Annals of the Rheumatic Diseases, 1978, 37, 333-338
The relationship between uric acid and potassium in normal subjects ALASTAIR C. KENNEDY, KEITH BODDY, PRISCILLA C. KING, JENNIFER BRENNAN, JOHN A. ANDERSON, AND W. WATSON BUCHANAN From the Centre for Rheumatic Diseases, University Department of Medicine, Royal Infirmary, Glasgow; Scottish Universities Research and Reactor Centre, East Kilbride; and Department of Biomathematics, University of Oxford, Oxford, England SUMMARY The serum uric acid concentration in normal healthy subjects has been studied in relation to sex, height, weight, lean body mass measured from total body potassium and predicted from the Hume-Weyers formula (1971), total body potassium, plasma potassium and urea, and packed cell volume. The strongest correlation was found with sex, but height, weight, total body potassium, lean body mass (measured and predicted) also correlated significantly with serum uric acid concentration. However, when the sex variable was removed, the other factors lost their significant correlation. Finally, total red blood cell and plasma volumes were predicted (Hume and Goldberg, 1964) and from these an estimate of total plasma uric acid, total plasma potassium, and total red blood cell potassium obtained. Measured total body potassium was found to correlate well with total plasma potassium and total red blood cell potassium independent of sex. Total plasma uric acid correlated well with measured total body potassium when both sexes were considered and when separated into male and female groups the males retained a significant correlation as did the female group.
Serum uric acid concentrations, although subject in relationships to serum uric acid concentration (Evans the individual to marked fluctuation, are distributed et al., 1968). Evans et al. (1968) found that ponderal unimodally in large scale population studies index bore a slightly better relationship to serum (Mikkelsen et al., 1965) and it would seem from uric acid than did body weight, but the relative twin studies that the major determinant of serum importance of body fat or lean body mass in uric acid levels are environmental rather than determining serum uric acid has never been fully genetic (Boyle et al., 1967). Several contributing explored. factors, in addition to dietary intake, have been In the present report, serum uric acid has been studied; haemoglobin concentration and alcohol studied in relation to lean body mass, as represented consumption (Evans et al., 1968) and psychological by direct measurements of total body potassium, traits (Brooks and Mueller, 1966; Kasl et al., 1966) similarly the relationship of total body potassium to have all been reported to be related to the serum parameters of blood potassium have been inuric acid concentration. vestigated. That serum uric acid and body bulk are interrelated has been documented in several races with a Materials and methods variety of geographic, ethnic, and demographic characteristics (Dunn et al., 1963; Prior et al., 1964; SUBJECTS Mikkelsen, 1965; Mikkelsen et al., 1965; Acheson Fifty-seven normal healthy subjects were studied of and O'Brien, 1966; Burch et al., 1966; O'Brien et al., whom 30 were female (mean age 27 6 years ± SEM 1966; Prior and Rose, 1966), although different 1 * 87, range 18 to 52 years) and 27 were male (mean measures of body bulk have yielded varying age 29 - 7 years + 1 * 90, range 21 to 57 years). Each subject was receiving a normal solid and fluid diet and none had taken alcohol within the 24 hours for November 1977 Accepted publication 20, the study. Height (cm) and weight (kg) preceding Dr A. to C. for Centre Correspondence RheuKennedy, were measured and a sample of serum was separated matic Diseases, 35 Baird Street, Glasgow G4 OEH. 333 -
334 Kennedy, Boddy, King, Brennan, Anderson, Buchanan
for uric acid estimation (standard colorimetric serum uric acid and analyse that regression, then to autoanalyser technique employing phosphotungstic add the second variable that is most highly coracid). related after adjustment for the first variable and give In 14 normal males and 11 females (mean age the analysis, and then to add the third next highly 32 2 years ± SEM 2 1, range 18 to 57) a further correlated variable, and so on. The rationale of the sample of venous blood was obtained for the deter- Principal Component Analysis is to construct a new mination of plasma urea and potassium concen- set of variables which are linearly related to the tration, red cell potassium (Boyd, 1970), and packed original variables, in this study being 11 in number, cell volume. such that the first few variables should contain as Total body potassium was measured in each much 'information' as possible. For example, in this subject using the Merlin mobile shadow-shield study the first principal component accounted for whole-body monitor (Boddy, 1967). The subject 67 % of the total variance, but when taken with the counting rate in the potassium-40 photopeak second principal component accounted for 79 % of (1 * 36-1 56 MeV) was expressed as mmol of potas- the total variance, etcetera. sium without the administration of a radioactive isotope, using the procedure described in detail Results elsewhere (Boddy et al., 1971). The estimated coefficient of variation of this procedure was shown to The mean, SEM, and range of each parameter be ± 3.9 % for a subject having 3600 mmol measured in the normal subjects is shown in Table 1 potassium. and each is in accord with values obtained in our By employing the formulae and tables of Hume own and in other Caucasian studies. and Goldberg (1964), it was possible to obtain an The results of the regression analysis of serum estimate of total blood volume, total red blood cell uric acid concentration on height, weight, sex, lean volume, and total plasma volume. Subsequently body mass (measured and predicted), and total body from these figures an estimate of total plasma uric potassium (measured and predicted) in 57 subjects acid could be obtained for all the control subjects and on the plasma urea, plasma potassium, and and total plasma potassium and total red cell intra-red blood cell potassium concentrations in potassium in the 14 male and 11 female subjects 25 subjects on whom it was possible to obtain these where plasma and red blood cell potassium results measurements are shown in Table 2. It can be seen were available. that a significant regression exists for serum uric acid on height, weight, sex, lean body mass and STATISTICAL METHODS total body potassium (both measured and preA step-wise regression and Principal Component dicted) but not for serum uric acid on plasma urea, Analysis was carried out using two BMD packages potassium, and intra red blood cell potassium on the Oxford 1906 computer of the serum uric acid concentrations. concentration on sex, total body potassium, and The step-wise regression and principal component serum urea. Linear regressions of total serum uric analysis results indicated that sex was the variable acid on total body potassium, of total red cell most highly correlated with the serum uric acid potassium and total serum potassium on total body concentration and when adjustment was made for potassium were calculated by the method of least this all other factors did not show a significant squares. The rationale of the step-wise regression is correlation with the serum uric acid concentration. to take the variable most highly correlated with Fig. 1 illustrates the plot of measured total body Table 1 Clinical and laboratory data expressed as mean i SEM in 57 normal subjects Weight (kg)
Measured
(cm)
TBK(gm)
LBMfrom TBK(kg)
173 i 1.4
69-8 i 2.4
146.1
56.3 i
159-4
59 3 +
96.7 +
1.7
2-1
Height
Males
Females
i 1.0
3-4
0-67 43.4 + 0-5
Uric acid
Plasma K
Red blood cellK
Plasma urea
Packed cell
(mg/l00 ml)
(mmol/l)
(mmol/l)
(mg/l0O ml)
volume
6-2
3-95
45
43.6
0.16
32.5 + i
0-15
4-3 i 0.14
3.86 ± 0.1
+ 0.68 42-2 t 1.1
1.7 29-4
+ 2-9
(Y.)
0.39 40.3
± 0.57
TBK = total body potassium. LBM = lean body mass. Conversion: traditional to SI units-Uric acid: 1 mg/100 ml sO- 595 mmol/l. Plasma potassium and red blood cell potassium: 1 mEq/l= 1 mmol/l. Plasma urea: 1 mg/100 mlsO- 166 mmol/l. Packed cell volume: 1 vol %=0-01.
The relationship between uric acid and potassium in normal subjects 335 Table 2 The separate regressions of serum uric acid concentration on the independent variables measured in the population studied, where P is the regression (3)
Independent variable
Slope
Height (cm) Weight (kg) Sex Lean body mass (LBM) Total body potassium (TBK) Height, weight, age, TBK (predicted) Height, age, TBK (predicted) Height, weight, LBM* Plasma urea concentration Plasma potassium concentration Intra-red blood cell potassium (male) Intra-red blood cell potassium (female)
0*064 0-047 1 *898 0-113 0-027 0*029 0-028 0-095 0-087 0-372 0-068 0*002
SE (f)
df
t
P
0-016 0-013 0.222 0-018 0-005 0-005 0-005 0-016 0-021 0*446 0-095 0-061
57 57 57 57 57 57 57 57 25 25 14 11
3 -93 3-77 8-50 6-34 5.93 5-78 5-22 6-06 0-97
0- I
280
Fig. 1 The correlation between total plasma uric acid and total body potassium in 30 female (*) and 27 male (o) subjects studied. r 0-84; P < 0 -001. =
potassium against total plasma uric acid and it can be seen that for the group as a whole there is a significant correlation (r = 0 84, P < 0 001) and when the group is broken down for sex the correlation persists for males (r = 0 64, P < 001), and for the female group (r = 0 45, P< 001). These results contrast with the lack of correlation between serum uric acid and plasma potassium concentration (mmol/l) and also intra-red blood cell potassium concentration (Table 3) in the total group or when these are split into male and female groups. It is of interest that there is a significant correlation between serum uric acid and height and weight when males and females are considered as a single group but when divided by sex, this significance disappears confirming the trend noted in the step-wise regression and principal component analysis. When serum uric acid concentration was expressed as g-1 total body potassium, the mean
value in males (0-043±0-001 SEM) was not significantly different (P
The relationship between uric acid and potassium in normal subjects ALASTAIR C. KENNEDY, KEITH BODDY, PRISCILLA C. KING, JENNIFER BRENNAN, JOHN A. ANDERSON, AND W. WATSON BUCHANAN From the Centre for Rheumatic Diseases, University Department of Medicine, Royal Infirmary, Glasgow; Scottish Universities Research and Reactor Centre, East Kilbride; and Department of Biomathematics, University of Oxford, Oxford, England SUMMARY The serum uric acid concentration in normal healthy subjects has been studied in relation to sex, height, weight, lean body mass measured from total body potassium and predicted from the Hume-Weyers formula (1971), total body potassium, plasma potassium and urea, and packed cell volume. The strongest correlation was found with sex, but height, weight, total body potassium, lean body mass (measured and predicted) also correlated significantly with serum uric acid concentration. However, when the sex variable was removed, the other factors lost their significant correlation. Finally, total red blood cell and plasma volumes were predicted (Hume and Goldberg, 1964) and from these an estimate of total plasma uric acid, total plasma potassium, and total red blood cell potassium obtained. Measured total body potassium was found to correlate well with total plasma potassium and total red blood cell potassium independent of sex. Total plasma uric acid correlated well with measured total body potassium when both sexes were considered and when separated into male and female groups the males retained a significant correlation as did the female group.
Serum uric acid concentrations, although subject in relationships to serum uric acid concentration (Evans the individual to marked fluctuation, are distributed et al., 1968). Evans et al. (1968) found that ponderal unimodally in large scale population studies index bore a slightly better relationship to serum (Mikkelsen et al., 1965) and it would seem from uric acid than did body weight, but the relative twin studies that the major determinant of serum importance of body fat or lean body mass in uric acid levels are environmental rather than determining serum uric acid has never been fully genetic (Boyle et al., 1967). Several contributing explored. factors, in addition to dietary intake, have been In the present report, serum uric acid has been studied; haemoglobin concentration and alcohol studied in relation to lean body mass, as represented consumption (Evans et al., 1968) and psychological by direct measurements of total body potassium, traits (Brooks and Mueller, 1966; Kasl et al., 1966) similarly the relationship of total body potassium to have all been reported to be related to the serum parameters of blood potassium have been inuric acid concentration. vestigated. That serum uric acid and body bulk are interrelated has been documented in several races with a Materials and methods variety of geographic, ethnic, and demographic characteristics (Dunn et al., 1963; Prior et al., 1964; SUBJECTS Mikkelsen, 1965; Mikkelsen et al., 1965; Acheson Fifty-seven normal healthy subjects were studied of and O'Brien, 1966; Burch et al., 1966; O'Brien et al., whom 30 were female (mean age 27 6 years ± SEM 1966; Prior and Rose, 1966), although different 1 * 87, range 18 to 52 years) and 27 were male (mean measures of body bulk have yielded varying age 29 - 7 years + 1 * 90, range 21 to 57 years). Each subject was receiving a normal solid and fluid diet and none had taken alcohol within the 24 hours for November 1977 Accepted publication 20, the study. Height (cm) and weight (kg) preceding Dr A. to C. for Centre Correspondence RheuKennedy, were measured and a sample of serum was separated matic Diseases, 35 Baird Street, Glasgow G4 OEH. 333 -
334 Kennedy, Boddy, King, Brennan, Anderson, Buchanan
for uric acid estimation (standard colorimetric serum uric acid and analyse that regression, then to autoanalyser technique employing phosphotungstic add the second variable that is most highly coracid). related after adjustment for the first variable and give In 14 normal males and 11 females (mean age the analysis, and then to add the third next highly 32 2 years ± SEM 2 1, range 18 to 57) a further correlated variable, and so on. The rationale of the sample of venous blood was obtained for the deter- Principal Component Analysis is to construct a new mination of plasma urea and potassium concen- set of variables which are linearly related to the tration, red cell potassium (Boyd, 1970), and packed original variables, in this study being 11 in number, cell volume. such that the first few variables should contain as Total body potassium was measured in each much 'information' as possible. For example, in this subject using the Merlin mobile shadow-shield study the first principal component accounted for whole-body monitor (Boddy, 1967). The subject 67 % of the total variance, but when taken with the counting rate in the potassium-40 photopeak second principal component accounted for 79 % of (1 * 36-1 56 MeV) was expressed as mmol of potas- the total variance, etcetera. sium without the administration of a radioactive isotope, using the procedure described in detail Results elsewhere (Boddy et al., 1971). The estimated coefficient of variation of this procedure was shown to The mean, SEM, and range of each parameter be ± 3.9 % for a subject having 3600 mmol measured in the normal subjects is shown in Table 1 potassium. and each is in accord with values obtained in our By employing the formulae and tables of Hume own and in other Caucasian studies. and Goldberg (1964), it was possible to obtain an The results of the regression analysis of serum estimate of total blood volume, total red blood cell uric acid concentration on height, weight, sex, lean volume, and total plasma volume. Subsequently body mass (measured and predicted), and total body from these figures an estimate of total plasma uric potassium (measured and predicted) in 57 subjects acid could be obtained for all the control subjects and on the plasma urea, plasma potassium, and and total plasma potassium and total red cell intra-red blood cell potassium concentrations in potassium in the 14 male and 11 female subjects 25 subjects on whom it was possible to obtain these where plasma and red blood cell potassium results measurements are shown in Table 2. It can be seen were available. that a significant regression exists for serum uric acid on height, weight, sex, lean body mass and STATISTICAL METHODS total body potassium (both measured and preA step-wise regression and Principal Component dicted) but not for serum uric acid on plasma urea, Analysis was carried out using two BMD packages potassium, and intra red blood cell potassium on the Oxford 1906 computer of the serum uric acid concentrations. concentration on sex, total body potassium, and The step-wise regression and principal component serum urea. Linear regressions of total serum uric analysis results indicated that sex was the variable acid on total body potassium, of total red cell most highly correlated with the serum uric acid potassium and total serum potassium on total body concentration and when adjustment was made for potassium were calculated by the method of least this all other factors did not show a significant squares. The rationale of the step-wise regression is correlation with the serum uric acid concentration. to take the variable most highly correlated with Fig. 1 illustrates the plot of measured total body Table 1 Clinical and laboratory data expressed as mean i SEM in 57 normal subjects Weight (kg)
Measured
(cm)
TBK(gm)
LBMfrom TBK(kg)
173 i 1.4
69-8 i 2.4
146.1
56.3 i
159-4
59 3 +
96.7 +
1.7
2-1
Height
Males
Females
i 1.0
3-4
0-67 43.4 + 0-5
Uric acid
Plasma K
Red blood cellK
Plasma urea
Packed cell
(mg/l00 ml)
(mmol/l)
(mmol/l)
(mg/l0O ml)
volume
6-2
3-95
45
43.6
0.16
32.5 + i
0-15
4-3 i 0.14
3.86 ± 0.1
+ 0.68 42-2 t 1.1
1.7 29-4
+ 2-9
(Y.)
0.39 40.3
± 0.57
TBK = total body potassium. LBM = lean body mass. Conversion: traditional to SI units-Uric acid: 1 mg/100 ml sO- 595 mmol/l. Plasma potassium and red blood cell potassium: 1 mEq/l= 1 mmol/l. Plasma urea: 1 mg/100 mlsO- 166 mmol/l. Packed cell volume: 1 vol %=0-01.
The relationship between uric acid and potassium in normal subjects 335 Table 2 The separate regressions of serum uric acid concentration on the independent variables measured in the population studied, where P is the regression (3)
Independent variable
Slope
Height (cm) Weight (kg) Sex Lean body mass (LBM) Total body potassium (TBK) Height, weight, age, TBK (predicted) Height, age, TBK (predicted) Height, weight, LBM* Plasma urea concentration Plasma potassium concentration Intra-red blood cell potassium (male) Intra-red blood cell potassium (female)
0*064 0-047 1 *898 0-113 0-027 0*029 0-028 0-095 0-087 0-372 0-068 0*002
SE (f)
df
t
P
0-016 0-013 0.222 0-018 0-005 0-005 0-005 0-016 0-021 0*446 0-095 0-061
57 57 57 57 57 57 57 57 25 25 14 11
3 -93 3-77 8-50 6-34 5.93 5-78 5-22 6-06 0-97
0- I
280
Fig. 1 The correlation between total plasma uric acid and total body potassium in 30 female (*) and 27 male (o) subjects studied. r 0-84; P < 0 -001. =
potassium against total plasma uric acid and it can be seen that for the group as a whole there is a significant correlation (r = 0 84, P < 0 001) and when the group is broken down for sex the correlation persists for males (r = 0 64, P < 001), and for the female group (r = 0 45, P< 001). These results contrast with the lack of correlation between serum uric acid and plasma potassium concentration (mmol/l) and also intra-red blood cell potassium concentration (Table 3) in the total group or when these are split into male and female groups. It is of interest that there is a significant correlation between serum uric acid and height and weight when males and females are considered as a single group but when divided by sex, this significance disappears confirming the trend noted in the step-wise regression and principal component analysis. When serum uric acid concentration was expressed as g-1 total body potassium, the mean
value in males (0-043±0-001 SEM) was not significantly different (P
