l. The effect of age and sex on glomerular filtration rate (GFR) was measured by the 51Cr-EDTA radioisotopic method in 76 normal individuals (43 women and 33 men). 2. Age has a significant effect on GFR. Subjects aged 41 to 60 years have GFR values [104.5 ± 16.5 ml min"1 (1.73 m2)" 1 , N- 43]lower than younger individuals aged 20 to 40 years [116.6 ± 11.2 ml min"1 (1.73 m2 )" 1 , N- 33]. GFR decreases after 40 years of age by approximately 6.0 ml min"1 (1.73 m2)"1 per decade. 3. GFR values in women [105.9 ± 16.0 ml min" 1 (1.73 m2)" 1 , N- 43] were lower when compared to men [114.8 ± 14.3 ml min"1 (1.73 m2)" 1 , N = 33]. 4. We conclude that the effect of sex and age must be taken into account when establishing reference values for GFR

Azevedo, Mirela Jobim de

Friedman, Rogério

Gross, Jorge Luiz

Pecis, Miriam

Silveiro, Sandra Pinho

Brazilian Journal of Medical and Biological Research

English

Lume 5.8

BrazilianJ Med Bioi Res (1992) 25: 129-134 ISSN 0100-879X EFFECT OF AGE AND SEX ON GLOMERULAR FILTRATION RATE MEASURED BY 51 Cr-EDTA J:L. GROSS, R. FRIEDMAN, M.J. AZEVEDO, S.P. SILVEIRO and M. PECIS Serviro de Endocrinologia, Hospital de CUnicas de Porto Alegre, 90210 Porto Alegre, RS, Brasil l. The effect of age and sex on glomerular filtration rate (GFR) was measured by the 51Cr-EDTA radioisotopic method in 76 normal individuals (43 women and 33 men). 2. Age has a significant effect on GFR. Subjects aged 41 to 60 years have GFR values [104.5 ± 16.5 ml min"1 (1.73 m2)" 1, N- 43]lower than younger individuals aged 20 to 40 years [116.6 ± 11.2 ml min"1 (1.73 m2 )" 1, N- 33]. GFR decreases after 40 years of age by approximately 6.0 ml min"1 (1.73 m2)" 1 per decade. 3. GFR values in women [105.9 ± 16.0 ml min" 1 (1.73 m2)"1, N- 43] were lower when compared to men [114.8 ± 14.3 ml min"1 (1.73 m2)"1, N = 33]. 4. We conclude that the effect of sex and age must be taken into account when establishing reference values for GFR. Key words: glomerular filtration rate, age, sex. Introduction Accurate measurement of glomerular filtration rate (GFR) is essential for the early diagnosis and follow-up of patients with renal disease or after kidney transplan-tation. In order to correctly interpret changes in GFR due to renal diseases the effect of sex and age should be taken in account. The influence of age on GFR has been clearly established and several studies have demonstrated a decrease in renal function particularly after 40 or 50 years of age (Davies and Shock, 1950; Rowe et al., 1976; Slack and Wilson, 1976; Granerus and Aurell, 1981; Morrison et al., 1983). However, there are few but contradictory data about the effect of sex on GFR in human subjects. It is commonly believed that men normally have a slightly higher GFR than women (Wesson, 1969), although some investigators (Slack and Wilson, 1976; Granerus and Aurelf, 1981) did not observe sex differences. The objective of the present study was to determine the influence of sex and age on GFR measured by the single 51 Cr-EDTA injection technique in men and women aged 20 to 60 years. Research supported in part by Fundo de Incentive a Pesquisa do HCPA and CNPq (No. 504029/88-6). M.J.A., S.P.S. and M.P. are recipients of CAPES fellowships. . Correspondence: Dr. J.L. Gross, Grupo de Pesquisa e P6s-gradua~iio, Hospital de Clinicas de Porto Alegre, Rua Rami..ro Bar.celos, 2350,90210 Porto Alegre, RS, Brasil. . 130 J.L. Grosset a/. Subjects and Methods Subjects Seventy-six healthy volunteers (43 females and 33 males), with a body mass index <30 kg/m2 and not on drug treatment were studied. These individuals did not have a family history of diabetes mellitus, were normotensive according to WHO criteria and did not present abnormalities in routine biochemical tests. The age range was 20 to 60 years, and females and males were grouped at 10-year intervals. Informed consent was obtained from each individual. The study protocol was approved by the Ethics Committee of the Hospital. Glomerular filtration rate The procedure was performed at 8:00 a.m. after an overnight fast. GFR was measured by the technique described by Chantler and Barratt (1972). A single bolus of 5.55 MBq 51 Cr-EDTA (Instituto de Pesquisas Energeticas e Nucleares, Sao Paulo, Brazil) was injected into the cubital vein on the forearm and blood samples were taken from the opposite arm 2, 3 and 4 h later for measurement in a gamma-counter. The activity of each sample (in log cpm) was plotted against time and a monoexponentialline fitted by linear regression. This allows a microcomputer calculation of GFR which was corrected to 1.73 m2 body surface area. For four subjects, GFR measurement was repeated on three additional occasions in order to obtain the mean intra-individual coefficient of variation. Statistical analysis Parametric tests were used because the GFR values presented a normal distribu-tion. The results were expressed as mean ± SD. GFR data were analyzed by two-way ANOV A, taking into consideration 2 factors, i.e., sex and age. The independent effect of age on GFR was analyzed by one-way ANOV A and the differences between the age groups were further analyzed by the multiple comparison test (Student-Newman-Keuls test). Differ-ences in GFR between sexes were analyzed by the F test. The level of significance for statistical analysis was set at P<0.05. Results The GFR values for men and women of different ages are presented in Table 1 and Figure 1. The mean intra-individual coefficient of variation was 12%. Age had a significant effect on GFR (F = 4.4749, P = 0.0061), and the multiple comparison test demonstrated that the GFR values for subjects aged 50 to 60 years were significantly lower (P<0.05) than those for individuals aged 20 to 30 and 31 to 40 years. There was no difference Brazilian J Med Bioi Res 25(2) 1992 Effect of age and sex on glomerular fi ltration rate 131 between subjects aged 20 to 30 and 31 to 40 years and between subjects aged 31 to 40 and 51 to 60 years. The GFR values of sub-jects aged 41 to 50 years were not different from those for the other groups, but since there was a clear Table 1- Effect of age and sex 011 glomerular filtration rate ofnormal individuals measured by the stcr-EDTA single-i11jectionmethod. Data are reported as means± SD in ml min' 1 (1.73 m2r 1 for the number of normal individuals given in parentheses. *P<0.05 compared to ages 20-30 and 31-40 (ANOVA, Student-Neuman-Keuls test). Sex 20-30 114.8± 11.1 (10) trend to reduction in this Men group and the values ob-served were quite similar Women 115.8 ± 14.0 to those of the subjects (8) aged 51 to 60 years, it was arbitrarily decided to se-Age (years) 31-40 123.4 ± 12.3 (6) 114.7 ± 11.0 (9) 41-50 113.9 ±15.6 (8) 101.5 ± 15.8 (12) 51-60 109.7 ± 16.9* (9) 98.3 ±15.5* (14) lect two age subgroups: 20 to 40 and 41 to 60 years. The GFR of the younger individuals was higher than that of the older group (116.6 ± 11.2 ml min· 1 (1.73 m2)·1 vs 104.5 ± 16.5 rn1 min·1 (1.73 m2)'1, P = 0.001). This means that GFR decreases after 40 years of age, in both men and women, by approximately 6.0 ml min·1 (1.73 m2)'1 per decade. In the group as a whole, the GFR was lower in women when compared to men (105.9 ± 16.0 ml min· 1 (1.73 m2)' 1 vs 114.8 ± 14.3 ml min·1 (1.73 m2)'1, p = 0.014). This difference was more evident after 30 years of age, although comparison of the GFR of men and women in the four age sub-groups taken individually did not achieve statistical significance. In the two-way ANOVA, age group and sex did not interact (F = 0.841, P = 0.47), thus confirming their independent effects on GFR. A simplified table for reference values of 51 Cr-EDTA GFR constructed from these data for routine clinical use is presented in Table 2. Discussion The effect of age on GFR was confirmed in the present study. A reduction rate of 6 mljmin per decade observed after 40 years of age is in agreement with a previously reported rate of around 4 ml/min per decade before 50 years and of 10 mlfmin per decade thereafter (Granerus and Aurell, 1981). Davies and Shock (1950) using inulin clearance in 70 males aged 24 to 89 years, observed that the GFR of men 80 to 90 years of age is approximately half of that of men 20 to 30 years old. This reduction was also more evident ( after 50 years of age. On the other hand, Slack and Table 2- Simplified normal reference values for glomerular filtration rate measured by the single 51 Cr-EDTA injection technique. Data are reported as means ± SD in ml miJ11 (1.73 m2r 1 for the number of normal indi-viduals given in parentheses. Data taken from Table l. *P<0.05 compared to ages 20-40 (Student t-test) . Age (years) Sex 20-40 41-60 Men 118.0 ± 12.0 111.7 ± 16.0* (16) (17) Women 115.2 ± 12.1 99.8 ± 15.4* (17) (26) Brazilian} Med Bioi Res 25(2) 1992 132 J.L. Grosset al. 0 140 • • • • 0 • 0 130 0 • • • • • "';" 120 ,-.. N e ..., r-; -'-' "';" 110 = "§ • .! • I CD • " • '"' ~ 100 • • < 0 ~ 0 "' • • .. • 0 u - 90 0 1/") • 0 0 0 0 80 0 70 0 J ,........-, r---1 r---1 r---1 L 20 30 31 40 41 50 51 60 AGE (years) Figure 1 - pistribution of glomerular filtration rates as a function of age and sex of normal subjects. GFR was determined by the 51Cr-EDTA single-injection method. Data are reported for women (e, N = 43) and men (0, N = 33) "for the age groups given on the absc.issa. The lines connect the mean values for each group. Brazilian J Med Bioi Res 25(2) 1992 Effect of age and sex on glomerular filtration rate 133 Wilson (1976), studying 141 healthy renal transplant donors, observed a linear age-related decline in inulin clearance of 4 rnl/min per decade beginning in the 20's. These authors were unable to demonstrate a remarkable fall in renal function in the 40- to 60-year age group. The decline in GFR may be related to several physiologic and pathologic changes seen in the aging kidney. A progressive reduction in renal plasma flow occurs simultaneously with the decrease in GFR (Slack and Wilson, 1976). Factors contributing to this decreased renal plasma flow include an age-related decline in cardiac output and reductions in the renal vascular bed (Rowe et al., 1976). The elastic layers of small arteries becomes thicker and reduplicated, encroaching on the lumen and the average size of nephrons diminishes (Morrison et al., 1983). Furthermore, Kaplan et al. (1975) observed a substantial increase in the number of sclerotic glomeruli after the age of 50. The effect of sex on GFR is still unsettled. The observed results revealed a 10% decrease in women's GFR values when compared with men's values. These data are in accordance with series reported by Wesson (1969). This investigator summarized the data combined from different laboratories supporting the view that GFR measured by inulin clearance is significantly higher in men than in women at any age. Experimental studies in Munich-Wistar rats also confirmed a sex difference in GFR (Munger and Baylis, 1988; Remuzzi et al., 1988). The lower GFR values observed in female rats are due to a greater vascular resistance in females than ill males probably related to the effect of ovarian hormones on renal hemodynamics (Munger and Baylis, 1988). However, a sex effect on the GFR of human beings has not been confirmed by others. Slack and Wilson ( 1976), studying GFR measured by inulin clearance, did not observe any sell. difference. Landahl et al. ( 1981) also did not observe differences in GFR measured by 51 Cr-EDTA between 40 men and 32 women 70 to 75 years old . In conclusion, the present data confirm that GFR decreases with age and that the women's values are lower than men's. These factors must be taken in account when establishing reference values. References Chantler C & Barrat TM (1972). Estimation of glomerular filtration rate from plasma clearance of 51-chromium edetic acid. Archives of Diseases of Childhood, 47: 613-617. Davies DF & Shock NW (1950). Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. Journal of Clinical Investigation, 29: 496-507. Graneros G & Aurell M (1981). Reference values for 51 Cr-EDTA clearance as measure of glomerular filtration rate. Scandinavian Journal of Clinical and Laboratory Investigation, 41: 611-616. Kaplan C, Paternack B, Shah H & Gallo G (1975). Age related incidence of sclerotic glomeruli in human kidneys. American Journal of Pathology, 80: 227-234. Landahl S, Aurell M & J agenburg R (1981). Glomerular filtration rate at age 70 and 75. Journal of Clinical and Experimental Gerontology, 3: 29-45. Morrison RBI, Davison JM & Kerr DNS (1983). Clinical physiology of the kidney: tests of renal function and structure. In: Wheatheral DJ, LedinghamJGG & Warrel DA (Editors). OxfordTextbookofMedicine. University Press, Oxford, 18.17-18.18. Munger K & Baylis C (1988). Sex differences in renal hemodynamics in rats. American Journal of Physiology, 254 (Renal Fluid Electrolyte Physiology), 23: F223-F231. BrazilianJ Med Bioi Res 25(2) 1992 134 J.L. Grosset a/. Remuzzi A, Puntorieri S, Mazzoleni A & Remuzzi G (1988). Sex related differences in glomerular ultrafiltration and proteinuria in Munich-Wistar rats. Kidney Imemarional, 34: 481-486. RoweJW, Andres R, Tobin JD, Norris All & Shock NW (1976). The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. Joumal of Gerontology, 31: 155-163. Slack TK & Wilson BM (1976). Normal renal function. Cin and CPAH in healthy donors before and after nephrectomy. Mayo Clinic Proceedings, 51: 296-300. Wesson Jr LG (1969). Renal hemodynamics in physiological states. In: Physiology of the Human Kidney. Grune and Stratton, New York, 96-108. Brazi/ianJ Med Bioi Res 25(2) 1992 Received February 25, 1991 Accepted January 9, 1992 

Effect of age and sex on glomerular filtration rate measured by 51Cr-EDTA

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Effect of age and sex on glomerular filtration rate measured by 51Cr-EDTA

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