Structural and Functional Changes With the Aging Kidney

Abstract

Senescence or normal physiologic aging portrays the expected age-related changes in the kidney as compared to a disease that occurs in some but not all individuals. The microanatomical structural changes of the kidney with older age include a decreased number of functional glomeruli from an increased prevalence of nephrosclerosis (arteriosclerosis, glomerulosclerosis, and tubular atrophy with interstitial fibrosis), and to some extent, compensatory hypertrophy of remaining nephrons. Among the macroanatomical structural changes, older age associates with smaller cortical volume, larger medullary volume until middle age, and larger and more numerous kidney cysts. Among carefully screened healthy kidney donors, glomerular filtration rate (GFR) declines at a rate of 6.3 mL/min/1.73 m(2) per decade. There is reason to be concerned that the elderly are being misdiagnosed with CKD. Besides this expected kidney function decline, the lowest risk of mortality is at a GFR of ≥75 mL/min/1.73 m(2) for age <55 years but at a lower GFR of 45 to 104 mL/min/1.73 m(2) for age ≥65 years. Changes with normal aging are still of clinical significance. The elderly have less kidney functional reserve when they do actually develop CKD, and they are at higher risk for acute kidney injury.

Keywords: Aging; Glomerular filtration rate; Glomerulosclerosis; Kidney function; Nephrosclerosis.

Fig 1. Sclerosis score by age group among 1203 living kidney donors

Sclerosis score is defined as the total number of chronic histological abnormalities between any global glomerulosclerosis, any tubular atrophy, interstitial fibrosis >5% and any arteriosclerosis. In the figure, a score of 0 (absence of any abnormality) is white, a score of 4 (presence of all four pathological abnormalities) is black, and intermediate scores are on a gray scale.

Fig 2. Effect of age on total kidney, cortical and medullar volumes

(A) Among 1281 living kidney donors cortical volume declines, whereas medullary volume increases, making total kidney volume relatively stable until about 50 years of age. After which, medullary volume does not increase anymore and total kidney volume begins to decline. Results were normalized to the total kidney, cortical or medullar volumes in 18-19-year age group. (B) Schematic illustration of cortical and medullary volume changes with aging (Modified with permission from Kidney International).

Fig 3. Number of cortical and medullary simple cysts ≥5mm by age among 1948 potential living kidney donors

In the figure fraction with no cysts is shown in white, whereas black represents the fraction of 3 or more cysts. Intermediate fractions on a gray scale represent presence of 1 or 2 cysts.

Fig 4

GFR declines with normal aging whether measured or estimated (MDRD study equation) among 1057 potential kidney donors in both women (A) and men (B).

Fig 5. Adjusted Hazard Ratios for all-cause mortality by categories of eGFR and age in patients with little or no albuminuria

Associations of eGFR with all-cause mortality are presented across 4 different age groups (18-54, 55-64, 65-74 and >75 years) for <10 and 10-29 mg/g urine albumin to creatinine ratios. Reference group for individuals 18-54 years old is eGFR >105 ml/min/1.73m², for 55-64-year-old is eGFR 90-104 ml/min/1.73m², for 65-74-year-old is 75-90 ml/min/1.73m², and for older than 75 years, 60-74 ml/min/1.73m². Adjusted hazard ratios were based on pooled estimates from 33 population cohort studies. Note the shift of low risk eGFR groups to lower ranges of eGFR with older age (dashed arrow). Figure calculated from published tables.