Serum concentrations of free indoxyl and p-cresyl sulfate are associated with mineral metabolism variables and cardiovascular risk in hemodialysis patients

Background: Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are uremic toxins associated with cardiovascular outcome in CKD patients. The present work is an analysis of the association of serum free, total IS and PCS with cardiovascular events and calcium-phosphate metabolism variables in hemodialysis patients. Methods: Serum levels of total and free IS and PCS were measured in 139 hemodialysis patients. Their relationship with calcium-phosphate metabolism variables were tested in an observational cohort study. In addition, their association with cardiovascular events was investigated during a 4-year follow-up. Results: Patients in the highest tertile (T3) of serum free IS showed lower serum 1,25(OH)₂D compared to patients in the middle (T2) and lowest tertile (T1); in addition to this, T3 patients showed lower serum irisin than T1 patients and lower serum PTH than all the other subjects (T1 + T2) combined. Serum PTH was also measured during the two years after the baseline measurement and was higher in patients in the T1 than in those in the T3 of serum free IS. Cox regression analysis showed that cardiovascular risk was lower in T1 patients than in those in the T3 of serum free PCS, both using a univariate (OR 2.55, 95% CI 1.2–5.43; p = 0.015) or multivariate model (OR 2.48, 95% CI 1.12–5.51; p = 0.003). Conclusions: Serum free IS may be associated with PTH and 1,25(OH)₂D secretion, whereas free PCS may predict cardiovascular risk in hemodialysis patients. Graphical abstract: <fig id="Figa" position="anchor"> <graphic position="anchor" specific-use="HTML" mime-subtype="PNG" href="MediaObjects/40620_2022_1271_Figa_HTML.png" id="MO1"></graphic> </fig>