Frailty And Sarcopenia In Chronic Kidney Disease: Age-dependent Associations With Cardiovascular Risk

PURPOSE: Frailty and sarcopenia are common in chronic kidney disease (CKD) and are linked to poor cardiovascular outcomes. While frailty and sarcopenia often coexist, their unique and combined physiological impacts in CKD, across different age groups are unclear. This study aimed to identify clinical factors associated with frailty and sarcopenia in patients with CKD. METHODS: 102 patients with CKD stages III-IV (62 ± 9 yr, 71% males) underwent assessments including physical function [Short Physical Performance Battery and handgrip strength], body composition and hydration [extracellular water to total body water (ECW/TBW)] by bioimpedance, cardiovascular metrics [pulse pressure, ventricular ejection duration %, and subendocardial viability ratio (SEVR)] via arterial tonometry, and plasma inflammatory markers. Patients were divided by frailty status (met criteria for pre-frailty using handgrip strength and gait speed) and sarcopenia (met criteria for EWGSOP II probable or confirmed sarcopenia). Groups were further stratified into middle-aged [<65 (55 ± 8) yr; n = 48] and older [≥65 (69 ± 3) yr; n = 54] for subgroup analysis. RESULTS: Frail group (47.6%) had worse eGFR (39 ± 12 vs. 47 ± 12 mL/min; p = 0.004) and elevated ECW/TBW (39 ± 1 vs. 38 ± 1 %; p < 0.001), aortic pulse pressure (49 ± 9 vs. 43 ± 12 mmHg; p = 0.035) and interleukin-6 (1.6 ± 0.7 vs. 1.1 ± 0.5 pg/ml; p = 0.018), compared to the non-frail group. Sarcopenic group (19.6%) had worse eGFR, elevated ejection duration and dampened SEVR, compared to the non-sarcopenic (p < 0.05 for all). Among frail patients, those with sarcopenia (44%) had lower handgrip strength (20 ± 6 vs. 29 ± 8 kg; p = 0.004) and longer time for five-chair stands (16 ± 4 vs.10 ± 5 sec; p = 0.002) than those with frailty alone. eGFR and pulse pressure significantly predicted frailty in middle-aged, while interleukin-6 predicted frailty in the older subgroup. CONCLUSIONS: Frailty in CKD is associated with volume overload, vascular stiffness, and inflammation in an age-dependent manner, while sarcopenia is linked to increased cardiac workload and reduced myocardial perfusion, and the combined presence with worse physical function. These findings support targeted, age-specific strategies addressing cardiovascular health to mitigate functional decline and improve clinical outcomes in CKD. Supported by: NIH R01HL135183; NIH R61AT10457; NIH KL2TR002381; VA Merit I01CX001065