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Protective effect of soluble Klotho in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass
Naomi Pode Shakked1,2,3, Orgad Rosenblat1,4, Doron Sagiv1,3,5
1Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Insights
Serum Klotho levels significantly decrease after pediatric cardiac surgery with cardiopulmonary bypass (CPB). Lower Klotho levels post-surgery predict a higher risk of complications in children with congenital heart defects (CHDs).
Area of Science:
- Biochemistry
- Pediatric Cardiology
- Surgical Outcomes
Background:
- Klotho protein, particularly soluble Klotho, is recognized for its antiaging properties and protective effects on renal and cardiovascular systems.
- Cardiopulmonary bypass (CPB) during cardiac surgery is associated with adverse outcomes in both pediatric and adult populations.
- Congenital heart defects (CHDs) often require surgical intervention involving CPB, necessitating methods to predict patient outcomes.
Purpose of the Study:
- To investigate the dynamic changes in serum Klotho levels in pediatric patients undergoing cardiac surgery with CPB.
- To determine if serum Klotho levels can serve as a predictive biomarker for postoperative complications in children with CHDs.
- To assess the association between Klotho levels and various clinical parameters in this patient cohort.
Main Methods:
- A prospective study involving 29 pediatric patients with CHDs undergoing corrective surgery with CPB.
- Serum samples were collected at baseline, and 2, 6, and 24 hours post-surgery.
- Soluble Klotho levels were quantified using enzyme-linked immunosorbent assay (ELISA).
Main Results:
- Serum Klotho levels significantly decreased 2 hours after CPB, returning to baseline by 6 hours (p < .001 and p < .05, respectively).
- Patients with low Klotho levels at 2 hours post-surgery exhibited a 32-fold increased risk of developing postoperative complications (p = .015).
- Consistently lower Klotho levels were observed across all time points in patients who experienced postoperative complications.
Conclusions:
- Cardiac surgery utilizing CPB leads to a significant, albeit temporary, reduction in serum Klotho levels in pediatric patients with CHDs.
- Postoperative serum Klotho levels, particularly at the 2-hour mark, are a valuable predictor of adverse outcomes and complications.
- Monitoring Klotho levels may aid in risk stratification and management of pediatric cardiac surgery patients.
Objective:
The Klotho protein family plays important roles in several metabolic pathways. Soluble Klotho has been recently put forward as an antiaging protein, demonstrating renal and cardiovascular protective traits. Cardiopulmonary bypass (CPB) support during cardiac surgery has been implicated in several adverse outcomes in pediatric and adult patients. Our goal was to assess whether serum Klotho levels can be used to predict outcomes in children undergoing cardiac surgery with CPB due to congenital heart defects (CHDs).
Methods:
This prospective study was conducted on pediatric patients admitted to two Pediatric Cardiac Intensive Care Units, between 2012 and 2018. All patients were born with CHD and underwent corrective surgery with CPB. Sequential blood samples were analyzed by enzyme-linked immunosorbent assay for soluble Klotho levels at baseline, 2, 6, and 24 h after surgery. The association between Klotho levels and several demographic, intraoperative, and postoperative clinical and laboratory parameters was studied.
Results:
Twenty-nine children undergoing cardiac surgery with CPB support were included. Serum Klotho levels were shown to significantly decrease 2 h after surgery and increase to baseline levels after 6 h (p < .001 and p < .05, respectively). Patients with low Klotho levels 2 h after surgery were at a 32-fold higher risk for developing postoperative complications (p = .015, odds ratio < 0.03). Moreover, Klotho levels at each of the four time points were lower in patients who developed postoperative complications.
Conclusions:
Cardiac surgery with CPB results in a significant decrease of serum Klotho levels 2 h after surgery in pediatric patients with CHDs, which can be used to predict development of postoperative complications in this patient population.

