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Background: Interactions between chronic kidney disease (CKD) and several comorbidities may potentially affect prognosis of older hospitalized patients. This study aims at evaluating the prognostic interactions between estimated glomerular filtration rate (eGFR), anemia, sarcopenia, functional and cognitive dysfunction, and 3-year mortality among older patients discharged from acute care hospitals., Methods: Our series consisted of 504 older adults enrolled in a multicenter observational study carried out in twelve Acute Geriatric and Internal Medicine wards throughout Italy. CKD was defined as an eGFR< 60 ml/min/1.73 m 2 . Anemia, Short Portable Status Mental Questionnaire (SPMSQ), Basic Activities of Daily Living (BADL), sarcopenia, and Charlson index were considered in the analysis. 3-year survival was investigated by Cox regression and prognostic interactions among study variables were assessed by survival tree analysis. Accuracy of different survival models was investigated by C-index., Results: eGFR < 30 mL/min/1.73 m 2 , anemia, sarcopenia, SPMSQ ≥ 5, and impairment in 1 or more BADL were significantly associated with mortality. Survival tree analysis showed that patients with eGFR < 35.32 ml/min/1.73 m 2 and SPMSQ ≥ 5 had the highest risk of mortality [hazard ratio (HR): 5.49, 95%CI: 3.04-9.94] followed by those with eGFR < 35.32 ml/min/1.73 m 2 , hemoglobin < 11.95 g/dL and SPMSQ < 5 (HR:3.65; 95%CI: 2.21-6.02) and those with eGFR 35.32-47.99 ml/min/1.73 m 2 and sarcopenia (HR:3.65; 95%CI: 1.99-6.69). Survival tree leaf node membership had good accuracy in predicting the study outcome (C-index: 0.73, 95%CI:0.70-0.76)., Conclusions: Interactions among study risk factors designed distinct risk profiles in older patients discharged from acute care hospitals, that may help identify patients needing targeted interventions and appropriate follow-up after discharge., (Copyright © 2021. Published by Elsevier B.V.)