Integrative View of the Mechanisms that Induce Acute Kidney Injury and its Transition to Chronic Kidney Disease

Abstract

There is ample evidence showing that acute kidney injury (AKI) increases the risk of developing chronic kidney disease (CKD).Although considerable efforts have been undertaken in recent years to elucidate the mechanisms responsible for the AKI to CKD transition, many questions remain to be answered. In this review, we address most of the latest studies elucidating the mechanisms involved in this transition. Based on recent studies, the consensus to date is that endothelial and proximal tubular epithelium injury along with the activation of inflammatory processes occurring after an AKI episode, not only establish a close interrelation but also trigger a series of signaling pathways that culminate in the generation of tubulointerstitial fibrosis and chronic hypoxia, which lead to the progressive deterioration of functional tissue. These events highlight that the tubular epithelium does not appear to be the same after cell damage occurs. In this review, we present the advances aimed at elucidating the mechanisms that lead to a maladaptive response and how sex hormones seem to be involved in a positive or negative adaptive response. Elucidating and characterizing the mechanisms responsible for the AKI to CKD transition are an indispensable preliminary step that will help to identify the most important actors in this process. (REV INVEST CLIN. 2018;70:261-8)

Catechins: Therapeutic Perspectives in COVID-19-Associated Acute Kidney Injury

“…According to studies discussed in this review, these natural products exhibit significant nephroprotective effects in blocking or attenuating renal dysfunctions and glomerulus/tubular lesions caused by varied nephrotoxic origins [ 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 ]. Even though more studies are needed to elucidate the mechanisms underlying nephroprotective effects of catechins, the renoprotection promoted by catechins appears to be strongly associated with their antioxidant, anti-inflammatory and anti-apoptotic activities into renal tissues [ 100 , 101 ]. Among the catechins discussed, ECGC is a very promising nephroprotective and anti-SARS-CoV-2 compound, especially due to the antiviral activities discussed earlier in this review [ 67 , 68 , 69 ].…”

“…In general, the mechanisms underlying nephrotoxicity are: (a) kidney-specific mitochondrial oxidative stress, caused by altered activities of mitochondrial electron transport chain enzyme complexes and accompanied by impaired antioxidant defenses, (b) inflammation, as evidenced by elevated levels of inflammatory mediators, such as TNF-α, IL-1, increased activities of NF-κB and p53 induction, and (c) apoptotic cell death, as indicated by high caspase-3 activity and DNA fragmentation in diverse clinical and experimental studies of AKI [ 100 , 101 ]. Oxidative stress is an important risk factor for AKI, as evidenced by a decrease in antioxidant enzymes’ activities, an increase in lipid peroxidation and elevated levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in AKI induced by nephrotoxic drugs and obstructive nephropathies [ 52 , 53 , 54 , 55 ].…”

Understanding the opposite effects of sex hormones in mediating renal injury

“…The endothelium contributes to the maintenance of tone and vascular permeability, both of which are affected during an AKI episode and lead to alterations in vasoactive molecules release, such as nitric oxide (NO), endothelin and angiotensin II (Ang II) 11,12 . Nitric oxide plays an important role in regulating renal vascular tone by maintaining a state of vasodilation.…”

Reduced endothelial nitric oxide synthase activation contributes to cardiovascular injury during chronic kidney disease progression

“…Indeed, the proteinuria, fibrosis, and increased oxidative stress were not significantly ameliorated by L-arginine administration in AKI-CKD rats. The lack of protective kidney effect of L-arginine might be due to the multiple mechanisms that participate in the AKI to CKD transition, including chronic inflammation, capillary rar-efaction, tubular cell arrest in the G 2 /M phase, and pericyte detachment and differentiation into myofibroblasts (16). However, we observed a positive effect of L-arginine on renal blood flow and creatinine clearance that can be possibly explained by a direct effect on the kidney vasculature tone and renal perfusion.…”