Yael Einbinder1,2, Alla Shnaider3, Khaled Ghanayem2, Anna Basok3, Boris Rogachev3, Yotam Lior4,5, Yosef Shmuel Haviv3, Keren Cohen-Hagai1,2, Naomi Nacasch1, Ilan Rozenberg1, Sydney Benchetrit1,2, Tali Zitman-Gal1,2, Amos Douvdevani6,7. 1. Department of Nephrology and Hypertension, Meir Medical Center, Kfar Saba, Israel. 2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Department of Nephrology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel. 4. Department of Clinical Biochemistry and Pharmacology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel. 5. Clinical Research Center, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel. 6. Department of Nephrology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel, amosd@bgu.ac.il. 7. Department of Clinical Biochemistry and Pharmacology, Soroka University Medical Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel, amosd@bgu.ac.il.
Abstract
BACKGROUND: Predicting the mortality risk of patients un-dergoing hemodialysis (HD) is challenging. Cell-free DNA (cfDNA) is released into circulation from dying cells, and its elevation is predictive of unfavorable outcome. In a pilot study, we found post-HD cfDNA level to be a predictor of all-cause mortality. Thus, the aim of this study was to confirm the prognostic power of cfDNA in a larger prospective cohort study conducted at 2 medical centers. METHODS: CfDNA levels were measured by a rapid fluorometric assay on sera obtained before and after 1 HD session. One hundred fifty-three patients were followed up to 46 months for mortality during which time 47 patients died. We compared the predictive value of cfDNA to age, comorbidities, and standard blood tests. RESULTS: Examining standard blood tests, only post-HD cfDNA levels were elevated in the non-survivor group compared to survivors (959 vs. 803 ng/mL, p = 0.04). Pre- and post-HD cfDNA levels correlated with age and diabetes. Patients with elevated cfDNA (>850 ng/mL) showed lower survival than those with normal levels. A Cox proportional hazard regression model demonstrated a significant hazard ratio of 1.92 for post-HD cfDNA levels. Logistic regression models showed that post-HD cfDNA was a significant predictor of mortality at 1-3 years with odd ratios of 4.61, 4.36, and 6.22, respectively. CONCLUSIONS: Post-HD cfDNA level was superior to standard blood tests and could serve as a biomarker to assist in decision-making for HD-treated patients.
BACKGROUND: Predicting the mortality risk of patients un-dergoing hemodialysis (HD) is challenging. Cell-free DNA (cfDNA) is released into circulation from dying cells, and its elevation is predictive of unfavorable outcome. In a pilot study, we found post-HD cfDNA level to be a predictor of all-cause mortality. Thus, the aim of this study was to confirm the prognostic power of cfDNA in a larger prospective cohort study conducted at 2 medical centers. METHODS: CfDNA levels were measured by a rapid fluorometric assay on sera obtained before and after 1 HD session. One hundred fifty-three patients were followed up to 46 months for mortality during which time 47 patientsdied. We compared the predictive value of cfDNA to age, comorbidities, and standard blood tests. RESULTS: Examining standard blood tests, only post-HD cfDNA levels were elevated in the non-survivor group compared to survivors (959 vs. 803 ng/mL, p = 0.04). Pre- and post-HD cfDNA levels correlated with age and diabetes. Patients with elevated cfDNA (>850 ng/mL) showed lower survival than those with normal levels. A Cox proportional hazard regression model demonstrated a significant hazard ratio of 1.92 for post-HD cfDNA levels. Logistic regression models showed that post-HD cfDNA was a significant predictor of mortality at 1-3 years with odd ratios of 4.61, 4.36, and 6.22, respectively. CONCLUSIONS: Post-HD cfDNA level was superior to standard blood tests and could serve as a biomarker to assist in decision-making for HD-treated patients.