Teresa Arcidiacono1, Lorenza Macrina1,2, Simone Premaschi3, Arianna Bologna1,2, Giulia Magni1,2, Nadia Foligno1,2, Monica Avino1,2, Cristina Belloni3, Nicola Palmieri4, Ferruccio Conte4, Sergio Bisegna4, Marco Simonini1, Giorgio Slaviero1, Massimo Locatelli3, Giuseppe Vezzoli5,6. 1. Nephrology and Dialysis Unit, Genomics of Renal Diseases and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. 2. Postgraduate School of Nephrology, Vita Salute San Raffaele University, 20132, Milan, Italy. 3. Laboratory Medicine Service, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy. 4. Nephrology and Dialysis Unit, Uboldo Hospital, Cernusco sul Naviglio, Milan, Italy. 5. Nephrology and Dialysis Unit, Genomics of Renal Diseases and Hypertension Unit, IRCCS San Raffaele Scientific Institute, Via Olgettina, 60, 20132, Milan, Italy. vezzoli.giuseppe@hsr.it. 6. Postgraduate School of Nephrology, Vita Salute San Raffaele University, 20132, Milan, Italy. vezzoli.giuseppe@hsr.it.
Abstract
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.
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.
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