Raw and salt-processed Achyranthes bidentata attenuate LPS-induced acute kidney injury by inhibiting ROS and apoptosis via an estrogen-like pathway

Current reports on acute kidney injury (AKI) in the intensive care unit (ICU) show wide variation in occurrence rate and are limited by study biases such as use of incomplete AKI definition, selected cohorts, or retrospective design. Our aim was to prospectively investigate the occurrence and outcomes of AKI in ICU patients.

AKI is pathologically characterized by sublethal and lethal damage of renal tubules. Under these conditions, renal tubular cell death may occur by regulated necrosis (RN) or apoptosis. In the last two decades, tubular apoptosis has been shown in preclinical models and some clinical samples from patients with AKI. Mechanistically, apoptotic cell death in AKI may result from well described extrinsic and intrinsic pathways as well as ER stress. Central converging nodes of these pathways are mitochondria, which become fragmented and sensitized to membrane permeabilization in response to cellular stress, resulting in the release of cell death-inducing factors. Whereas apoptosis is known to be regulated, tubular necrosis was thought to occur by accident until recent work unveiled several RN subroutines, most prominently receptor-interacting protein kinase-dependent necroptosis and RN induced by mitochondrial permeability transition. Additionally, other cell death pathways, like pyroptosis and ferroptosis, may also be of pathophysiologic relevance in AKI. Combination therapy targeting multiple cell-death pathways may, therefore, provide maximal therapeutic benefits.

The Acute Dialysis Quality Initiative Working Group recently developed the RIFLE criteria, a consensus definition for acute kidney injury (AKI). We sought to evaluate the RIFLE criteria on the day of ICU admission in a large heterogenous population of critically ill patients. Retrospective interrogation of prospectively collected data from the Australian New Zealand Intensive Care Society Adult Patient Database. We evaluated 120 123 patients admitted for >/=24 h from 1 January 2000 to 31 December 2005 from 57 ICUs across Australia. The median (IQR) age was 64.3 (50.8-75.4) years, 59.5% were male, 28.6% had co-morbid disease, 50.3% were medical admissions and the initial mean (+/-SD) APACHEII score was 16.9 (+/-7.7). According to the RIFLE criteria, on the day of admission, AKI occurred in 36.1%, with a maximum RIFLE category of Risk in 16.3%, Injury in 13.6%, and Failure 6.3%. AKI, defined by any RIFLE category, was associated with an increase in hospital mortality (OR 3.29, 95% CI 3.19-3.41, P 36% with AKI on the day of admission. For successive increases in severity of RIFLE category, there were increases in hospital mortality. The RIFLE criteria represent a simple tool for the detection and classification of AKI and for correlation with clinical outcomes.