Association Between Indoxyl Sulfate and Dialysis Initiation and Cardiac Outcomes in Chronic Kidney Disease Patients

Kullaya Takkavatakarn,1 Jeerath Phannajit,1 Suwasin Udomkarnjananun,1 Suri Tangchitthavorngul,1 Pajaree Chariyavilaskul,2,3 Patita Sitticharoenchai,4 Kearkiat Praditpornsilpa,1 Somchai Eiam-Ong,1 Paweena Susantitaphong1,5 1Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand; 2Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 3Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; 4Division of Cardiology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand; 5Research Unit for Metabolic Bone Disease in CKD Patients, Faculty of Medicine, Chulalongkorn University, Bangkok, ThailandCorrespondence: Paweena Susantitaphong, Division of Nephrology, Department of Medicine, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, 1873 RAMA IV, Bangkok, 10330, Thailand, Tel +662 256-4251, Fax +662 256-4560, Email paweena.s@chula.ac.thIntroduction: Indoxyl sulfate, a protein-bound uremic toxin, has been reported as an atherosclerosis and fibrosis accelerator. This study aimed to determine whether serum indoxyl sulfate is associated with cardiac abnormalities, cardiovascular events, and renal progression to dialysis in patients with chronic kidney disease (CKD).Methods: The prospective study enrolled 89 patients with CKD stage 3 to 5 patients. Serum biochemistry data and indoxyl sulfate were measured. All patients underwent echocardiographic examination. Global longitudinal strain (GLS) was calculated using two-dimensional speckle tracking. The clinical outcomes including cardiovascular event and dialysis initiation were recorded during a 2-year follow-up.Results: Patients were divided into 2 groups based on the median value of serum indoxyl sulfate (low and high indoxyl sulfate groups). Kaplan–Meier analysis revealed that patients with higher indoxyl sulfate (≥ 6.124 mg/L) were significantly associated with renal progression to dialysis (p < 0.001). There was no significant difference in cardiovascular events between 2 groups (p = 0.082). In addition, serum indoxyl sulfate level was independently associated with GLS (r = 0.62; p = 0.01). The risk of cardiovascular events was significantly higher in patients with impaired GLS (>− 16%) (p = 0.015).Conclusion: Serum indoxyl sulfate level was a significant predictor for CKD progression to dialysis and was correlated with GLS, a speckle tracking echocardiography parameter representing early LV systolic dysfunction. Furthermore, GLS was associated with cardiovascular events in CKD patients. Serum indoxyl sulfate measurement may help to identify the high dialysis and cardiovascular risk CKD patients beyond traditional risk factors.Graphical Abstract: Keywords: indoxyl sulfate, chronic kidney disease, echocardiographic parameters, renal outcomes, cardiovascular events