© Borgis - New Medicine 4/2003, s. 94-96
Zygmunt Chodorowski1, Przemyslaw Rutkowski2, Boleslaw Rutkowski2, Jacek Sein Anand1
Effects of age and low sodium diet on glomerular filtration rate, plasma renal flow, urinary aldosterone excretion rate and ability of renal sodium conservation in the elderly
1 1st Department of Internal Medicine and Toxicology, The Medical University of Gdansk, Poland
Head: prof. Zygmunt Chodorowski, MD, PhD
2 Department of Nephrology, Transplantology and Internal Medicine,
The Medical University of Gdansk, Poland
Head: prof. Boleslaw Rutkowski, MD, PhD
Summary
The objective of the study was to assess the effects of age and low-sodium diet (Na + < 10 mmol/24 h) on glomerular filtration rate, effective renal plasma flow, 24 h urinary aldosterone excretion rate and renal sodium conservation ability in the elderly.
The research was carried out in two patient groups: a control group (I) of 23 healthy subjects (11 women) aged 18-39 years (mean 30 years) and a study group of 22 clinically healthy subjects (10 women) aged 66-83 (mean 73 years). None of the subjects had any abnormal changes in the kidneys, liver, cardiovasular or edocrine organs. In statistical analysis Student´s t and paired tests were used. In the elderly on normal sodium diet (Na+ ave 150 mmol/24 h) glomerular filtration rate was decreased by 39.5%, 51Cr clearance by 38.1%, 125J-hippurate clearance by 47.9% and 24-hour urinary aldosterone excrection rate by 35.8%; filtration fraction was elevated by 15.7%. The results were statisticalyy significant as compared with those of group I. A fouir-day dietary sodium intake had no effect on the renal function parameters; however, in the elderly subjects it reduced 24-hour urinary sodium excretion by 26.5%, and in the control group by 65.9%. This difference indicated an increased urinary sodium loss in the elderly group. Additionally, low sodium diet increased the urinary sodium aldosterone excretion in both groups; however, this increase was lower in the elderly subjects.
INTRODUCTION
Age-related involutional changes in the kidneys, begin to appear soon over the age of 40 years. Apart from not clearly defined factors, the main causes leading to progressive renal atrophy include atheromatous lesions in the renal arteries and atherosclerosis in the intrarenal arterioles, the latter, however, are usually due to a long-standing arterial hypertension. Occasionally, also caused by degenerative processes in the renal tubules, the arterial lumen undergoes segmental dilatation, resulting tubular diverticula, are colonised by multiple bacteria; those, in favourable conditions, become the source of urinary infection. In response to ischaemia and degeneration of some nephron structures, the interstitial tissue produces cellular, mainly polymorphonuclear infiltrates, which in time undergo focal fibrosis and scarring. When severe, these morphological changes result in progressive impairment of the renal function.
The aim of the present study was to assess the effects of age and low-sodium diet on the basic parameters of the renal function, i.e., glomerular filtration rate, plasma renal flow, as well as the ability of renal sodium conservation, and urinary aldosterone excretion rate in the elderly on normal and low-sodium diet.
MATERIALS AND METHODS
The study involved determination of serum and urinary values of sodium and creatinine, a 24-hour urinary aldosterone excretion rate, isotope clearence of 51Cr-EDTA and 125J-PAH in normal sodium diet (approx. 150 mmol Na+/24 h), low-sodium diet (<10 mmol Na+/24 h) over a period of 4 days. The control group (I) included 23 (11 women) healthy persons aged 18-39 (mean 30 years), and the study group (II) included 22 (10 women) healthy subjects at the age of 66-83 years (mean 73 years).
The study focused only on normotensive subjects (<140/90 mmHg) and a well-controlled cardiovascular system, with no diagnosed abnormality in the kidneys, liver and endocrine glands. Excluded from the study were also women taking any oestrogen agents over the previous 12 months. Five days prior to the inclusion into the study programme, as well as during its course, the subjects were not allowed to take any medications, also herbal preparations. In none of the subjects the serum concentrations of urea nitrogen and creatinine exceeded the upper normal limits determined by the Central Laboratory, Medical University, Gdańsk (BUN = 20 mg% – 7.14 mmol/l; creatinine = 1.3 mg% – 114.9 mmol/l). Haematocrit was 39-44%.
Serum and urinary sodium values were determined using flame photometry. Endogenic creatinine clearence was defined according to the Orłowski method. The 24-hour urinary creatinine value was also used to assess the adequacy of 24-hour urine collection. In order to eliminate inaccuracy in the urine collection for the parameters evaluated, 24-hour urinary sodium and aldosterone excretion rates were calculated per 1.0 g of the creatinine amount excreted. Urinary aldosterone was determined using radioimmune assay (CIS kits, Italy). 51Cr-EDTA clearance and 125J-hippurate clearance (PAH) were assessed conventionally following an intravenous administration of a radioactive marker. The isotope clearance was calculated from the radioactivity decay in three consecutive venous blood samples collected at different time intervals (EDTA clearance at 20 min, 40 min, 60 min; hippurate clearance at 40 min, 60 min, 120 min).
Statistical analysis was done using Student-t test and paired test.
RESULTS
Since there were no sifnificant differences between the mean values in male or female subgroups, particular groups were treated as uniform, regardless of age. Table I shows assesment of the effect of age on renal function parametres with normal sodium diet.
Results in Table 1 indicate that mean clearance values of creatinine, EDTA and PAH in the elderly were decreased at 39.5%, 38.1% and 47.0% respectively. Hence, the mean filtration rate (EDTA clearance/PAH clearance x 100) in the elderly was singificantly higher by 15.7%.
Table 2 shows a comparison of renal function parameters in the elderly on normal and low-sodium diet.
Table 2 shows that in the elderly, low-sodium diet administered for 4 days does not have any significant effect on serum sodium and creatinine, or the renal function parameters (creatinine, EDTA, hippurate clearance, filtration rate).
Table 3 provides an analysis of the effect of low sodium diet on 24 h urinary sodium excretion rate in groups I and II, as well as a comparison of mean of values of natriuria in both groups.
The data listed in Table 3 show that a 4-day low sodium diet intake results in a significantly decreased 24-hour urinary excretion in both study groups. However, the amount of 24-hour urinary sodium loss showed a higher percentage in the elderly than in the control patients (35.0% vs 14. 8%).
Table 4 includes 24-hour values of urinary aldosterone excretion in both groups on normal and low-sodium diet.
Table 4 shows that in the elderly, the basic urinary aldosterone excretion in subjects on normal sodium diet was lower by 35.8%. Low-sodium diet in young population resulted in a fourfold increase in 24-hour urinary aldosterone excretion, and a merely double rise in the elderly.
Table 1. The influence of age on serum creatinine value, glomerular filtration rate, 51Cr-EDTA clearance, renal clearance of 125 J – hippurate and filtration fraction in the control group (I) and in the elderly (II) on normal sodium diet.
| Group | serum creatinine mmol/l x ? SD | creatinine clearance ml/min/1.73
m2 x ? SD | EDTA clearance ml/min/1.73
m2 x ? SD | PAH clearance ml/min/1.73
m2 x ? SD | FF % x ? SD |
| Group I | 79.56 ? 10.60 | 124 ? 8.3 | 126 ? 5.7 | 652 ? 37 | 19.3 ? 1.4 |
| Group II | 88.40 ? 10.60 | 75 ? 4.9 | 78 ? 3.9 | 340 ? 26 | 22.9 ? 1.6 |
| p | NZ | <0.001 | <0.001 | <0.001 | <0.01 |
Table 2. Serum sodium and creatinine value, glomerular filtration rate, 51Cr-EDTA clearance, renal clearance of 125 J – hippurate and filtration fraction in the elderly on unrestricted sodium and on day 4 of sodium restriction.
| Diet | serum Na mmol/l x ? SD | serum creatinine mmol/l x ? SD | creatinine clearance ml/min/1.73
m2
x ? SD | EDTA clearance ml/min/1.73 m2
x ? SD | PAH clearance ml/min/1.73 m2
x ? SD | FF % x ? SD |
| normal sodium diet | 139.76 ? 3.31 | 99.0 ? 9.98 | 75 ? 4.9 | 78 ? 3.8 | 340 ? 26 | 22.9 ? 1.6 |
| day 4 low-sodium diet | 138.64 ? 3.42 | 106.08 ? 10.07 | 73 ? 4.2 | 76 ? 3.5 | 334 ? 27 | 22.7 ? 1.5 |
| P | NSx | NSx | NSx | NSx | NSx | NSx |
Table 3. 24 h urinary sodium excretion rate calculated on 1.0 g of creatinine in the control group (I) and in the elderly (II) on unrestricted sodium and on day 4 of sodium restriction.
| Group | 24-h urinary sodium excrection mmol/1.0 g | Paired test |
| normal sodium diet | day 4 low-sodium diet | p |
| Group I | 145.99 ? 12.71 | 21.62 ? 2.14 | < 0.001 |
| Group II | 151.61 ? 9.11 | 53.05 ? 5.58 | < 0.001 |
| P | NS | < 0.001 | |
Table 4. 24 h urinary aldosterone excretion calculated on 1.0 g of creatinine in the control group (I) and in the elderly (II) on unrestricted sodium and on day 4 of sodium restriction.
| Group | 24-h urinary aldosterone excretion on 1.0 g creatinine | Paired test |
| normal sodium diet | day 4 low-sodium diet | p |
| Group I | 6.50 ? 0.66 | 25.66 ? 2.05 | < 0.001 |
| Group II | 4.17 ? 0.40 | 8.34 ? 0.45 | < 0.001 |
| P | < 0.001 | < 0.001 | |
DISCUSSION
The results obtained in the group of clinically healthy subjects indicate significantly decreased glomerular filtration rate and plasma renal flow with conserved normal serum creatinine. Similar deviations in the renal function were also reported by other authors (1-5). The studies show definite practical implications such as the need for reduced doses of pharmacological agents which are excreted from the body mainly via the kidneys (6).
As shown in the present study, the increased filtration rate may be due to an increased intraglomerular pressure resulting from more severe atherosclerotic lesions in glomerular efferent arterioles. Mac Lachlan provides a similar interpretation of the phenomenon (7). In the 4-day course of low-sodium diet, it was not found to exert any significant effect upon controlled renal function parameters in neither study group; however, in the elderly subjects, the diet resulted in a reduced 24-hour urinary sodium loss down to 35%, whereas in the controls, the excretion rate was down to 14.81% of the initial value. The significant difference indicates an increased sodium loss in the elderly, which was also documented by Epstein and Hollenberg (8). The low-sodium diet over a short-term 4-day clinical trial did not affect the serum sodium content. The main concern, however, should be that due to defective sodium conservation, the elderly are likely to develop severely abnormal sodium metabolism resulting from a prolonged period of poor nutrition or deficient dietary sodium intake.
The elderly group on normal sodium diet was found to have their 24-hour urinary aldosterone excretion rate reduced, on average, by 35.8%. This issue has been the subject of a broad discussion in literature. Many possible causes include an impaired balance in the function of the pituitary-adrenal axis, decreased physical activity at the old age, altered beta-adrenergic function. Considering practical implications, the above is vital on assessment of aldostenuria levels in the elderly with presumed Crohn´s disease.
CONCLUSIONS
1.Clinically healthy elderly subjects on normal diet showed significantly decreased values of glomerular filtration rate, plasma renal flow, aldostenuria and increased filtration rate.
2.Low-sodium diet taken over 4 days did not exert any significant effect on the values of creatinine clearance, EDTA and hippurate; in elderly subjects, however, it resulted in a diminished ability of sodium conservation.
3.A low-sodium stimulus triggered an increase in aldostenuria, which was, however, lower in the elderly persons as compared with a control group of young people.
Piśmiennictwo
1. Bohler J. et al.: Renal functional reserve in elderly patients. Clin. Nephrol. 1993; 39:145-50. 2. Epstein M.: Aging and the kidney. J. Am. Soc. Nephrol. 1996; 7:1106-22. 3. Fliser D. et al.: Renal reserve in the elderly. Semin. Nephrol. 1995; 15:463-7. 4. Fliser D. et al.: Renal functional reserve in healthy elderly subjects. J. Am. Soc. Nephrol. 1993; 3:1371-7. 5. Mimran A. et al.: Aging and sodium homeostasis. Kidney Int. 1992; 37 Suppl.: S107-13. 6. Simon S.R., Gurwitz J.H.: Drug therapy in the elderly: Clin. Pharmacol. Ther. 2003; 73:387-93. 7. Mc Lachlan M.S.F.: The ageing kidney. Lancet 1978; 2:143-5. 8. Epstein M., Hollenberg N.K.: Age as a determinant of renal sodium conservation in normal man. J. Lab. Clin. Med. 1976; 87:411-7.
