Molecular Mechanisms of AKI in the Elderly: From Animal Models to Therapeutic Intervention

Abstract

Acute kidney injury (AKI), a critical syndrome characterized by a sudden reduction of renal function, is a common disorder among elderly patients particularly in Intensive Care Unit (ICU). AKI is closely associated with both short- and long-term mortality and length of hospital stay and is considered a predictor of chronic kidney disease (CKD). Specific hemodynamic, metabolic, and molecular changes lead to increased susceptibility to injury in the aged kidney; therefore, certain causes of AKI such as the prerenal reduction in renal perfusion or vascular obstructive conditions are more common in the elderly; moreover, AKI is often multifactorial and iatrogenic. Older patients present several comorbidities (diabetes, hypertension, heart failure) and are exposed to multiple medical interventions such as the use of nephrotoxic contrasts media and medications, which can also trigger AKI. Considering the emerging relevance of this condition, prevention and treatment of AKI in the elderly should be crucial in the internist and emergency setting. This review article summarizes the incidence, the risk factors, the pathophysiology, the molecular mechanisms and the strategies of prevention and treatment of AKI in elderly patients.

Nomogram to predict the risk of acute kidney injury in patients with diabetic ketoacidosis: an analysis of the MIMIC-III database

“…Early antihypertensive therapy may further reduce renal perfusion and worsened renal outcome after AKI [28]. The decrease in blood pressure is a manifestation of hypovolemia, and SBP and DBP were significantly decreased in both groups of patients in this study cohort, which is in accord with the pathophysiological mechanism of DKA-capacity depletion due to dehydration [29,30]. However there was no significant difference in SBP between the two groups, and DBP was significantly lower in the AKI group.…”

Autophagosome protects proximal tubular cells from aldosterone-induced senescence through improving oxidative stress

“…Infusion of Aldo contributed to senescence, apoptosis, and tubulointerstitial fibrosis both in vivo and in vitro [27]. Furthermore, cells would move toward senescence, dedifferentiate into other phenotypes, and ultimately undergo apoptosis when excessive stress cannot be managed by the endogenous repair system [2,[28][29][30]. Thus, improving senescence at the early stage of Aldo-induced PTC injury is a potential intervene target.…”

Cellular senescence, a novel therapeutic target for mesenchymal stem cells in acute kidney injury

“…However, if abnormally activated, it leads to reduced proliferative capacity, persistent inflammation and formation of fibrosis, similar to the pathophysiological changes during maladaptive repair after AKI, indicating that the reduced regenerative capacity after AKI‐induced cell injury was associated with the uncontrolled cellular senescence machinery 8‐10 . In the context of AKI, registry data have also demonstrated that the incidence of AKI was much higher in CKD patients and healthy elderly population, who presented with a high background level of cellular senescence 11,12 . These examples implicate a proof‐of‐concept relationship between post‐insult cellular senescence and a poor fibrotic outcome of AKI.…”

“…[8][9][10] In the context of AKI, registry data have also demonstrated that the incidence of AKI was much higher in CKD patients and healthy elderly population, who presented with a high background level of cellular senescence. 11,12 These examples implicate a proof-of-concept relationship between post-insult cellular senescence and a poor fibrotic outcome of AKI. Complemented by a recent finding that selective elimination of senescent cells in mice significantly extended their healthy lifespan and alleviated physical dysfunction, it could be assumed that cellular senescence could become a novel target for the treatment of AKI, and re-balancing its homoeostasis has potential benefits.…”