title: Preoperative endogenous ouabain predicts acute kidney injury in cardiac surgery patients.
abstract: OBJECTIVE
  Acute kidney injury is a frequent complication of cardiac surgery and increases morbidity and mortality. As preoperative biomarkers predicting the development of acute kidney injury are not available, we have tested the hypothesis that preoperative plasma levels of endogenous ouabain may function as this type of biomarker.
  
  
  METHODS
  Endogenous ouabain is an adrenal stress hormone associated with adverse cardiovascular outcomes. Its involvement in acute kidney injury is unknown. With studies in patients and animal settings, including isolated podocytes, we tested the above mentioned hypothesis.
  
  
  METHODS
  Preoperative endogenous ouabain was measured in 407 patients admitted for elective cardiac surgery and in a validation population of 219 other patients. We also studied the effect of prolonged elevations of circulating exogenous ouabain on renal parameters in rats and the influence of ouabain on podocyte proteins both "in vivo" and "in vitro."
  
  
  RESULTS
  In the first group of patients, acute kidney injury (2.8%, 8.3%, 20.3%, p < 0.001) and ICU stay (1.4±0.38, 1.7±0.41, 2.4±0.59 days, p = 0.014) increased with each incremental preoperative endogenous ouabain tertile. In a linear regression analysis, the circulating endogenous ouabain value before surgery was the strongest predictor of acute kidney injury. In the validation cohort, acute kidney injury (0%, 5.9%, 8.2%, p < 0.0001) and ICU stay (1.2±0.09, 1.4±0.23, 2.2±0.77 days, p = 0.003) increased with the preoperative endogenous ouabain tertile. Values for preoperative endogenous ouabain significantly improved (area under curve: 0.85) risk prediction over the clinical score alone as measured by integrate discrimination improvement and net reclassification improvement. Finally, in the rat model, elevated circulating ouabain reduced creatinine clearance (-18%, p < 0.05), increased urinary protein excretion (+ 54%, p < 0.05), and reduced expression of podocyte nephrin (-29%, p < 0.01). This last finding was replicated ex vivo by incubating podocyte primary cell cultures with low-dose ouabain.
  
  
  CONCLUSIONS
  Preoperative plasma endogenous ouabain levels are powerful biomarkers of acute kidney injury and postoperative complications and may be a direct cause of podocyte damage.
authors: Anesthesia and Intensive Care Unit, San Raffaele Scientific Institute, University Vita Salute San Raffaele, Milan, Italy.
authors: Elena
authors: E
authors: Bignami
authors: Nunzia
authors: N
authors: Casamassima
authors: Elena
authors: E
authors: Frati
authors: Chiara
authors: C
authors: Lanzani
authors: Laura
authors: L
authors: Corno
authors: Ottavio
authors: O
authors: Alfieri
authors: Stephen
authors: S
authors: Gottlieb
authors: Marco
authors: M
authors: Simonini
authors: Keyur B
authors: KB
authors: Shah
authors: Anna
authors: A
authors: Mizzi
authors: Elisabetta
authors: E
authors: Messaggio
authors: Alberto
authors: A
authors: Zangrillo
authors: Mara
authors: M
authors: Ferrandi
authors: Patrizia
authors: P
authors: Ferrari
authors: Giuseppe
authors: G
authors: Bianchi
authors: John M
authors: JM
authors: Hamlyn
authors: Paolo
authors: P
authors: Manunta
mesh_terms: D058186:Acute Kidney Injury / Q000175:diagnosis / Q000209:etiology*; D000328:Adult; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001026:Coronary Artery Bypass; D005260:Female; D006351:Heart Valves / Q000601:surgery*; D006801:Humans; D008297:Male; D008875:Middle Aged; D023421:Models, Animal; D010042:Ouabain / Q000097:blood*; D011183:Postoperative Complications / Q000175:diagnosis; D011237:Predictive Value of Tests; D057234:Preoperative Period; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D010042:Ouabain