Meta-Analysis of the Associations of p-Cresyl Sulfate (PCS) and Indoxyl Sulfate (IS) with Cardiovascular Events and All-Cause Mortality in Patients with Chronic Renal Failure

• Published in: PloS one Vol. 10; no. 7; p. e0132589
• Main Authors: Lin, Cheng-Jui, Wu, Vincent, Wu, Pei-Chen, Wu, Chih-Jen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14-07-2015; Public Library of Science (PLoS)
• Subjects: Biomarkers - blood; Cardiovascular diseases; Cardiovascular Diseases - etiology; Cresols - blood; Dialysis; End-stage renal disease; English language; Failure; Health risk assessment; Health risks; Humans; Indican - blood; Kidney diseases; Kidney Failure, Chronic - blood; Kidney Failure, Chronic - complications; Kidney Failure, Chronic - mortality; Medical ethics; Meta-analysis; Mortality; Patients; Peritoneal dialysis; Renal failure; Risk; Risk Factors; Serum levels; Sulfates; Sulfuric Acid Esters - blood; Systematic review; Toxins; Toxins, Biological - blood; Uremia - blood
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0132589

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are protein-bound uremic toxins that increase in the sera of patients with chronic kidney disease (CKD), and are not effectively removed by dialysis. The purpose of this meta-analysis was to investigate the relationships of PCS and IS with cardiovascular events and all-cause mortality in patients with CKD stage 3 and above.
Medline, Cochrane, and EMBASE databases were searched until January 1, 2014 with combinations of the following keywords: chronic renal failure, end-stage kidney disease, uremic toxin, uremic retention, indoxyl sulfate, p-cresyl sulfate. Inclusion criteria were: 1) Patients with stage 1 to 5 CKD; 2) Prospective study; 3) Randomized controlled trial; 4) English language publication. The associations between serum levels of PCS and IS and the risks of all-cause mortality and cardiovascular events were the primary outcome measures. Of 155 articles initially identified, 10 prospective and one cross-sectional study with a total 1,572 patients were included. Free PCS was significantly associated with all-cause mortality among patients with chronic renal failure (pooled OR = 1.16, 95% CI = 1.03 to 1.30, P = 0.013). An elevated free IS level was also significantly associated with increased risk of all-cause mortality (pooled OR = 1.10, 95% CI = 1.03 to 1.17, P = 0.003). An elevated free PCS level was significantly associated with an increased risk of cardiovascular events among patients with chronic renal failure (pooled OR = 1.28, 95% CI = 1.10 to 1.50, P = 0.002), while free IS was not significantly associated with risk of cardiovascular events (pooled OR = 1.05, 95% CI = 0.98 to 1.13, P = 0.196).
Elevated levels of PCS and IS are associated with increased mortality in patients with CKD, while PCS, but not IS, is associated with an increased risk of cardiovascular events.