Structural and Functional Changes in Human Kidneys with Healthy Aging

Abstract

Aging is associated with significant changes in structure and function of the kidney, even in the absence of age-related comorbidities. On the macrostructural level, kidney cortical volume decreases, surface roughness increases, and the number and size of simple renal cysts increase with age. On the microstructural 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 in measured 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, age-related 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.

Keywords: aging; glomerular filtration rate; glomerulosclerosis; kidney volume; nephron number; nephrosclerosis.

Graphical abstract

Figure 1.

Structural and functional changes in the kidney from common co-morbidities or specific kidney diseases are additive to the underlying age-related changes that occur even in health. Healthy aging alone leads to nephrosclerosis with nephron loss and can be studied in living kidney donors. The added component of aging with expected comorbidity leads to more nephrosclerosis, larger glomeruli, and further nephron loss and can be studied in deceased kidney donors, certain autopsy settings, and patients who undergo a radical nephrectomy for a tumor. The added component of actual CKD becomes prevalent with aging and results in disease-specific changes that can be studied in patients undergoing clinically indicated biopsies for an overt nephropathy. The current single-threshold criteria-based CKD definition fails to distinguish between these three types of structural and functional changes with aging.

Figure 2.

There are degenerative macro-structural changes that occur in the human kidney with even healthy aging. There is cortical volume loss, some increase in medullary volume (not shown), increase in surface roughness, increased sinus fat, and an increase in renal cysts. These findings can be attributed to underlying nephrosclerosis with nephron loss, hypertrophy of remaining tubules, and tubular diverticuli.