The Role of Brain Structure in Explaining Physical Functioning in Male Veterans With Impaired Kidney Function

Abstract

Background Older adults with chronic kidney disease (CKD) experience deficits in physical function and cardiorespiratory fitness at higher rates than older adults without impaired renal function. Emerging evidence suggests covert brain pathology may be contributing to these functional impairments. However, much of the previous work has not controlled for common cardiac comorbidities also associated with brain pathology and reduced physical function. The present analysis investigates differences in global brain structure, physical performance, and cardiorespiratory fitness between older adults with CKD and hypertensive controls without kidney disease. This analysis also explores the role of brain structure in mediating the relationship between renal function and physical function while controlling for common cardiac comorbidities. Methods Forty-one older male veterans with CKD and 30 hypertensive controls were recruited from clinics at the VA Maryland Health Care System to complete physical function assessments (Six Minute Walk Test (6MWT), Short Physical Performance Battery, Timed Up and Go), a graded exercise treadmill test to evaluate fitness, and brain magnetic resonance imaging to quantify total gray matter volume, total white matter volume, and total white matter lesion volume. Group differences were assessed, then mediation of brain structure on the relationships between continuous measures of renal and physical function was evaluated with all participants combined. Results Older male veterans with CKD had lower gray matter volume (597.5 ± 46.9 vs. 624.4 ± 51.4 cc), poorer endurance (6MWT: 431.2 ± 112.9 vs. 484.1 ± 99.4 m), and lower cardiorespiratory fitness (VO₂ peak: 19.4 ± 5.2 vs. 25.1 ± 7.5 mL/kg/min) compared with hypertensive controls. Global gray matter volume, but not total white matter volume nor white matter lesion volume, mediated the relationships between renal and physical function measures. Mediation held after accounting for common cardiac comorbidities and risk factors. Conclusions CKD-specific pathways, distinct from traditional hemodynamic or ischemic mechanisms, may be contributing to the impaired physical functioning observed among those with impaired renal function.