International Urology and Nephrology

, Volume 42, Issue 1, pp 273–277

Fractional excretion of K, Na and Cl following furosemide infusion in healthy, young and very old people

Authors

    • Nephrology DivisionHospital Italiano de Buenos Aires
  • Juliana Reynaldi
    • Nephrology DivisionHospital Italiano de Buenos Aires
  • Manuel Vilas
    • Nephrology DivisionHospital Italiano de Buenos Aires
  • Raul De Miguel
    • Laboratory DivisionHospital Italiano de Buenos Aires
  • Nora Imperiali
    • Nephrology DivisionHospital Italiano de Buenos Aires
  • Luis Algranati
    • Nephrology DivisionHospital Italiano de Buenos Aires
Nephrology - Original Paper

DOI: 10.1007/s11255-009-9547-8

Cite this article as:
Musso, C.G., Reynaldi, J., Vilas, M. et al. Int Urol Nephrol (2010) 42: 273. doi:10.1007/s11255-009-9547-8
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Abstract

Furosemide test is a simple and useful test of renal physiology used to evaluate the capability of the collecting ducts to secrete potassium under the effect of serum aldosterone. Its behaviour pattern has been established in children and young adults but not described in very old healthy people, which we explored in this study.

Material and methods

Twenty-six healthy volunteers on a standard Western diet (50 mmol of K/day) were studied: 20 of them were young (between 17 and 40 years old) and the rest were very old (between 75 and 85 years old). They suffered from no diseases and were not on any medication. Before, during the test and 180 min after a single dose of intravenous furosemide (1 mg/kg), urine and blood samples were obtained for creatinine and electrolytes levels. From these data we calculated fractional excretion (FE) of electrolytes; serum aldosterone was measured pre and post furosemide infusion. Statistical analysis was performed by applying Student’s t-test.

Results

There was no significant difference regarding pre-furosemide (basal) FE of potassium between the very old and young group. Post-furosemide average FE of potassium was significantly lower in the very old group (27.4 ± 2%) compared with the young group (35.4 ± 9%) (P = 0.04). Even though there was no significant difference in post-furosemide peak FE of potassium value, it was reached later in the very old (120 min) compared with the young (30 min). Serum aldosterone levels were significantly higher post furosemide in both groups: 18.3 ± 12.2 ng/dl (pre) versus 32.5 ± 18.6 ng/dl (post) in the young (P = 0.007) and 69.8 ± 13.7 ng/dl (pre) versus 113.3 ± 54.8 ng/dl (post) in the very old (P = 0.04). Furthermore, all serum aldosterone values (pre and post furosemide) were significantly higher in very old people compared with young people (P < 0.001). Basal fractional excretion of sodium and chloride were slightly higher in the very old group compared with the young group (P = 0.05). Average post-furosemide FE of sodium and chloride were slightly and significantly lower in the very old (P = 0.05 and P = 0.03), respectively. However, there was no significant difference in peak post-furosemide FE of sodium and chloride values, which were reached later in the very old (120 min) compared with the young (30 min).

Conclusion

Furosemide test showed a significantly lower average post-furosemide FE of potassium value, delayed post-furosemide peak FE of Na, K and Cl and a hormonal pattern of aldosterone resistance in very old people.

Keywords

Furosemide testOldest oldPotassium

Introduction

Furosemide test is a simple and useful renal test to evaluate the ability of the collecting tubules to secrete potassium induced by serum aldosterone secretion secondary to furosemide infusion [1]. Its pattern in healthy children and young persons has already been described, but it has not been defined in very old healthy persons, who are an important target to study regarding this test because it is known that renal physiology differs in healthy old people compared with young people [2]. We hypothesized that furosemide test could have a modified normal pattern in the very old.

Materials and methods

Twenty-six healthy volunteers on a standard sodium and potassium western diet (50 mmol of K/day) were studied: 20 of them were young (between 17 and 40 years old) and 6 were very old (older than 75 years old).

They suffered from no diseases and were not on any medication. Their serum urea, creatinine, electrolytes and renal ultrasound were normal. The furosemide test consisted of the following protocol: At 8 a.m. a basal blood and urinary sample (time zero) were taken from a fasting volunteer, and after that a single dose of intravenous furosemide (1 mg/kg) was administered. Then, a sample was taken from every micturition until the test ended at 180 min. Blood samples were also taken pre furosemide administration (time zero), and post furosemide, at 90 and 180 min (end of the test). Blood pressure was also measured throughout the test, every 30 min. Since the results are expressed as fractional excretion of the studied substances, levels of potassium, sodium, chloride and creatinine were measured from the obtained blood and urinary samples in order to calculate their fractional excretion values. From all these fractional excretion data, we obtained the basal value (pre furosemide infusion: time zero), the average post-infusion value (mean value of the post-furosemide samples), and the peak value (highest value post furosemide infusion) of each electrolyte (potassium, sodium and chloride). Fractional excretion was calculated applying the following formula [3]:
$$ ( {\text{urinary }}\alpha /{\text{plasma }}\alpha ) \times \left( {\text{plasma creatinine/urinary creatinine}} \right) \times 100, $$
where α is the concentration of sodium, chloride or potassium.

Serum aldosterone was measured from two blood samples: time zero (pre furosemide infusion) and 180 min after furosemide administration.

All individuals remained fasting during the duration of the test. At the end of the test, in order to avoid complications secondary to dehydration, the amount of urine volume passed was replaced, half of it intravenously (normal saline) and the rest with tap-water per os.

All the studied substances were measured by chemical autoanalyzer Beckman LX20, except for serum aldosterone, which was measured by direct radioimmunoassay [Diagnostic System Laboratories (DSL) Inc.].

Statistical analysis was performed applying Student’s t-test.

None of the volunteers had any contraindication to participate in a furosemide test, such as hypotension, hypokalemia, dehydration or allergy to sulfa-drugs, and they signed a consent form approved by the Hospital’s Institutional Review Board.

Results

Basal fractional excretion (FE) of potassium (pre furosemide infusion) was not significantly different between the groups, while post-furosemide infusion average fractional excretion of potassium was significantly lower in the very old group compared with the young group: 27.4 ± 2% (very old) versus 35.4 ± 9% (young), P = 0.04 (Table 1). Post-furosemide infusion peak fractional excretion of potassium was not significantly different between the groups (Table 1). However, this peak value was reached later in the very old compared with the young persons: at 120 min versus 30 min, respectively.
Table 1

Fractional excretion of electrolytes (%) in furosemide test

 

FEK (young) X ± SD

FEK (very old) X ± SD

 

Basal value

11.5 ± 5

11.1 ± 4

NS

Peak value

31.6 ± 11

39.8 ± 8

NS

Average value

35.4 ± 9

27.4 ± 2

0.04

 

FENa (young) X ± SD

FENa (very old) X ± SD

P

Basal value

0.7 ± 1

1.2 ± 1

0.05

Peak value

7.8 ± 4

8.2 ± 1

NS

Average value

8.4 ± 3

5.5 ± 1

0.05

 

FECl (young) X ± SD

FECl (very old) X ± SD

 

Basal value

1.1 ± 1

1.7 ± 1

0.05

Peak value

11.6 ± 6

11.5 ± 1

NS

Average value

12.6 ± 5

7.8 ± 1

0.03

FEK fractional excretion of potassium, FENa fractional excretion of sodium, FECl fractional excretion of chloride, SD standard deviation, NS not significant

Table 2

Absolute excretion of electrolytes in furosemide test

 

Young X ± SD

Very old X ± SD

P

Total urinary potassium excretion (mmol/test)

30.6 ± 9

9.9 ± 2

0.03

Total urinary sodium excretion (mmol/test)

254 ± 4

69.3 ± 1

0.02

Total urinary chloride excretion (mmol/test)

272.2 ± 5

70.2 ± 1

0.02

Post-furosemide infusion serum aldosterone levels were significantly higher than the pre-furosemide infusion values in both groups: 18.3 ± 12.2 ng/dl (pre) versus 32.5 ± 18.6 ng/dl (post) in the young (P = 0.007) and 69.8 ± 13.7 ng/dl (pre) versus 113.3 ± 54.8 ng/dl (post) in the very old (P = 0.04) (Table 3). All serum aldosterone values (pre- and post-furosemide ones) were significantly higher in the very old persons compared with young persons (P < 0.001) (Table 4).
Table 3

Serum aldosterone level (ng/dl) pre furosemide (0) and post furosemide administration (1) in young and very old group

Young

Serum aldosterone 0

Serum aldosterone 1

X

18.3

32.5

SD

12.2

18.6

P

0.007

 

Very old

Serum aldosterone 0

Serum aldosterone 1

X

69.8

113

SD

13.7

54.8

P

0.04

 
Table 4

Delta serum aldosterone pre furosemide (0) and post furosemide (1) between very old and young people

 

Very old

Young

Delta

P

Serum aldosterone (0) (ng/dl)

69.8 ± 13.7

18.3 ± 12.2

−14.2

<0.001

Serum aldosterone (1) (ng/dl)

113.3 ± 54.8

32.5 ± 18.6

80.8

<0.001

Basal FE of sodium and chloride were slightly higher (P = 0.05) in the old group (Table 1). Post-furosemide infusion average fractional excretion of sodium and chloride were slightly and significantly lower in the very old group compared with the young group as follows: FE of sodium, 5.5 ± 1% (very old) versus 8.4 ± 3% (young) P = 0.05; FE of chloride, 7.8 ± 1% (very old) versus 12.6 ± 5% (young) P = 0.03 (Table 1). Post-furosemide infusion peak fractional excretion of sodium and chloride were not significantly different between the groups (Table 1). However, both post-furosemide peaks (sodium and chloride) were reached later in the very old compared with the young persons: at 120 min versus 30 min, respectively. Additionally, total urinary potassium, sodium and chloride excretions achieved during the whole test were significantly lower in the very old group compared with the young group (Table 2).

Discussion

Fractional excretion of potassium, was not significantly different in either basal (pre furosemide) or in post-furosemide peak values between the age groups. However, the post-furosemide average fractional excretion of potassium was significantly lower in the very old compared with the young (Table 1). This finding can be explained by the reduced potassium excretion capability characteristic of older people [46]. Finally, the post-furosemide peak fractional excretion of potassium was reached later in the very old persons (at 120 min) versus the young (30 min).

Urinary potassium excretion is increased post furosemide infusion in the young, primarily because of the increase in sodium delivery to the collecting ducts, which stimulates sodium reabsorption, electronegative luminal charge and consequently potassium secretion. Besides, furosemide also increases urinary potassium secretion by inducing a hypovolemic state which stimulates aldosterone release and consequently potassium secretion [79]. The reduced urinary potassium excretion capacity observed in the elderly has been attributed to a lower plasma aldosterone level or to a lower distal tubular response to this hormone (aldosterone resistance) [46]. In our study, pre- and post-furosemide administration aldosterone levels were significantly higher in the very old group compared with the young group (Table 4). Besides, in both age groups, there was a significant increase in serum aldosterone level after intravenous administration of furosemide (Table 3). All these findings (of higher serum aldosterone levels without higher urinary potassium excretion in the very old group) suggest an aldosterone resistance state and this has been proposed as the physiopathological mechanism of the reduced urinary potassium excretion that is usually observed in the elderly [46]. In this study slightly higher basal (pre-furosemide) fractional excretion of sodium and chloride was documented in the very old group (P = 0.05). This phenomenon reflects the high sodium urinary loss typical of this group, which is mainly secondary to an impairment in the reabsorption of this cation in the thick ascending loop of Henle [10, 11]. Regarding the documented slightly lower post-furosemide average fractional excretion of sodium (P = 0.05) and significantly lower post-furosemide average FE of chloride (P = 0.03) in the very old, this phenomenon could be interpreted as a consequence of a lower tubular response (sodium and chloride loss) to furosemide in these people, whose altered ascending loop of Henle function avoids a better diuretic response (Table 2) [7].

Finally, there was no significant difference in the post-furosemide peak value of the fractional excretion of sodium and chloride between the very old and the young, except for a delayed peak response in the former: at 120 min and 30 min, respectively. This finding is in agreement with other renal physiological responses, such as renal acidification, which have been found not to be reduced but delayed in the healthy elderly [2].

Fractional excretion of potassium, sodium and chloride (basal, peak and average values) were studied in children (6–15 years old) by Rodriguez-Soriano et al., who found that values in healthy children were similar to those in healthy adults [12].

A limitation of this study is that the number of very old volunteers studied was small; it should be taken into account however that population of healthy very old persons not receiving any medication is difficult to find.

Conclusion

Furosemide test showed a significant lower average post-furosemide FE of potassium value, delayed post-furosemide peak and a hormonal pattern of aldosterone resistance in very old people.

Acknowledgements

The authors wish to thank the Epidemiology Division of the Internal Medicine Department—Hospital Italiano de Buenos Aires for its help in the statistical analysis of this trial

Copyright information

© Springer Science+Business Media, B.V. 2009