Vol.3, No.6, 394-399 (2011)
doi:10.4236/health.2011.36066
C
opyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
Health
Comparison of ventilatory threshold between subjects
with and without proteinuria in Japanese
Nobuyuki Miyatake1*, Kenichi Shikata2,3, Hirofumi Makino3, Takeyuki Numata4
1Department of Hygiene, Faculty of Medicine, Kagawa University, Kagawa, Japan; *Corresponding Author:
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 20 April 2011; revised 30 May 2011; accepted 1 June 2011.
ABSTRACT
We compared the levels of ventilatory threshold
(VT) between subjects with and without pro-
teinuria. We used data of 402 men and 413
women who were not taking any medications,
aged 20 - 77 years, in this cross-sectional in-
vestigation study. Aerobic parameters at VT i.e.
oxygen uptake, work rate and heart rate, and
exercise habits were evaluated, which are con-
sidered to be cardio respiratory fitness. Pro-
teinuria was measured by using urine strip de-
vices. Forty three men (10.7%) and 29 women
(7.0%) were diagnosed as having the proteinuria
(± ≦). There were no significant relationships
between proteinuria and exercise habits in both
sexes after adjusting for age. Oxygen uptake at
VT in subjects w ith proteinuria was significantly
lower than that in subjects without proteinuria
after adjusting for age in men. However, such
link was not noted in women after adjusting for
age (p = 0.9964). Finally, associations were at-
tenuated after adjusting for age and exercise
habits in both sexes. Among Japanese not tak-
ing medications, proteinuria might be a modifi-
able factor of VT, especially in Japanese men.
Keywords: Proteinruia; Ventilatory Threshold (VT);
Exercise Ha bits
1. INTRODUCTION
Chronic kidney disease (CKD) has become an impor-
tant public health challenge in Japan and it is a major
risk factor for the end stage renal disease, cardiovascular
disease and premature death [1,2]. For example, 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 [3].
We have also previously reported in a cross-sectional
study that the estimated glomerular filtration rate (eGFR)
[4] in men with abdominal obesity and in women with
hypertension was significantly lower than that in sub-
jects without these components of metabolic syndrome
[5]. In addition, we have also showed that proteinuria
was closely linked to lower eGFR and it might be useful
marker for CKD in Japanese [6].
The ventilatory threshold (VT), which is one of pa-
rameters of the cardio respiratory fitness, is defined as
the upper limit of the aerobic exercise and is thought to
serve as an accurate and reliable standard for exercise
prescription [7]. Since the exercise intensity at VT is not
harmful to cardiovascular function, it can be safely ap-
plied to patients with myocardial infarction as exercise
prescription [8]. However, the link between cardio res-
piratory fitness using VT and proteinuria remains to be
investigated.
In this study, we investigated cardio respiratory fitness
evaluated by VT in Japanese and evaluated the clinical
impact of proteinuria on VT in subjects not taking
medications.
2. METHODS
2.1. Subjects
We used all data on 815 Japanese (402 men and 413
women) aged 20 - 77 years in a cross-sectional study. All
subjects met the following criteria: 1) they had wanted to
change their lifestyle i.e. diet and exercise habits, and
had received an annual health checkup at Okayama
Southern Institute of Health; 2) they had received VT,
urine examination and anthropometric measurements as
part of their annual health checkups; 3) they had re-
ceived no medications for diabetes, hypertension, and/or

N. Miyatake et al. / Health 3 (2011) 394-399
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
395395
dyslipidemia; and 4) they provided informed consent
(Table 1).
The study was approved by the Ethics Committee of
Okayama Health Foundation.
2.2. Anthropometric Measurement s
The anthropometric parameters were evaluated by us-
ing the following respective parameters such as height,
body weight, body mass index (BMI), abdominal cir-
cumference, and hip circumference. BMI was calculated
by weight/[height]2 (kg/m2). The abdominal circumfer-
ence was measured at the umbilical level and the hip was
measured at the widest circumference over the tro-
chanter in standing subjects after normal expiration [9].
2.3. Exercise Testing
A graded ergometer exercise protocol [10] was per-
formed. Two hours after breakfast, a resting ECG was
recorded and blood pressure was measured. Then, all
participants were given graded exercise after 3 min of
pedaling on an unloaded bicycle ergometer (Excalibur
V2.0, Lode BV, Groningen, Netherlands). The profile of
incremental workloads was automatically defined by the
methods of Jones [10], in which the workloads reach the
predicted VO2 max in 10 min. A pedaling cycle of 60
rpm was maintained. Loading was terminated when the
appearance of symptoms forced the subject to stop.
During the test, ECG was monitored continuously to-
gether with the recording of heart rate (HR). Expired gas
was collected and rates of oxygen consumption (VO2)
and carbon dioxide production (VCO2) were measured
breath-by-breath using a cardiopulmonary gas exchange
system (Oxycon Alpha, Mijnhrdt b.v., Netherlands). VT
was determined by the standard of Wasserman et al [7],
Davis et al [11], and the V-slope method of Beaver [12]
from VO2, VCO2 and minute ventilation (VE). At VT,
VO2 (ml/kg/min), work rate (W), and heart rate (beats/
min) were measured and recorded.
2.4. Urine Examination
Urine samples were collected from the second-mor-
ning urine (before 10 a.m.) and examined within 1 hour.
The urine examination was performed using urine strip
tests (BAYER, Tokyo, Japan). The reagent strip was
dipped directly into the urine sample. Just after dipping,
the sample is graded as −: negative, ±: trace positive, +:
positive (30 mg/dl), 2+: positive (100 mg/dl), 3+: posi-
tive (300 mg/dl) or 4+: positive (1000 mg/dl) by com-
parison with a standard color chart found on the con-
tainer’s label [13].
2.5. Exercise Habits
The data on exercise habits was obtained at interviews
by well-trained staff in a structured way. The subjects
were asked if they currently exercise (over the level of
30 minutes per time, two times per week and prolong
duration for 3 months). When the answer was “yes”,
they were classified as subjects with exercise habits.
When the answer was “no”, they were classified as sub-
jects without exercise habits.
Table 1. Clinical profiles of enrolled subjects.
Men Women
Men ± SD MinimumMaximumMen ± SD Minimum Maximum
Number of subjects 402 413
Age 42.3 ± 11.5 20 77 45.1 ± 12.1 20 71
Height (cm) 169.7 ± 5.9 152.2 187.2 156.1 ± 5.5 141.7 176.1
Weight (kg) 78.8 ± 13.1 45.3 121.9 64.9 ± 12.0 39.9 116.9
Body mass index (kg/m2) 27.3 ± 4.1 16.8 41.5 26.6 ± 4.8 15.4 48.7
Abdominal circumference (cm) 90.9 ± 10.8 62.5 130.0 81.5 ± 11.3 56.0 123.6
Hip circumference (cm) 98.5 ± 6.8 79.8 120.0 96.6 ± 8.5 72.5 132.0
Heart rate at rest (beat/min) 73.6 ± 12.4 43.0 117.0 73.2 ± 11.9 6.0 135.0
Systolic blood pressure (mm Hg) 137.3 ± 16.7102.0 191.0 135.0 ± 20.9 82.0 188.0
Diastolic blood pressure (mm Hg) 86.1 ± 12.2 54.0 131.0 83.0 ± 12.8 50.0 122.0
Oxygen uptake at ventilatory threshold (ml/kg/min) 14.9 ± 3.9 8.7 33.9 12.6 ± 2.5 7.8 27.3
Work rate at ventilatory threshold (watt) 82.8 ± 24.5 35.0 190.0 51.2 ± 14.8 15.0 125.0
Heart rate at ventilatory threshold (beat/min) 105.9 ± 11.970.0 149.0 106.8 ± 11.7 71.0 147.0

N. Miyatake et al. / Health 3 (2011) 394-399
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396
2.6. Statistical Analysis
All data are expressed as mean ± standard deviation
(SD) values. A statistical analysis was performed using
an unpaired t test, χ2 test, logistic regression analysis and
covariance analysis, where p < 0.05 was considered to
be statistically significant. We used the unpaired t test to
compare parameters between subjects with and without
proteinuria; the χ2 test was used to evaluate the relation-
ship between prevalence of proteinuria and exercise hab-
its. Logistic regression analysis and covariance analysis
were also used to adjust for parameters. ANOVA and
Scheffe’s F test were also used to compare among sub-
jects with and without proteinuria and exercise habits.
3. RESULTS
Clinical profiles are summarized in Ta b l e 1 . Oxygen
uptake at VT was 14.9 ± 3.9 ml/kg/min in men and 12.6
± 2.5 ml/kg/min in women. Prevalence of proteinuria in
enrolled subjects is also summarized in Tab l e 2. A total
of 43 men (10.7%) and 29 women (7.0%) was diagnosed
as having the proteinuria (± ≦).
We further evaluated the relationship between pro-
teinuria and exercise habits (Table 3). Significant rela-
tionships between proteinuria and exercise habits were
not noted in both sexes after adjusting for age.
We compared the parameters at VT between subjects
with and without proteinuria (Tab l e 4 ). In men, oxygen
uptake at VT in subjects with proteinuria was signifi-
cantly lower than that in subjects without proteinuria
even after adjusting for age by using covariance analysis
(p = 0.0114). It is well known that exercise habits are
closely associated with ventilatory threshold [14], and
significant difference of oxygen uptake at VT was at-
tenuated after adjusting for age and exercise habits (p =
0.4628). The significant differences of work rate and
heart rate at VT were not noted in men. In women, pa-
rameters at VT in subjects with proteinuria were not sig-
nificant different compared to those in subjects without
proteinuria.
We finally compared parameters at VT between sub-
jects with and without proteinuria and exercise habits [A:
proteinuria (−) exercise habits (+), B: proteinuria (−) ex-
ercise habits (−), C: proteinuria (+) exercise habits (+), D:
proteinuria (+) exercise habits (−)] (Table 5). In men,
oxygen uptake at VT in Group B and D was significantly
lower than that in Group A. Heart rate at VT in Group D
was significantly higher than that in Group A. In women,
oxygen uptake at VT in Group B was significantly lower
than that in Group A. Heart rate at VT in Group D was
significantly higher than that in Group A.
4. DISCUSSION
In this study, we firstly evaluated the link between
proteinuria and cardiorespilatory fitness using VT in
Japanese without any medications. Proteinuria might be
a modifiable factor of VT, especially in Japanese men.
It is well known that proteinuria and/or reduced renal
function were closely associated with cardio vascular
disease (CVD) [15,16]. Irie et al reported that they
evaluated 30,764 men and 60,668 women aged 40 - 79
years for 10 years, and proteinuria and hypercreatinemia
or reduced GFR and their combination were significant
predictors of CVD and all-cause mortality [15].
Anavekar et al also showed that even mild renal disease
Table 2. Prevalence of proteinuria in enrolled subject.
− ± 1+ 2+ 3+
% % % % %
Tot al
Men 359 89.3 21 5.2 14 3.5 5 1.2 3 0.7 402
Women 384 93.0 17 4.1 9 2.2 3 0.7 0 0.0 413
Table 3. Relationship between proteinuria and exercise habits.
Proteinuria (−) Proteinuria (± ≦) p p (After adjusting for age)
Men
Exercise habits (+) 152 12
Exercise habits (−) 207 31
0.0688 0.0921
Women
Exercise habits (+) 105 4
Exercise habits (−) 279 25
0.1104 0.1667

N. Miyatake et al. / Health 3 (2011) 394-399
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
397397
Table 4. Comparison of parameters at ventilatory threshold between subjects with and without proteinuria.
Proteinuria
(−)
Proteinuria
(± ≦)
Men ± SD Men ± SD
p P (After adjusting
for age)
p
(After adjusting
for age age and
exercise habits)
Men
Number of subjects 359 43
Age 42.7 ± 11.5 39.2 ± 11.5 0.0564
Oxygen uptake at ventilatory threshold (ml/kg/min) 15.1 ± 4.0 13.7 ± 2.8 0.0275 0.0114 0.4628
Work rate at ventilatory threshold (watt) 83.3 ± 25.3 78.7 ± 15.9 0.2440 0.3603 0.2947
Heart rate at ventilatory threshold (beat/min) 105.5 ± 12.0 109.1 ± 11.2 0.0591 0.4155 0.1050
Women
Number of subjects 384 29
Age 45.2 ± 12.2 42.6 ±11.0 0.2571
Oxygen uptake at ventilatory threshold (ml/kg/min) 12.6 ± 2.5 12.3 ± 1.7 0.5751 0.9964 0.2939
Work rate at ventilatory threshold (watt) 51.2 ± 15.1 51.4 ± 10.0 0.9477 0.3446 0.2382
Heart rate at ventilatory threshold (beat/min) 106.4 ± 11.6 112.2 ± 12.5 0.0102 0.4685 0.2028
Table 5. Comparison of parameters of ventilatory threshold between subjects with and without proteinuria and exercise habits.
Proteinuria (−) Proteinuria (−) Proteinuria (+) Proteinuria (+)
Exercise habits (+)Exercise habits (−)Exercise habits (+) Exercise habits (−)
Men
Number of subjects 152 207 12 31
Oxygen uptake at ventilatory threshold
(ml/kg/min) 16.7 ± 5.0 13.9 ±2.6 a14.8 ± 4.1 13.2 ± 2.0 a
Work rate at ventilatory threshold (watt) 90.9 ± 31.0 77.7 ± 18.4 a74.5 ± 16.3 80.3 ± 15.6
Heart rate at ventilatory threshold
(beat/min) 104.5 ± 13.1 106.1 ± 11.1 103.1 ± 12.4 111.4 ± 10.0 a
Women
Number of subjects 105 279 4 25
Oxygen uptake at ventilatory threshold
(ml/kg/min) 13.4 ± 3.4 12.3 ± 2.1 a10.6 ± 1.6 12.6 ± 1.6
Work rate at ventilatory threshold (watt) 54.3 ± 18.9 50.0 ± 13.2 41.2 ± 9.5 53.0 ± 9.2
Heart rate at ventilatory threshold
(beat/min) 104.1 ± 12.0 107.3 ± 11.3 101.8 ± 11.6 113.8 ± 12.0 a
a: p < 0.05 vs Proteinuria (−), Exercise habits (+)
was considered a major risk factor for CVD after myo-
cardial infarction in 14527 patients with acute myocar-
dial infarction [16]. However, according to the link be-
tween reduced renal function and cardiorespilatory fit-
ness, there were few studies especially in Japan. Okuno
et al reported that they evaluated 109 community-
dwelling frail elderly, aged 65 years and over, and they
found that functional reach and tandem stance were sig-
nificantly affected by eGFR [17]. Takhreen reviewed
that relationship between exercise intervention and qual-
ity of life (QOL) in CKD patients. Exercising patients
have shown improvements in physical fitness, psycho-
logical function, reaction times and lower extremity
muscle strength, and these factors help improve QOL
[18]. In this study, we solely evaluated the relationship
between proteinuria and aerobic exercise level defined
by VT in the Japanese without any medications. Exercise
habits were not significantly linked to proteinuria in both
sexes and the differences of parameters at VT between
subjects with and without proteinuria were attenuated

N. Miyatake et al. / Health 3 (2011) 394-399
Copyright © 2011 SciRes. Openly accessible at http://www.scirp.org/journal/HEALTH/
398
after adjusting for age and exercise habits in men. How-
ever, oxygen uptake at VT in women with proteinuria
was not significantly lower than that in women without.
In addition, we compared oxygen uptake at VT among
subjects with and without proteinuria and exercise habits,
and found that oxygen uptake at VT in Group D was the
lowest among 4 groups in men. Oxygen uptake at VT in
Group A was the highest among 4 groups in both sexes.
Taken together, promoting exercise habits might be con-
sidered for improving aerobic exercise level, and pro-
teinuria might be a modifiable factor of VT, especially in
Japanese men.
Potential limitations still remain in this study. First,
our study was a cross sectional and not a longitudinal
study. Second, 402 men and 413 women in our study
voluntarily underwent measurements: they were there-
fore more likely to be health-conscious compared with
the average person. Third, we could not show clear
mechanism between proteinuria and oxygen uptake at
VT. We have previously reported that brachial-ankle
pulse wave velocity (baPWV) in subjects with reduced
eGFR was significantly higher than that in subjects
without [19]. Arterial stiffness might affect the results. In
addition, low prevalence of proteinuria also affected the
results, especially in women. To show this, further pro-
spective studies are needed in the Japanese.
5. ACKNOWLEDGEMENTS
This research was supported in part by Research Grants from the
Ministry of Health, Labor, and Welfare, Japan. There are no conflicts
of interest.
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