Age-Related Increase in Plasma Urea Level and Decrease in Fractional Urea Excretion

Abstract

This study confirms in humans an age-related increase in plasma urea levels (r ‫؍‬ 0.62; P < 0.001; y ‫؍‬ 0.229x ؉ 18.26) and no correlation between plasma creatinine and age (r ‫؍‬ 0.06; NS). Fractional urea excretion (FE urea) decreases with age (r ‫؍‬ ؊0.41; P < 0.001; y ‫؍‬ ؊0.226x ؉ 55). Comparing urea and creatinine clearances, measured in 19 young and in 15 old women, a larger decrease of urea clearance (؊56%) compared with the creatinine clearance (؊43%) was observed as expected, explaining the lower FE urea in the elderly. In old women, the daily urea excretion was 27% and the daily creatinine excretion was 42% lower than in young women. An age-related decrease of same magnitude in both creatinine production and creatinine clearance explains why plasma creatinine remains stable with increasing age. The observation of a more important decrease in urea clearance (56%) than in urea production (27%) in older women led to an expected increase in plasma urea of 29%. These observations incited a comparison of biochemical profiles from younger and older patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Young patients with SIADH present lower mean plasma urea (18 ؎ 8 mg/dl) and higher mean FE urea (58 ؎ 14%), compared with both young control subjects (mean plasma urea 27 ؎ 7 mg/dl; mean FE urea 46 ؎ 10%) and old patients with SIADH (mean plasma urea 29 ؎ 8 mg/dl; mean FE urea 44 ؎ 15%). Physicians must realize that frankly low plasma urea values and high FE urea values can be expected only in young patients with SIADH, whereas old patients with SIADH will present values of plasma urea and FE urea in the same range than young control subjects. However, old patients with SIADH show still lower mean plasma urea values and higher mean FE urea values, compared with old control subjects (mean plasma urea 39 ؎ 8 mg/dl; mean FE urea 36 ؎ 9%), in whom plasma urea values between 40 and 50 mg/dl must be considered as usual.Clin J Am Soc Nephrol 1: 909 -914, 2006. doi: 10.2215/CJN.00320106 B oth plasma urea and fractional urea excretion (FE urea) are considered as useful biochemical parameters in the differential diagnosis of salt-depleted hyponatremic and patients with the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) (1-3). Hyponatremia in SIADH is usually associated with a low plasma urea as a result of a high FE urea (4), whereas in hyponatremia that is caused by salt depletion (SD), plasma urea usually is increased as a result of an abnormal low FE urea (5) (prerenal uremia). Unfortunately, the usefulness of plasma urea and FE urea in discriminating SIADH and SD is limited by an important degree of "overlapping" values. In earlier work (6), we noted that plasma urea values Ͼ30 mg/dl were observed in 82% of patients with SD, whereas plasma urea values Ͻ30 mg/dl were seen in 79% of patients with SIADH. Eighty-two percent of the patients with salt-depleted hyponatremic presented FE urea values Ͻ50%, but only 52% of the patients with SIADH showed FE urea values Ͼ50...

Nephrogenic Syndrome of Inappropriate Antidiuresis in Adults

“…This variable expressivity could be explained by the influence of modificator genes, as for many genetic diseases, on one hand, and by the major environmental influence of differences and variation in fluid and/or solute intake on the other hand (15). Idiopathic chronic SIADH is frequent in the elderly (16); it is not excluded that some of these patients in fact present NSIAD, which is "revealed" late in life because of the widely know decrease in solute intake in the elderly (17,18).…”

Clinical Laboratory Evaluation of the Syndrome of Inappropriate Secretion of Antidiuretic Hormone

“…Reprinted from reference (36), with permission. increase in plasma urea level and decrease in fractional urea excretion (Figure 4), which explains the difference in urea and FEurea between young and old patients with SIADH (mean urea and FEurea in young patients with SIADH 18 mg/dl and 58%, respectively, and in old patients 29 mg/dl and 44%, respectively) (38). As for urea, the level of serum uric acid is known to be partially dependent on its renal clearance, which is influenced by different factors, one of the most important being EV.…”

“…Hyponatremia in young patients with SIADH is usually associated with low plasma creatinine concentration, whereas this is not the case in old patients with SIADH (37,38). SIADH is also associated with low plasma urea levels as a result of a high renal clearance (39), whereas in hyponatremia that is caused by salt depletion, plasma urea usually is increased as a result of an abnormal low FEurea (40) (prerenal uremia).…”

Pathophysiology of the aging kidney and therapeutic interventions

“…8 In the elderly, the production of creatinine also decreases with age, whereas the secretion of creatinine from the tubules increases. 22 Therefore, although the glomerular filtration rate declines in aging kidneys, the serum creatinine levels may remain stable, 23 which further highlights the limitation of using relative insensitive serum creatinine levels as a marker of renal function.…”