Dataset Information

A new clinical multivariable model that predicts postoperative acute kidney injury: impact of endogenous ouabain.

ABSTRACT:

Background

Acute kidney injury (AKI) is an important complication of cardiac surgery. Recently, elevated levels of endogenous ouabain (EO), an adrenal stress hormone with haemodynamic and renal effects, have been associated with worse renal outcome after cardiac surgery. Our aim was to develop and evaluate a new risk model of AKI using simple preoperative clinical parameters and to investigate the utility of EO.

Methods

The primary outcome was AKI according to Acute Kidney Injury Network stage II or III. We selected the Northern New England Cardiovascular Disease Study Group (NNECDSG) as a reference model. We built a new internal predictive risk model considering common clinical variables (CLIN-RISK), compared this model with the NNECDSG model and determined whether the addition of preoperative plasma EO improved prediction of AKI.

Results

All models were tested on >800 patients admitted for elective cardiac surgery in our hospital. Seventy-nine patients developed AKI (9.9%). Preoperative EO levels were strongly associated with the incidence of AKI and clinical complication (total ICU stay and in-hospital mortality). The NNECDSG model was confirmed as a good predictor of AKI (AUC 0.74, comparable to the NNECDSG reference population). Our CLIN-RISK model had improved predictive power for AKI (AUC 0.79, CI 95% 0.73-0.84). Furthermore, addition of preoperative EO levels to both clinical models improved AUC to 0.79 and to 0.83, respectively (?AUC +0.05 and +0.04, respectively, P < 0.01).

Conclusion

In a population where the predictive power of the NNECDSG model was confirmed, CLIN-RISK was more powerful. Both clinical models were further improved by the addition of preoperative plasma EO levels. These new models provide improved predictability of the relative risk for the development of AKI following cardiac surgery and suggest that EO is a marker for renal vascular injury.

SUBMITTER: Simonini M

PROVIDER: S-EPMC4200038 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Publications

A new clinical multivariable model that predicts postoperative acute kidney injury: impact of endogenous ouabain.

Simonini Marco M Lanzani Chiara C Bignami Elena E Casamassima Nunzia N Frati Elena E Meroni Roberta R Messaggio Elisabetta E Alfieri Ottavio O Hamlyn John J Body Simon C SC Collard C David CD Zangrillo Alberto A Manunta Paolo P

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20140611 9

<h4>Background</h4>Acute kidney injury (AKI) is an important complication of cardiac surgery. Recently, elevated levels of endogenous ouabain (EO), an adrenal stress hormone with haemodynamic and renal effects, have been associated with worse renal outcome after cardiac surgery. Our aim was to develop and evaluate a new risk model of AKI using simple preoperative clinical parameters and to investigate the utility of EO.<h4>Methods</h4>The primary outcome was AKI according to Acute Kidney Injury ...[more]

PMID: 24920842

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Project description: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.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.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."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.Preoperative plasma endogenous ouabain levels are powerful biomarkers of acute kidney injury and postoperative complications and may be a direct cause of podocyte damage.

Project description:BACKGROUND:We aimed to develop a nomogram based on preprocedural features for early prediction of acute kidney injury (AKI) and to assess the prognosis in patients after radical and partial nephrectomy. METHODS:The study included a development cohort of 1111 patients who were treated between June 2012 and June 2017 and an additional validation cohort of 356 patients who were treated between July 2017 and June 2018. Stepwise regression and logistic regression analyses were used to evaluate the association between predictors and AKI. Incorporating all independent predictors, a nomogram for postoperative AKI was developed and externally validated. Patients were followed up for 5 years to assess renal function, acute kidney disease (AKD), chronic kidney disease (CKD), hospital readmission and mortality were key prognosis we focused on. RESULTS:After multivariate logistic regression, radical nephrectomy (odds ratio (OR)?=?3.57, p?<?0.001), aspirin (OR?=?1.79, p?=?0.008), systolic blood pressure (OR?=?1.41, p?=?0.004), triglyceride (OR?=?1.26, p?=?0.024), and alkaline phosphatase (OR?=?1.75, p?=?0.034) were independent risk factors for postoperative AKI, while albumin (OR?=?0.72, p?=?0.031) was a protective factor for postoperative AKI. Patients with a higher estimated glomerular filtration rate (eGFR) (60-90?ml/min/1.73?m2, OR?=?0.41, p?=?0.004; ? 90?ml/min/1.73?m2, OR?=?0.37, p?<?0.001) were less prone to AKI than those with a lower eGFR (<?15?ml/min/1.73?m2). These predictors were all included in the final nomogram. The area under the receiver operating characteristics curve for the model were 0.77 (p?<?0.001) in the development cohort and 0.72 (p?<?0.001) in the validation cohort. The incidence of AKD and CKD were 27.12 and 18.64% in AKI group, which were much higher than those in no AKI group (p?<?0.001). CONCLUSIONS:The nomogram had excellent predictive ability and might have significant clinical implications for the early detection of AKI in patients undergoing nephrectomy.

Project description:BACKGROUND AND OBJECTIVES:High BP variability may cause AKI because of inappropriate kidney perfusion. This study aimed to investigate the association between intraoperative BP variability and postoperative AKI in patients who underwent noncardiac surgery. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:We performed a cohort study of adults undergoing noncardiac surgery in hospitals in South Korea. We studied three cohorts using the following recording windows for intraoperative BP: discovery cohort, 1-minute intervals; first validation cohort, 5-minute intervals; and second validation cohort, 2-second intervals. We calculated four variability parameters (SD, coefficient of variation, variation independent of mean, and average real variability) based on the measured mean arterial pressure values. The primary outcomes were postoperative AKI (defined by the Kidney Disease Improving Global Outcomes serum creatinine cutoffs) and critical AKI (consisting of stage 2 or higher AKI and post-AKI death or dialysis within 90 days). RESULTS:In the three cohorts, 45,520, 29,704, and 7435 patients were analyzed, each with 2230 (443 critical), 1552 (444 critical), and 300 (91 critical) postoperative AKI events, respectively. In the discovery cohort, all variability parameters were significantly associated with risk of AKI, even after adjusting for intraoperative hypotension. For example, average real variability was associated with higher risks of postoperative AKI (adjusted odds ratio, 1.13 per 1 SD increment; 95% CI, 1.07 to 1.19) and critical AKI (adjusted odds ratio, 1.13 per 1 SD increment; 95% CI, 1.02 to 1.26). Associations were evident predominantly among patients who also experienced intraoperative hypotension. In the validation analysis with 5-minute-interval BP records, all four variability parameters were associated with the risk of postoperative AKI or critical AKI. In the validation cohort with 2-second-interval BP records, average real variability was the only significant variability parameter. CONCLUSIONS:Higher intraoperative BP variability is associated with higher risks of postoperative AKI after noncardiac surgery, independent of hypotension and other clinical characteristics.

Dataset Information

A new clinical multivariable model that predicts postoperative acute kidney injury: impact of endogenous ouabain.

Background

Methods

Results

Conclusion

Publications

A new clinical multivariable model that predicts postoperative acute kidney injury: impact of endogenous ouabain.

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