Document Detail

Preoperative endogenous ouabain predicts acute kidney injury in cardiac surgery patients.
MedLine Citation:
PMID:  23314581     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: 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.
RATIONALE AND DESIGN: 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.
PATIENTS: 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."
MAIN 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.
Elena Bignami; Nunzia Casamassima; Elena Frati; Chiara Lanzani; Laura Corno; Ottavio Alfieri; Stephen Gottlieb; Marco Simonini; Keyur B Shah; Anna Mizzi; Elisabetta Messaggio; Alberto Zangrillo; Mara Ferrandi; Patrizia Ferrari; Giuseppe Bianchi; John M Hamlyn; Paolo Manunta
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Validation Studies    
Journal Detail:
Title:  Critical care medicine     Volume:  41     ISSN:  1530-0293     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-21     Completed Date:  2013-04-16     Revised Date:  2013-09-10    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  744-55     Citation Subset:  AIM; IM    
Anesthesia and Intensive Care Unit, San Raffaele Scientific Institute, University Vita Salute San Raffaele, Milan, Italy.
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MeSH Terms
Acute Kidney Injury / diagnosis,  etiology*
Biological Markers / blood
Coronary Artery Bypass*
Heart Valves / surgery*
Middle Aged
Models, Animal
Ouabain / blood*
Postoperative Complications / diagnosis
Predictive Value of Tests
Preoperative Period
Prospective Studies
Rats, Sprague-Dawley
Grant Support
Reg. No./Substance:
0/Biological Markers; 630-60-4/Ouabain
Comment In:
Crit Care Med. 2013 Jul;41(7):e141   [PMID:  23774366 ]
Crit Care Med. 2013 Jul;41(7):e140-1   [PMID:  23774365 ]
Crit Care Med. 2013 Mar;41(3):914-5   [PMID:  23425825 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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