Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients.
OBJECTIVE
As a major component of uremic syndrome, cardiovascular disease is largely responsible for the high mortality observed in chronic kidney disease (CKD). Preclinical studies have evidenced an association between serum levels of indoxyl sulfate (IS, a protein-bound uremic toxin) and vascular alterations. The aim of this study is to investigate the association between serum IS, vascular calcification, vascular stiffness, and mortality in a cohort of CKD patients.


METHODS
One-hundred and thirty-nine patients (mean +/- SD age: 67 +/- 12; 60% male) at different stages of CKD (8% at stage 2, 26.5% at stage 3, 26.5% at stage 4, 7% at stage 5, and 32% at stage 5D) were enrolled.


RESULTS
Baseline IS levels presented an inverse relationship with renal function and a direct relationship with aortic calcification and pulse wave velocity. During the follow-up period (605 +/- 217 d), 25 patients died, mostly because of cardiovascular events (n = 18). In crude survival analyses, the highest IS tertile was a powerful predictor of overall and cardiovascular mortality (P = 0.001 and 0.012, respectively). The predictive power of IS for death was maintained after adjustment for age, gender, diabetes, albumin, hemoglobin, phosphate, and aortic calcification.


CONCLUSIONS
The study presented here indicates that IS may have a significant role in the vascular disease and higher mortality observed in CKD patients.
Barreto
Fellype C
FC
INSERM ERI-12, Divisions of Clinical Pharmacology and Nephrology, Amiens University Hospital, Avenue Rene Laennec, F-80054 Amiens, France.
Barreto
Daniela V
DV
Liabeuf
Sophie
S
Meert
Natalie
N
Glorieux
Griet
G
Temmar
Mohammed
M
Choukroun
Gabriel
G
Vanholder
Raymond
R
Massy
Ziad A
ZA
D000328:Adult; D000368:Aged; D002908:Chronic Disease; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007200:Indican / Q000097:blood*; D007674:Kidney Diseases / Q000097:blood / Q000150:complications / Q000401:mortality*; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D016016:Proportional Hazards Models; D014652:Vascular Diseases / Q000209:etiology*
D010281:Parathyroid Hormone; D007200:Indican
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