Aging of the Urinary Tract

Overview

Declines in renal function represent one of the best documented and most dramatic physiologic alterations in human aging. In spite of great progress, important issues remain. For example, it has been difficult to explain why renal aging can be so variable between seemingly “normal” individuals and to establish which of these changes may potentially be reversible. Nevertheless, developments and continuing research in this area offer unique opportunities for improving the lives of older adults.

Glomerular Filtration Rate

Age-related declines in glomerular filtration rate (GFR) are well-established, yet contrary to general belief, GFR does not inevitably decrease with age. Among Baltimore Longitudinal Study of Aging participants, mean GFR declined approximately 8.0 mL/min per 1.73 m ² per decade from the middle of the fourth decade of life. However, these decrements were not universal, with approximately one third of these subjects showing no significant decrease in GFR over time. This high degree of interindividual variability among relatively healthy older adults has raised the hope that age-related declines in GFR may not be inevitable and could ultimately be preventable, even in the absence of an overt disease process. At the same time, clinicians wishing to prescribe renally excreted medications to healthy older adults clearly require reliable tools to estimate GFR accurately.

The decrease in GFR with age is generally not accompanied by elevations in serum creatinine levels because age-related declines in muscle mass tend to parallel those observed for GFR, causing overall creatinine production also to fall with age. Thus, serum creatinine levels generally overestimate GFR with age, and in women and underweight individuals, the serum creatinine level is most insensitive to impaired kidney function. Although many formulas have been devised for estimating creatinine clearance based on normative data, their reliability in predicting individual renal function is poor. In frail and severely ill patients on multiple medications, where the need for accurate estimation is greatest, the reliability of such estimates may be the most questionable. In consequence, timed short-duration urine collections for creatinine clearance measurement are generally recommended. In contrast to the poor predictive ability of low creatinine levels, elevations in serum creatinine levels above 132 mmol/L (1.5 mg/dL) reflect declines in GFR greater than what would be typically expected with normal aging, representing likely underlying pathology. Ultimately, even creatinine clearance has limitations and may underestimate GFR. Cystatin C, a measure of kidney function that is independent of muscle mass, has been advocated as an improved marker of reduced GFR in older adults with creatinine levels within the normal range. Although U.S. Food and Drug Administration (FDA)–approved kits for its measurement have been available since 2001, and in spite of its potential attraction in the management of frail older adults, the precise role of cystatin C measurements in clinical decision making remains to be clearly defined.

Renal Blood Flow

On average, aging is associated with a progressive decrease in renal plasma flow. Losses of 10% per decade have been described, with typical values declining from 600 mL/min in a young adult to 300 mL/min at 80 years of age. Perfusion of the renal medulla is maintained in the presence of lower blood flow to the cortex, which can be observed as patchy cortical defects on renal scans obtained in healthy older adults. Regional renal flow and GRF are determined by a balance between the vascular tone involving the afferent and efferent renal blood supply. Generally, renal vasoconstriction increases in old age, whereas the capacity of the vascular bed to dilate is decreased. Responsiveness to vasodilators (e.g., nitric oxide, prostacyclin) appears to be attenuated, whereas responsiveness to vasoconstrictors (e.g., angiotensin II) is enhanced. Basal renin and angiotensin II levels are significantly lower in older adults, and the ability of various different stimuli to activate the renin-angiotensin-aldosterone system (RAAS) is blunted.