Wu C.-H.YA-WEN YANGHung S.-C.Kuo K.-L.KWAN-DUN WUVIN-CENT WUHsieh T.-C.for the National Taiwan University Study Group on Acute Renal Failure (NSARF)2021-11-302021-11-3020171932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-85019140851&doi=10.1371%2fjournal.pone.0176847&partnerID=40&md5=430c2bfed8aaf0da961f45dd6b76c26dhttps://scholars.lib.ntu.edu.tw/handle/123456789/588429Background: The benefit of alpha-Ketoanalogues (KA) supplementation for chronic kidney disease (CKD) patients that followed low-protein diet (LPD) remains undetermined. Methods: We extracted longitudinal data for all CKD patients in the Taiwan National Health Insurance from January 1, 2000 through December 31, 2010. A total of 1483 patients with anemic advanced CKD treated with LPD, who started KA supplementation, were enrolled in this study. We analyzed the risks of end stage renal disease and all-cause mortality using Cox proportional hazard models with influential drugs as time-dependent variables. Results: A total of 1113 events of initiating long-term dialysis and 1228 events of the composite outcome of long-term dialysis or death occurred in patients with advanced CKD after a mean follow-up of 1.57 years. Data analysis suggests KA supplementation is associated with a lower risk for long-term dialysis and the composite outcome when daily dosage is more than 5.5 tablets. The beneficial effect was consistent in subgroup analysis, independent of age, sex, and comorbidities. Conclusions: Among advanced CKD patients that followed LPD, KA supplementation at an appropriate dosage may substantially reduce the risk of initiating long-term dialysis or of developing the composite outcome. KA supplementation represents an additional therapeutic strategy to slow the progression of CKD. ? 2017 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.[SDGs]SDG3ketosteril; adult; anemia; Article; cause of death; chronic kidney failure; cohort analysis; dose response; end stage renal disease; female; hemodialysis; human; longitudinal study; major clinical study; male; mortality risk; renal protection; risk reduction; supplementation; aged; complication; epidemiology; Kidney Failure, Chronic; middle aged; mortality; proportional hazards model; Taiwan; Aged; Anemia; Cohort Studies; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Proportional Hazards Models; Renal Dialysis; Taiwanjournal article10.1371/journal.pone.0176847284755912-s2.0-85019140851