title: 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.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan.
authors.forename: Cheng-Jui
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Vincent
authors.initials: V
authors.lastname: Wu
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Pei-Chen
authors.initials: PC
authors.lastname: Wu
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan; Graduate Institute of Medical Science, Taipei Medical University, Taipei, Taiwan; Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
authors.forename: Chih-Jen
authors.initials: CJ
authors.lastname: Wu
mesh_terms: D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology*; D003408:Cresols / Q000097:blood*; D006801:Humans; D007200:Indican / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications* / Q000401:mortality; D012307:Risk Factors; D013463:Sulfuric Acid Esters / Q000097:blood*; D014118:Toxins, Biological / Q000097:blood; D014511:Uremia / Q000097:blood
chemical_list: D015415:Biomarkers; D003408:Cresols; D013463:Sulfuric Acid Esters; D014118:Toxins, Biological; C408690:4-cresol sulfate; D007200:Indican