Renal Prostaglandins, Effective Renal Plasma Flow and Glomerular Filtration Rate in Healthy Elderly Subjects A. ASOKAN, G. J. FANCOURT, S. E. BENNETT, C. M. CASTLEDEN
Summary This study tests the hypothesis that the age-associated reduction in glomerular filtration rate (GFR) and the presence of glomerulosclerosis renders effective renal plasma flow (ERPF) prostaglandin dependent. Ten healthy elderly volunteers were studied in a single-blind placebo-controlled manner using indomethacin to suppress the renal prostaglandins. There was no significant difference in ERPF or GFR following indomethacin when compared with placebo. These results suggest that blocking renal prostaglandins does not significantly alter ERPF or GFR in healthy elderly people.
Introduction Renal prostaglandins do not contribute to the maintenance of effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in healthy young people. However, in hypovolaemic states and in chronic renal parenchymal disease these substances play a role in the maintenance of both. Prostaglandins are unsaturated fatty acid compounds derived from the precursor arachidonic acid. They are ubiquitous in distribution and act as local hormones [1]. The kidney is extremely active in the synthesis and metabolism of prostaglandins, the major ones being PGE2, PGI2 and PGF2 [2]. These prostaglandins have a role in maintaining ERPF and GFR and in regulating renin release, water excretion and sodium and potassium metabolism [3]. Renal prostaglandins do not contribute to the maintenance of ERPF and G R F in healthy young people [4-6]. However, in hypovolaemic states where there is activation of the renin-angiotensin system, renal vasoconstric-
tion is mitigated by the simultaneous stimulation of vasodilatory prostaglandins [1], and renal blood flow (RBF) and GFR are thus maintained. Examples of such clinical states are volume depletion, congestive cardiac failure, cirrhosis (particularly with ascites) and the nephrotic syndrome. Although not necessarily characterized by hyper-reninaemia, chronic renal parenchymal disease represents a situation in which active renal prostaglandin production may maximize RBF and GFR in surviving nephrons [3]. It has been stated that ageassociated reduction in GFR and glomerulosclerosis may make RBF prostaglandin dependent in elderly people [7, 8]. This hypothesis was tested in the present study. Methods Ten healthy volunteers (seven women and three men) were included in a single-blind placebo-controlled study. The mean age was 70.5 years (range 65-80). None had been taking any drugs for at least 6 months prior to the study. The study was approved Age tnd Ageing 1992;21:39-42
A. ASOKAN ET AL.
4°
by the Leicestershire Health Authority ethical committee. All participants gave informed consent and were assessed by the renal dietician to ensure an adequate sodium intake (at least 100 mmol/24 h) prior to the study. Blood pressure, body weight, urinary prostaglandins, ERPF and GFR were measured at baseline and after one week's administration of placebo (one capsule three times a day). Indomethacin (25 mg three times a day) was given for a week and all the measurements were repeated. ERPF and GFR were estimated using I-125-labelled Hippuran and Cr-52-labelled EDTA, respectively [9]. After a single injection of the isotopes, venous blood samples were taken every 10 min during the first hour and then hourly for the next 3 hours. Urinary prostaglandins (6-keto-PGFl-alpha and thromboxane-B2) were measured by radio-immunoassay using the Du Pont RIA kit. Statistically significant differences were sought between the three groups using two-tailed ANOVA analysis (placebo vs baseline vs indomethacin). A paired Student's t test was used to seek significant differences between two groups.
Results There was no significant change in body weight following indomethacin or placebo. There was a significant fall in blood pressure between baseline and placebo but not between placebo and indomethacin (Table I), this probably represents the fall in blood pressure with repeated measurement. Urinary levels of 6-keto PGF1 -alpha a metabolite of PGI2 was significantly suppressed following indomethacin (p < 0.05) but not following placebo. Urinary thromboxane-B2 showed a small but nonsignificant decrease following indomethacin
Table II. Mean ( ± SEM) urinary prostaglandin excretion before (pre) and following (post) administration of placebo and indomethacin in healthy elderly volunteers Placebo
Indomethacin
6-Keto PGF1-alpha (pg/ml) Pre 399 (49.24)
397 (47.63)
389(30.13)
Post
324 (24.59)
Thromboxane-B2 (pg/ml) Pre 151.8(10.21) Post 186.9(18.71)
170.4(12.54) 149.1 (8.15)
•p
Summary This study tests the hypothesis that the age-associated reduction in glomerular filtration rate (GFR) and the presence of glomerulosclerosis renders effective renal plasma flow (ERPF) prostaglandin dependent. Ten healthy elderly volunteers were studied in a single-blind placebo-controlled manner using indomethacin to suppress the renal prostaglandins. There was no significant difference in ERPF or GFR following indomethacin when compared with placebo. These results suggest that blocking renal prostaglandins does not significantly alter ERPF or GFR in healthy elderly people.
Introduction Renal prostaglandins do not contribute to the maintenance of effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) in healthy young people. However, in hypovolaemic states and in chronic renal parenchymal disease these substances play a role in the maintenance of both. Prostaglandins are unsaturated fatty acid compounds derived from the precursor arachidonic acid. They are ubiquitous in distribution and act as local hormones [1]. The kidney is extremely active in the synthesis and metabolism of prostaglandins, the major ones being PGE2, PGI2 and PGF2 [2]. These prostaglandins have a role in maintaining ERPF and GFR and in regulating renin release, water excretion and sodium and potassium metabolism [3]. Renal prostaglandins do not contribute to the maintenance of ERPF and G R F in healthy young people [4-6]. However, in hypovolaemic states where there is activation of the renin-angiotensin system, renal vasoconstric-
tion is mitigated by the simultaneous stimulation of vasodilatory prostaglandins [1], and renal blood flow (RBF) and GFR are thus maintained. Examples of such clinical states are volume depletion, congestive cardiac failure, cirrhosis (particularly with ascites) and the nephrotic syndrome. Although not necessarily characterized by hyper-reninaemia, chronic renal parenchymal disease represents a situation in which active renal prostaglandin production may maximize RBF and GFR in surviving nephrons [3]. It has been stated that ageassociated reduction in GFR and glomerulosclerosis may make RBF prostaglandin dependent in elderly people [7, 8]. This hypothesis was tested in the present study. Methods Ten healthy volunteers (seven women and three men) were included in a single-blind placebo-controlled study. The mean age was 70.5 years (range 65-80). None had been taking any drugs for at least 6 months prior to the study. The study was approved Age tnd Ageing 1992;21:39-42
A. ASOKAN ET AL.
4°
by the Leicestershire Health Authority ethical committee. All participants gave informed consent and were assessed by the renal dietician to ensure an adequate sodium intake (at least 100 mmol/24 h) prior to the study. Blood pressure, body weight, urinary prostaglandins, ERPF and GFR were measured at baseline and after one week's administration of placebo (one capsule three times a day). Indomethacin (25 mg three times a day) was given for a week and all the measurements were repeated. ERPF and GFR were estimated using I-125-labelled Hippuran and Cr-52-labelled EDTA, respectively [9]. After a single injection of the isotopes, venous blood samples were taken every 10 min during the first hour and then hourly for the next 3 hours. Urinary prostaglandins (6-keto-PGFl-alpha and thromboxane-B2) were measured by radio-immunoassay using the Du Pont RIA kit. Statistically significant differences were sought between the three groups using two-tailed ANOVA analysis (placebo vs baseline vs indomethacin). A paired Student's t test was used to seek significant differences between two groups.
Results There was no significant change in body weight following indomethacin or placebo. There was a significant fall in blood pressure between baseline and placebo but not between placebo and indomethacin (Table I), this probably represents the fall in blood pressure with repeated measurement. Urinary levels of 6-keto PGF1 -alpha a metabolite of PGI2 was significantly suppressed following indomethacin (p < 0.05) but not following placebo. Urinary thromboxane-B2 showed a small but nonsignificant decrease following indomethacin
Table II. Mean ( ± SEM) urinary prostaglandin excretion before (pre) and following (post) administration of placebo and indomethacin in healthy elderly volunteers Placebo
Indomethacin
6-Keto PGF1-alpha (pg/ml) Pre 399 (49.24)
397 (47.63)
389(30.13)
Post
324 (24.59)
Thromboxane-B2 (pg/ml) Pre 151.8(10.21) Post 186.9(18.71)
170.4(12.54) 149.1 (8.15)
•p
