Original Data

Increased Levels of Total P-Cresylsulphate and Indoxyl Sulphate are Associated with Coronary Artery Disease in Patients with Diabetic Nephropathy

Cheng-An Chiu¹, Li-Fen Lu², Teng-Hung Yu¹, Wei-Chin Hung¹, Fu-Mei Chung¹, I-Ting Tsai³, Chih-Ying Yang³, Chia-Chang Hsu⁴, Yung-Chuan Lu⁵, Chao-Ping Wang^6,7, Yau-Jiunn Lee⁸

Manuscript submitted January 3, 2011; resubmitted January 21, 2011; accepted January 27, 2011.

Keywords: total p-cresylsulphate, indoxyl sulphate, coronary artery disease, type 2 diabetes, renal function

Abstract

BACKGROUND: Indoxyl sulphate (IS) and p-cresylsulphate (PCS) are uremic toxins with similar protein-binding, dialytic clearance, and proinflammatory features. Few studies have evaluated the possible associations between these solutes and coronary artery disease (CAD) in type 2 diabetes (T2D) patients. METHODS: A hospital-based case control study was performed. A total of 209 T2D patients were divided into two groups based on the presence/absence of significant CAD (≥50% luminal reduction). Serum total PCS and IS levels were measured using the Ultra Performance LC System. The relationship between total PCS and IS levels were investigated. Coronary calcium scores and the modified Gensini score were analyzed. RESULTS: Serum total PCS and IS levels were significantly higher in patients with both T2D and significant CAD, than in non-diabetic control subjects and T2D patients without CAD (all p < 0.05). Logistic regression analysis revealed independent and significant associations between the two solutes and CAD status. Serum total PCS, IS, and numbers of diseased vessels were elevated in groups with estimated glomerular filtration rate (eGFR) of 60-89 ml/min/1.73 m² and below. Also, serum total PCS and IS levels were significantly associated with eGFR, coronary calcium scores, Gensini score, adipocytokines (adiponectin, visfatin, and leptin), and total white blood cell count. CONCLUSIONS: Serum total PCS and IS levels were elevated in patients with T2D and CAD. These increases were associated with renal function deterioration, inflammation, and coronary atherosclerosis.

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