Structural and functional changes in human kidneys with healthy aging

Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities.On themacrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increasewith age.Onthemicrostructural level, the histologic signs of nephrosclerosis (arteriosclerosis/arteriolosclerosis, global glomerulosclerosis, interstitial fibrosis, and tubular atrophy) all increase with age. The decline of nephron number is accompanied by a comparable reduction inmeasured whole-kidney GFR. However, single-nephron GFR remains relatively constant with healthy aging as does glomerular volume. Only when glomerulosclerosis and arteriosclerosis exceed that expected for age is there an increase in single-nephron GFR. In the absence of albuminuria, agerelated reduction in GFR with the corresponding increase in CKD (defined by an eGFR<60 ml/min per 1.73 m²) has been shown to associate with a very modest to no increase in age-standardized mortality risk or ESRD. These findings raise the question of whether disease labeling of an age-related decline in GFR is appropriate. These findings also emphasize the need for a different management approach for many elderly individuals considered to have CKD by current criteria.