Skip to main content

Table 1 Hallmarks and causes defining AKI

From: A combinatorial approach of Proteomics and Systems Biology in unravelling the mechanisms of acute kidney injury (AKI): involvement of NMDA receptor GRIN1 in murine AKI

Event Modulated associated event Modulation in AKI Molecular cause
RAAS activation Angiotensin signalling up Cathepsin/kallikrein/kininogen activity, blood pressure, pH
Vasoconstriction Vasoconstrictors (endothelin, angiotensin, MMP2) up RAAS pathway induction, endothelial obstruction
  Vasodilators (NO) down NOS inhibition, reduced NO bioavailability by ROS activity
Hyperglycaemia   up 20-hydroxyeicosatetraenoic acid (20-HETE), Glycogen phosphorylase, PPARγ
Elevated blood pressure Hypertension up Renin, 20-hydroxyeicosatetraenoic acid (20-HETE), mineralocorticoid receptor
Hypoxia HIF1α up Induction by vasoconstriction and ECM accumulation
  NADPH oxidases up Induction by RAAS and PLCβ
  ROS levels up NAD(P)H oxidases, P450 isoforms, Xanthine dehydrogenase
  NFκB activity up ROS-modulated activation
  Inflammation factors (TNFα, TF, PAT1, MCP1) up NFκB-mediated gene expression
  Inflammation and inflammatory response up JAK/STAT- and NFκB-dependent gene activation, other pathways
  Atherogenesis, fibrinogenesis up TGFβ signalling and gene activation pathway
  ATP levels down Depletion by PMCA activity and others, and inhibition of de-novo ATP production
  NAD levels down Rundown by PARP
  Hypoxanthine levels up Metabolic shift from accumulated XMP, IMP and Inosine
  Necrosis up ROS, SOD, OH., DNA damage, PARP, NAD rundown
PI3K modulation PI3Kinase activity down Inhibition by Jnk and PKCα
  Insulin signalling down Inhibition by RAAS and PPARγ systems
Accumulation of free and esterified cholesterol Systemic stress response up LIPE inhibition by PP1
Na+/Cl- retention, increased luminal Na+ Aldosterone/cortisol signalling events up Mineralocorticoid/Glucocorticoid-receptors, acting on Na+/Cl- pumps
Ras activation Ras signalling up Mineralocorticoid/Glucocorticoid-receptor-dependent gene activation, Angiotensin receptor signalling
Cytoskeletal reorganization ECM remodelling up Hsp27, ATP depletion, Rac1 activation, Ras mediated events
Tubular cell dynamics Infiltration of immature cells up Pro-apoptotic signals
  1. Clinical and disease model observations were analysed based on modulated associated events, directionality in terms of in- or decrease, and plausible molecular causes.