title: Oxidative Stress as Estimated by Gamma-Glutamyl Transferase Levels Amplifies the Alkaline Phosphatase-Dependent Risk for Mortality in ESKD Patients on Dialysis.
abstract: Alkaline phosphatase (Alk-Phos) is a powerful predictor of death in patients with end-stage kidney disease (ESKD) and oxidative stress is a strong inducer of Alk-Phos in various tissues. We tested the hypothesis that oxidative stress, as estimated by a robust marker of systemic oxidative stress like γ-Glutamyl-Transpeptidase (GGT) levels, may interact with Alk-Phos in the high risk of death in a cohort of 993 ESKD patients maintained on chronic dialysis. In fully adjusted analyses the HR for mortality associated with Alk-Phos (50 IU/L increase) was progressively higher across GGT quintiles, being minimal in patients in the first quintile (HR: 0.89, 95% CI: 0.77-1.03) and highest in the GGT fifth quintile (HR: 1.13, 95% CI: 1.03-1.2) (P for the effect modification = 0.02). These findings were fully confirmed in sensitivity analyses excluding patients with preexisting liver disease, excessive alcohol intake, or altered liver disease biomarkers. GGT amplifies the risk of death associated with high Alk-Phos levels in ESKD patients. This observation is compatible with the hypothesis that oxidative stress is a strong modifier of the adverse biological effects of high Alk-Phos in this population.
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, 89124 Reggio Calabria, Italy; Department of Internal Medicine, Erasmus University Medical Centre, 3015 CE Rotterdam, Netherlands.
authors.forename: Claudia
authors.identifier: 0000-0002-4967-0916
authors.initials: C
authors.lastname: Torino
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Centre, 3015 CE Rotterdam, Netherlands.
authors.forename: Francesco
authors.initials: F
authors.lastname: Mattace-Raso
authors.affiliation: Department of Internal Medicine, Erasmus University Medical Centre, 3015 CE Rotterdam, Netherlands.
authors.forename: Jan L C M
authors.initials: JL
authors.lastname: van Saase
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, 89124 Reggio Calabria, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Postorino
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, 89124 Reggio Calabria, Italy.
authors.forename: Giovanni Luigi
authors.initials: GL
authors.lastname: Tripepi
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, 89124 Reggio Calabria, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mallamaci
authors.affiliation: CNR-IFC and Nephrology, Dialysis and Transplantation Unit, Ospedali Riuniti, c/o EUROLINE S.r.l., Via Vallone Petrara 57-59, 89124 Reggio Calabria, Italy.
authors.forename: Carmine
authors.identifier: 0000-0002-6616-1996
authors.initials: C
authors.lastname: Zoccali
authors.affiliation: CNR-IFC, Clinical Epidemiology and Physiopathology of Renal Diseases and Hypertension of Reggio Calabria, 89124 Reggio Calabria, Italy.
authors.lastname: Progredire Study Group
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004796:Clinical Enzyme Tests; D005260:Female; D006801:Humans; D007558:Italy; D007676:Kidney Failure, Chronic / Q000097:blood / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012042:Registries; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality*; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D015415:Biomarkers; D005723:gamma-Glutamyltransferase; C554782:gamma-glutamyltransferase, human; D000469:Alkaline Phosphatase