Relation of Plasma Indoxyl Sulfate Levels and Estimated Glomerular Filtration Rate to Left Ventricular Diastolic Dysfunction

Abstract

The prognosis of patients with diastolic heart failure (HF) is as poor as that of patients with systolic HF. Greater chronic kidney disease-associated mortality occurs in patients with left ventricular (LV) diastolic HF than in those with systolic HF. Indoxyl sulfate (IS), a uremic toxin, directly affects cardiac cells adversely in in vitro experiments. We investigated the association of IS, a uremic toxin, and chronic kidney disease with LV diastolic dysfunction in the clinical setting. The present study included 204 consecutive patients with preserved LV systolic function. To evaluate LV function, all patients underwent echocardiography. To measure the plasma IS levels and estimated glomerular filtration rate (eGFR), blood samples were obtained. Of the 204 patients, 75 (37%) had LV diastolic dysfunction. A significantly lower prevalence of LV diastolic dysfunction was present in patients with lower plasma IS levels (≤1.0 μg/ml) than those with greater plasma IS levels (38 [29%] vs 37 [51%], p <0.001). Furthermore, a significantly lower prevalence of LV diastolic dysfunction was present in patients with lower plasma IS levels and preserved eGFR than those with greater plasma IS levels and preserved eGFR, those with lower plasma IS levels and a reduced eGFR, or those with greater plasma IS levels and reduced eGFR (20 [21%] vs 18 [53%], p = 0.001; 20 [21%] vs 18 [46%], p = 0.004; and 20 [21%] vs 19 [56%], p <0.001, respectively). In conclusion, greater plasma IS levels or a reduced eGFR, or both, represent an increased risk of LV diastolic dysfunction.