the severity of the acute episode is not the only determinant of the progression of kidney damage. It is believed that the age of the affected person may also be important, especially in the processes of survival and resistance of kidney cells as well as the resumption of normal activity [ 40 ]. The most acute damage in kidney cells occurs in the tubular epithelial cells of the proximal S3 segment of the outer cord stripe.…”