What are the characteristics of normal aging in the kidney, including kidney size, Renin-Angiotensin-Aldosterone System (RAAS) activity, and urinary creatinine clearance after age 70?

From the Guidelines

Decreased urinary creatinine clearance over age 70 is the normal aging change in the kidney, with a decline in kidney function of about 1% per year after age 40, and more noticeable decreases after age 70, due to reduced renal blood flow, decreased glomerular filtration rate, and loss of nephrons, as noted in studies such as 1. The characteristics of normal aging in the kidney include:

• Decreased kidney size, not enlarged kidneys, which would indicate pathology such as obstruction, inflammation, or cysts
• Decreased Renin-Angiotensin-Aldosterone System (RAAS) activity, which tends to decrease with age, not increase
• Decreased urinary creatinine clearance, which reflects the natural reduction in kidney function and explains why medication dosages often need adjustment in elderly patients, particularly for drugs eliminated by the kidneys, as discussed in 1 After age 40, kidney function typically declines, with more noticeable decreases after age 70, and this decline occurs due to reduced renal blood flow, decreased glomerular filtration rate, and loss of nephrons, as noted in 1. Some key points to consider when evaluating kidney function in older adults include:
• The use of equations such as the CKD-EPI equation to estimate glomerular filtration rate (eGFR) and adjust dose requirements of renally cleared drugs, as recommended in 1
• The potential for misclassification of kidney disease by one stage in >30% of participants using creatinine-based equations, and the potential benefits of using equations based on cystatin C alone or in combination with creatinine, as discussed in 1
• The importance of accurate determination of eGFR to adjust dose requirements of renally cleared drugs and minimize the risk of adverse effects, as noted in 1 Despite the decline in kidney function with age, most elderly individuals maintain adequate kidney function for normal physiological needs unless additional kidney disease is present, as noted in 1.

From the Research

Characteristics of Normal Aging in the Kidney

• Kidney size and volume decrease with age, accompanied by intrarenal vascular changes 2
• The number of glomeruli decreases and the mass of the juxtamedullary nephrons falls, resulting in a decrease in the filtration area of the glomerular basement membrane and decreased permeability 2
• The glomerular filtration rate (GFR) is reduced with aging, with a progressive linear decline in clearance from 140 ml/min/1.73m2 at age 30 to 97 at age 80 3
• Creatinine clearance falls at a rate approximating 1% per year, with an increasing variance in creatinine clearances making it increasingly important to adjust drug dosages for changes in renal function 4
• Serum creatinine concentration is an insensitive indicator of renal function in the elderly, and deduction of creatinine clearance from serum creatinine concentration, weight, and age using formulae gives only approximate values, usually too high 2

Renin-Angiotensin-Aldosterone System (RAAS) Activity

• There is no direct evidence in the provided studies regarding the changes in RAAS activity with age

Urinary Creatinine Clearance after Age 70

• Creatinine clearance is reduced with aging, with a decline in clearance from 140 ml/min/1.73m2 at age 30 to 97 at age 80 3
• The formula of Cockcroft and Gault shows the best correlation with creatinine clearance in the extremely elderly subjects, except in extremely elderly women 5
• Using estimated glomerular filtration rate (eGFR) overestimates kidney function for 3-28% of those aged ≥65 years, and for 13-58% of those aged ≥85 years, whereas creatinine clearance (Cockcroft-Gault) provides a more accurate estimate of kidney function 6