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Syndecan-1 may predict kidney injury after ped heart surgery

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Syndecan-1 may have its flaws

Results of AKI in heart surgery patients have been “sobering,” with up to 56% of these patients being diagnosed with AKI, but research such as that by Dr. Cavalcante and colleagues represents a new approach to improving outcomes by combining clinical risk factors with specific biomarkers to identify patients at risk, Petros V. Anagnostopoulos, MD, of American Family Children’s Hospital, University of Wisconsin, said in his invited commentary (J Thorac Cardiovasc Surg. 2016;152[1]:187-8).

Dr. Anagnostopoulos acknowledged problems with traditional markers for renal function. “An ideal biomarker should be sensitive, easy to measure, reproducible, and inexpensive,” he said. “Finally, when combined with clinical prediction models, it should potentiate the discrimination of these models.”

Syndecan-1 answers that call, he said. “It peaks early and is cheap, fast, and easy to measure with readily available methods, which makes it an ideal early biomarker of AKI,” Dr. Anagnostopoulos said. Even so, he pointed out potential shortcomings of syndecan-1: It is not renal specific and it does not increase before the operation.

But he applauded Dr. Cavalcante and colleagues for pursuing research to combine clinical risk factors with specific biomarkers. “It is very likely that this type of clinical research will become prevalent in the near future and will hopefully produce results that will allow better individual patient-specific risk stratification,” Dr. Anagnostopoulos said.

He had no financial relationships to disclose.


 

FROM THE JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY

References

Acute kidney injury is a common complication after pediatric cardiac surgery, but measuring for a specific genetic protein immediately after cardiac surgery may improve cardiac surgeons’ ability to predict patients at higher risk of AKI, according to researchers from Brazil. The study results are in the July issue of the Journal of Thoracic and Cardiovascular Surgery (2016;152-178-86).

“Plasma syndecan-1 levels measured early in the postoperative period were independently associated with severe acute kidney injury,” wrote Candice Torres de Melo Bezerra Cavalcante, MD, of Heart Hospital of Messejana and Federal University of Ceará.

Their prospective cohort study involved 289 pediatric patients who had cardiac surgery at their institution between September 2013 and December 2014.

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Dr. Cavalcante and colleagues acknowledged that the traditional biomarker for renal function, serum creatinine, only increases appreciably after the glomerular filtration rate declines 50%, impairing physicians’ ability to detect AKI early enough to treat it. “This delay can explain, in part the, negative results in AKI therapeutic clinical trials,” they wrote.

They evaluated two different endothelial biomarkers in addition to syndecan-1 with regard to their capacity for predicting severe AKI: plasma ICAM-1, a marker of endothelial cell activation; and E-selectin, an endothelial cell adhesion molecule. Syndecan-1 works as a biomarker of injury to the glycocalyx protein that surrounds endothelial cell membranes that acts as a permeability barrier and prevents the cells from adhering to blood. They found that median syndecan-1 levels soon after surgery were higher in patients with severe AKI, 103.6 vs. 42.3 ng/mL.

“Although syndecan-1 is not a renal-specific biomarker, there has been recent increasing evidence that endothelial injury has an important role in AKI pathophysiology,” the researchers noted.

Study results showed the higher the level of syndecan-1, the greater the adjusted odds ratio (OR) for severe AKI. Levels of less than 17 ng/mL were considered normal; 17.1-46.7 ng/mL carried an adjusted OR of 1.42; 47.4-93.1 ng/mL had an adjusted OR of 2.05; and levels 96.3 or greater had an OR of 8.87.

“Maintenance of endothelial glycocalyx integrity can be a therapeutic target to reduce AKI in this setting,” the researchers wrote.

The authors acknowledged that the study was done at a single center that had dialysis and death rates three and five times higher, respectively, than those of developed countries; and it measured syndecan-1 at only one time point almost immediately after the operation.

“Adding postoperative syndecan-1, even when using a clinical model that already incorporates variables from renal angina index, results in significant improvement in the capacity to predict severe AKI,” Dr. Cavalcante and colleagues concluded.

They had no financial relationships to disclose.

cardnews@frontlinemedcom.com

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