P-cresyl sulfate accelerates left ventricular diastolic dysfunction associated with chronic kidney disease

Chronic kidney disease (CKD) favors the development of cardiovascular disease (CVD). Protein-bound uremic toxins retained in CKD patients are considered to be emerging risk factors for CVD. One uremic toxin, p-cresyl sulfate (PCS), has now been the subject of research interest with regard to its negative impact on cardiovascular system. However, the effect of PCS on CVD remains to be elucidated. In the present study, the association of PCS and left ventricular (LV) diastolic dysfunction in the clinical setting was investigated. 170 patients underwent hemodialysis (HD) treatment was evaluated with echocardiography. Serum biochemistries and PCS levels were also measured. To confirm the clinical findings, wild type C57/BL male mice were treated with PCS to study the possible acceleration of cardiac dysfunction. 8-wk-old mice underwent uninephrectomy (UNX) were randomly divided into PCS-treated (intake of 0.5 mg/ml PCS dissolved in double distilled water for 20 weeks) and control groups. At the end of the experiment, echocardiography and haemodynamic measurements were performed in each mouse. Of the 170 patients, a significantly greater prevalence of LV diastolic dysfunction was present in patients with higher serum PCS levels (>0.85 μg/ml) than those with lower serum PCS levels (≤0.85 μg/ml). Animal study showed a significantly greater prevalence of LV diastolic dysfunction in PCS-treated mice than control group. These findings suggest that PCS contributes to diastolic dysfunction and that targeting PCSmay be a therapeutic strategy in CKD.