Decreasing serum uric acid levels might be associated with improving estimated glomerular filtration rate (eGFR) in Japanese men

doi:10.4236/health.2011.38082

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Vol.3, No.8, 498-503 (2011)

doi:10.4236/health.2011.38082

Health

Decreasing serum uric acid levels might be associated

with improving estimated glomerular filtration rate

(eGFR) in Japanese men

No buyuki Miyatake1*, Kenichi Shikata2,3, Hirofumi Makino3, Takeyuki Numata4

1Department of Hygiene, Faculty of Medicine, Kagawa University, Kagawa, Japan;

*Corresponding Autor: [email protected]

2Center for Innovative Medicine, Okayama University Hospital, Okayama, Japan;

3Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical

Sciences, Okayama, Japan;

4Okayama Southern Institute of Health, Okayama Health Foundation, Okayama, Japan.

Received 8 June 2011; revised 20 July; accepted 31 July 2011.

ABSTRACT

The link between changes in a subject’s serum

uric acid levels and his estimated glomerular

filtration rate (eGFR) was evaluated in Japanese

men. We used data for 108 Japanese men (45.3

± 8.0 years) with a 1-year follow up. eGFR was

defined by a new equation developed for Japan.

eGFR was weakly correlated with serum uric

acid levels (r = –0.287, p = 0.0026) at baseline.

Subjects were given advice for dietary and life-

style improvement. At the 1-year follow up, al-

most metabolic syndrome components were

significantly improved. However, blood sugar

and uric acid did not change and eGFR was

significantly decreased. The changes in eGFR

were weakly correlated with abdominal circum-

ference (r = –0.249, p = 0.0094) and uric acid (r =

–0.340, p = 0.0003). A decrease in serum uric

acid levels may be associated with improving

eGFR in Japanese men.

Keywords: Abdominal Circumference; Uric Acid;

Estimated Glomerular Filtration Rate (eGFR);

Metabolic Syndrome; Lifestyle Modification

1. INTRODUCTION

Chronic kidney disease (CKD) has become a public

health challenge and is a common disorder [1]. For ex-

ample, about 20% of adults have CKD, which is defined

as kidney damage or a glomerular filtration rate (GFR)

<60 ml/min/1.73 m2 for at least three months regardless

of cause [2]. We have also previously reported in a

cross-sectional study that the estimated glomerular fil-

tration rate (eGFR) [3] in men with abdominal obesity

and in women with hypertension was significantly lower

than that in subjects without these components of meta-

bolic syndrome [4]. In addition, we also showed that

decreasing abdominal circumference in men and de-

creasing systolic blood pressure in women were associ-

ated with improving eGFR with lifestyle modification [5,

6]. In turn, there some reports according to the link be-

tween serum uric acid levels and CKD in foreign coun-

tries [7-12]. However, whether decreases in serum uric

acid levels are beneficial for improving eGFR, and what

affects this has on eGFR remain to be investigated in a

longitudinal study in Japanese men.

In this study, we evaluate the link between changes in

eGFR and changes in serum uric acid levels in Japanese

men with a 1-year follow up.

2. SUBJECTS AND METHODS

2.1. Subjects

We used data for 108 Japanese men, aged 45.3 ± 8.0

years, who met the following criteria: 1) received a

health check-up including special health guidance and a

follow-up check-up 1-year later, 2) received anthropo-

metric measurements, fasting blood examination includ-

ing serum uric acid levels and blood pressure measure-

ments as part of the annual health check-up, 3) received

no medications for diabetes, hypertension, and/or dysli-

pidemia, and 4) provided written informed consent (Ta-

ble 1).

At the first health check-up, all subjects were given

instructions by well-trained medical staff on how to

change their lifestyle as special health guidance. Nutri-

tional instruction was provided with a well-trained nutri-

tionist, who planned a diet for each subject based on

their data and provided simple instructions (i.e. not to eat

N. Miyatake et al. / Health 3 (2011) 498-503

499

Table 1. Clinical characteristics and changes in parameters with 1-year follow up.

Baseline Follow up p

Number of Subjects 108

Age 45.3 ± 8.0

Height (cm) 168.9 ± 5.3

Body weight (kg) 76.5 ± 11.5 74.9 ± 10.8 <0.0001

Body mass index (kg/m2) 26.8 ± 3.5 26.2 ± 3.3 0.0001

Abdominal circumference (cm) 89.1 ± 9.9 86.9 ± 9.3 <0.0001

Systolic blood pressure (mmHg) 131.4 ± 14.5 123.6 ± 12.1 <0.0001

Diastolic blood pressure (mmHg) 82.4 ± 11.4 77.0 ± 8.9 <0.0001

Triglyceride (mg/dl) 158.1 ± 114.4 126.4 ± 83.0 0.0029

HDL cholesterol (mg/dl) 53.3 ± 14.5 55.6 ± 14.7 0.0260

Blood sugar (mg/dl) 103.4 ± 18.4 104.7 ± 29.6 0.4731

Uric acid (mg/dl) 6.1 ± 1.3 6.0 ± 1.3 0.3862

Cr (mg/dl) 0.80 ± 0.11 0.83 ± 13.3 0.0002

eGFR (ml/min/1.73 m2) 85.0 ± 14.0 806. ± 13.3 <0.0001

Mean ± SD

too much and to consider balance when they eat). Exer-

cise instruction was also provided by a well-trained

physical therapist, who encouraged each subject to in-

crease their daily amount of steps walked.

Ethical approval for the study was obtained from the

Ethical Committee of Okayama Health Foundation.

2.2. Anthropometric and Body Composition

Measurements

Anthropometric and body compositions were evalu-

ated based on the following parameters: height, body

weight and abdominal circumference. Body mass index

(BMI) was calculated by weight/[height]2, in kg/m2.

Abdominal circumference was measured at the umbilical

level in standing subjects after normal expiration [13].

2.3. Blood Pressure Measurements at Rest

Resting systolic and diastolic blood pressures were

measured indirectly using a mercury sphygmomanome-

ter placed on the right arm of the seated participant after

at least 15 min of rest.

2.4. Urine Examination

Urine samples were collected from the second- morn-

ing urine (before 10 a.m.) and subjected to examination

within 1 h. The urine examination was performed using

urine test strips (BAYER, Tokyo, Japan). The reagent

strip was dipped directly into the urine sample. Just after

dipping, the sample was graded as –: negative, ±: trace

positive, +: positive (30 mg/dl), 2+: positive (100 mg/dl),

3+: positive (300 mg/dl) or 4+: positive (1,000 mg/dl) by

comparison with a standard color chart found on the

container’s label.

2.5. Blood Sampling and Assays

We measured overnight fasting serum levels of create-

nine (Cr) (enzymatic method), uric acid, high-density

lipoprotein (HDL) cholesterol, triglycerides (L Type

Wako Triglyceride・H, Wako Chemical, Osaka, Japan)

and blood sugar. eGFR was calculated using the follow-

ing equation: eGFR (ml/min/1.73 m2) = 194 × Cr–1.094 ×

Age–0.287 [3]. Reduced eGFR was defined as an eGFR <

60 ml/min/1.73 m2. Serum uric acid levels were meas-

ured by the Uricase-Peroxidase method. The institutional

normal range was 2.5 - 7.0 mg/dl.

2.6. Definition of Metabolic Syndrome

Men with an abdominal circumference in excess of 85

cm were defined as having metabolic syndrome if they

also had two or more of the following components: 1)

Dyslipidemia: triglycerides ≥ 150 mg/dl and/or HDL

cholesterol < 40 mg/dl, 2) High blood pressure: blood

pressure ≥ 130/85 mmHg, 3) Impaired glucose tolerance:

fasting plasma glucose ≥ 110 mg/dl [13].

2.7. Statistical Analysis

Data are expressed as means ± standard deviation

(SD). A statistical analysis was performed using a paired

t test, χ2 test and covariance analysis: p < 0.05 was con-

sidered to be statistically significant. Pearson，s correla-

N. Miyatake et al. / Health 3 (2011) 498-503

500

tion coefficients were calculated and used to test the

significance of the linear relationship among continuous

variables; stepwise multiple regression analysis was also

used.

3. RESULTS

The clinical parameters at the baseline and the 1-year

follow up are summarized in Tab le 1 . Anthropometric,

body composition parameters and metabolic syndrome

components, except blood sugar, were significantly im-

proved with lifestyle modification after one year. How-

ever, serum uric acid levels did not change, and Cr was

significantly increased and eGFR was significantly de-

creased. However, thirty five subjects was diagnosed as

having metabolic syndrome at baseline and seventeen

subjects was diagnosed as having metabolic syndrome,

and subjects with metabolic syndrome were significantly

reduced after one year (p < 0.0001). One subject was

diagnosed with reduced eGFR at baseline and two sub-

jects were diagnosed with reduced eGFR at the 1-year

follow up. In addition, four subjects were identified as

trace positive, two subjects were identified as positive (+)

and one subject was identified as positive (2+) for pro-

teinuria at baseline and five subjects were identified as

trace positive, four subjects were identified as positive

(+) and two subjects were identified as positive (2+) at

the 1-year follow up.

In subjects not taking medications, we also compared

eGFR levels between the groups with and without each

component of the Japanese definition of metabolic syn-

drome (Tabl e 2). To avoid the influence of age, we used

age as a covariate and compared eGFR between men

with and those without metabolic syndrome components

using covariance analysis. There were no significant di-

fferences in eGFR between the groups with or without

components of metabolic syndrome. In addition, eGFR

in subjects with metabolic syndrome was similar to that

in subjects without it, even after adjusting for age. Se-

rum uric acid levels was negatively and weakly corre-

lated with eGFR at baseline (r = –0.287, p = 0.0026)

(Figure 1).

We further evaluated the relationship between changes

in eGFR and changes in clinical parameters. Changes in

eGFR were weakly correlated with changes in abdomi-

nal circumference (r = –0.249, p = 0.0094) (Table 3).

However, changes in eGFR were not significantly corre-

lated with changes in other metabolic components. Changes

in eGFR were negatively correlated with changes in se-

rum uric acid levels (r = –0.340, p = 0.0003) (Ta b l e 3 ,

Figure 2). We also used stepwise multiple regression

analysis to evaluate the effect of changes in clinical pa-

rameters, i.e. age, abdominal circumference, systolic

blood pressure, diastolic blood pressure, triglyceride,

HDL cholesterol, blood sugar and serum uric acid levels

on the change in eGFR, and found that only change in

abdominal circumference and serum uric acid levels

were significant [Change in eGFR = –5.296 – 0.330

(change in abdominal circumference) –3.259 (change in

uric acid) , r2 = 0.149, p = 0.0002].

4. DISCUSSION

Iseki et al. [14], Ninomiya T et al. [15] and Tanaka et

al. [16] showed that metabolic syndrome, using the mo-

dified ATP III definition [17], was associated with CKD

in the Japanese population. Compared with subjects with

0 or 1 component of metabolic syndrome, subjects with

2, 3 and 4 or more components had odds ratios of 1.13,

1.90 and 2.79 for CKD [15]. In this study, thirty five

Table 2. Comparison of eGFR between men with and without metabolic syndrome.

Abdominal obesity (–) Abdominal obesity (+) p p (Afrer adjusting for age)

Number of subjects 35 73

eGFR (ml/min/1.73 m2) 80.3 ± 14.5 87.2 ± 13.3 0.01680.6214

Impaired glucose torelance (–)Impaired glucose torelance (+)

Number of subjects 84 24

eGFR (ml/min/1.73 m2) 83.9 ± 13.9 88.8 ± 13.8 0.12460.8832

Hypertension (–) Hypertension (+)

Number of subjects 43 65

eGFR (ml/min/1.73 m2) 83.8 ± 15.5 85.8 ± 13.0 0.46880.8588

Dyslipidemia (–) Dyslipidemia (+)

Number of subjects 60 48

eGFR (ml/min/1.73 m2) 84.0 ± 14.3 86.2 ± 13.6 0.40520.7367

Metabolic syndrome (–) Metabolic syndrome (+)

Number of subjects 73 35

eGFR (ml/min/1.73 m2) 83.7 ± 14.2 87.6 ± 13.4 0.18520.3008

Mean ± SD

N. Miyatake et al. / Health 3 (2011) 498-503

501

Table 3. Simple correlation analysis between changes in eGFR and changes in clinical parameters

with 1-year follow up.

r p

Abdominal circumference (cm) –0.249 0.0094

Systolic blood pressre (mmHg) –0.101 0.2996

Diastolic blood pressure (mmHg) 0.025 0.7946

Triglyceride (mg/dl) –0.050 0.6071

HDL cholesterol (mg/dl) –0.044 0.6496

Blood sugar (mg/dl) –0.037 0.7011

Uric acid (mg/dl) –0.340 0.0003

ml/min/ 1 .73 m2

eGFRin men

Serum uric acid levelmg/dl

n = 108

r = –0.287

p = 0.0026

100

110

120

130

140

0123 4 5 6 7 8910 11

Figure 1. Simple correlation analysis between eGFR and serum uric acid levels at baseline.

–40

–30

–10

–4 –3 –2 –10 1 2 3

Changes in serum uric acid level

ml/min /1.73m2

Changes in eGFRin men

mg/dl

n = 108

r = –0.340

p = 0.0003

Figure 2. Simple correlation analysis between changes in eGFR and changes in serum uric

acid levels at 1-year follow up.

N. Miyatake et al. / Health 3 (2011) 498-503

502

subjects was diagnosed as having metabolic syndrome,

using the Japanese criteria, at baseline and seventeen

subjects were diagnosed as having metabolic syndrome

at the 1-year follow up. We have previously reported that

the prevalence of metabolic syndrome was 30.7% in

Japanese men [18]. In this study, with lifestyle modifica-

tion after the initial health check-up, metabolic compo-

nents were significantly improved in men without medi-

cations at the one year follow-up. Although eGFR and

serum uric acid levels were not improved after one year,

changes in eGFR were negatively correlated with changes

in serum uric acid levels. Taken together, reducing serum

uric acid levels such as medications may be useful for

improving eGFR in Japanese men.

Openly accessible at

Higher serum uric acid levels contribute to the devel-

opment of renal injury and end-stage renal disease [7-12].

Satirapoj B et al. reported in a cross-sectional study that

high serum uric acid level was independently associated

with increased prevalence of CKD in 5546 Southeast

Asian population [7]. The age-adjusted odds ration for

CKD, with subjects with no hyperuricemia and no meta-

bolic syndrome, was 5.85 for subjects with both hyperu-

ricemia and metabolic syndrome [8]. Yen CJ et al. also

showed that serum uric acid levels were associated with

eGFR and decline in renal function in elderly Taiwanese

subjects by longitudinal analysis [9]. In Japanese, hype-

ruricemia, hypercholesterolemia and diabetes are risk

factors for CKD in peripheral arterial disease [19]. In the

present study, there was weak relationship between

eGFR and serum uric acid levels at baseline. In addition,

we revealed that, changes in serum uric acid levels were

correlated with changes in eGFR in men without medi-

cations. Changes in other metabolic components, except

abdominal circumference, were not linked to changes in

eGFR. Therefore, the clinical impact of serum uric acid

levels on eGFR was noted in Japanese men.

Potential limitations remain in our study. First, the

small sample size in our study makes it difficult to infer

causality between eGFR and serum uric acid levels. In

addition, eGFR and serum uric acid levels were not in-

creased with lifestyle modification after one year. Sec-

ond, we also could not reveal the mechanism of the lin-

kage between eGFR and serum uric acid levels. Third,

most of the enrolled subjects were not diagnosed as

CKD at baseline. Therefore, the results in this study may

not apply for patients with CKD. Further prospective

studies using medications are needed in Japanese sub-

jects.

5. ACKNOWLEDGEMENTS

This research was supported in part by Health and Labor Sciences

Research Grants from the Ministry of Health, Labor and Welfare,

Japan.

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