Comparison of muscle strength between subjects with and without proteinuria

We compared the levels of muscle strength between subjects with and without proteinuria. We used data of 721 men and 1063 women, aged 20 79 years, in this cross-sectional investtigation study. Parameters at muscle strength i.e. grip strength, leg strength and leg strength per body weight were evaluated. Proteinuria was measured by urine strip devices. Thirty five men (4.9%) and 27 women (2.5%) were diagnosed as having the proteinuria (+: 30 mg/dl) ≦). Leg strength and leg strength per body weight in men with proteinuria was significantly lower than that in men without proteinuria after adjusting for age. Grip strength in men with proteinuria was also lower than that in men without, but not at a significant level. However such link was not noted in women after adjusting for age. Among Japanese, proteinuria might be a modifiable factor of muscle strength in Japanese men.


INTRODUCTION
Chronic kidney disease (CKD) has become a public health problem in Japan and it is a major risk factor for the end stage renal disease, cardiovascular disease and premature death [1,2].About 20% of adults have CKD, which is defined as kidney damage or a glomerular filtration rate (GFR) <60 ml/min/1.73m 2 for at least three months regardless of cause [3].We have previously showed in a cross-sectional study that the estimated glomerular filtration rate (eGFR) [4] in men with ab-dominal obesity and in women with hypertension was significantly lower than that in subjects without these components of metabolic syndrome [5].In addition, we have also reported that proteinuria was closely linked to lower cardiorespilatory fitness evaluated by ventilatory threshold (VT) [6].
It is also well known that low and declining muscle strength is associated with increased mortality, independent of physical activity and muscle mass [7].In 2006 in Japan, levels of maximal oxygen uptake and muscle strength were recommended as exercise and physical activity reference quantity for health promotion 2006 (EPARQ2006) by the Ministry of Health, Labor and Welfare [8].Although resistance training has been advocated as the most suitable exercise for increasing muscle strength [9,10], the link between proteinuria and muscle strength in a large sample of Japanese has not yet been investigated.
In this study, we investigated muscle strength evaluated by grip strength, leg strength and leg strength per body weight between subjects with and without proteinuria in Japanese.

Subjects
We used all data on 1,784 Japanese (721 men and 1063 women) aged 20 -79 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 muscle strength, urine examination and anthropometric measurements as part of their annual health checkups; and 3) they provided informed consent (Table 1).The study was approved by the Ethics Committee of Okayama Health Foundation.

Anthropometric Measurements
The anthropometric parameters were evaluated by using the following respective parameters such as height, body weight, body mass index (BMI), abdominal circumference, and hip circumference.BMI was calculated by weight/[height] 2 (kg/m 2 ).The abdominal circumference was measured at the umbilical level in standing subjects after normal expiration [11].

Muscle Strength
To assess muscle strength, grip and leg strength were measured [12].Grip strength was measured using THP-10 (SAKAI, Tokyo, Japan), while leg strength was measured by COMBIT CB-1 (MINATO, Osaka, Japan).Isometric leg strength was measured as follows: the subject sat in a chair, grasping the armrest in order to fix the body position.A dynamometer was then attached to the subject's one ankle joint by a strap.The subject extended his or her leg to 60 degrees as described in previous reports [12,13] which have also demonstrated good accuracy for this measurement [13].All muscle strength measurements were recorded in 2 trials, and the better one was employed for analysis.In addition, to standardize the influence of body weight, we calculated the ratio of leg strength to body weight; a ratio of 1.0 in leg strength per body weight has been a standard in past studies [13].

Urine Examination
Urine samples were collected from the second-morning 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+: positive (300 mg/dl) or 4+: positive (1000 mg/dl) by comparison with a standard color chart found on the container's label [14].

Statistical Analysis
All data are expressed as mean ± standard deviation (SD) values.A statistical analysis was performed using an unpaired t test and covariance analysis, where p < 0.05 was considered to be statistically significant.

RESULTS
Clinical profiles are summarized in Table 1.Leg strength was 67.1 ± 17.5 kg in men and 41.5 ± 11.2 in women.Prevalence of proteinuria in enrolled subjects is also summarized in Table 2.A total of 35 men (4.9%) and 27 women (2.5%) was diagnosed as having the proteinuria (+: 30 mg/dl ).≦ We compared muscle strength between subjects with and without proteinuria (Table 3).In men, leg strength and leg strength per body weight in subjects with proteinuria was significantly lower than those in subjects without proteinuria even after adjusting for age by using covariance analysis (leg strength: p = 0.0017, leg strength per body weight: p = 0.0495).The significant differences of grip strength were not noted in men at a significant level (right grip strength: p = 0.3691, left grip strength: p = 0.0670).In women, parameters of muscle strength in subjects with proteinuria were not significant different from those in subjects without roteinuria (Table 3).p

DISCUSSION
In this study, we firstly evaluated the link between proteinuria and muscle strength i.e. grip strength, leg strength and leg strength per body weight in Japanese.Proteinuria might be a modifiable factor of muscle strength, especially in Japanese men.
Proteinuria and/or reduced renal function have been reported to be closely linked to cardio vascular disease (CVD) [15,16].Anavekar et al. showed that even mild renal disease was considered a major risk factor for CVD after myocardial infarction in 14527 patients with acute myocardial infarction [15].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 sig-nificant predictors of CVD and all-cause mortality [16].
We have also reported that proteinuria was a modifiable factor for cardiorespilatory fitness evaluated by VT [6].However, according to the link between proteinuria and muscle strength, there were few studies especially in Japan.Protein-energy wasting is the term proposed to describe the reduction in the stores of energy and protein in patients CKD [17].Muscle wasting is one of the best markers of protein-energy wasting in these patients [18].Leal et al. reported that handgrip strength is a useful tool for continuous and systematic assessment of muscle mass related to nutritional status in patients on dialysis [19].Takhreen reviewed that relationship between exercise intervention and quality of life (QOL) in CKD patients.Exercising patients have shown improvements in physical fitness, psychological function, reaction times and lower extremity muscle strength, and these factors help improve QOL [20].In this study, we solely evaluated the relationship between proteinuria and muscle strength i.e. grip strength, leg strength and leg strength per body weight in the Japanese.The significant differences of leg strength and leg strength per body weight between men with and without proteinuria even after adjusting for age.However, muscle strength in women with proteinuria was not significantly lower than that in women without.Potential limitations still remain in this study.First, our study was a cross sectional and not a longitudinal study.Second, 721 men and 1063 women in our study voluntarily underwent measurements: they were therefore more likely to be health-conscious compared with the average person.Second, we could not show clear mechanism between proteinuria and muscle strength.We have previously reported that brachial-ankle pulse wave velocity (baPWV) in subjects with reduced eGFR was significantly higher than that in subjects without [21].In addition to protein-energy wasting, arterial stiffness might affect the results.Third, significant difference of muscle strength was not noted in women in this study.Low prevalence of proteinuria also affected the results, especially in women.To show this, further prospective studies are needed in the Japanese.

Table 1 .
Clinical profiles of enrolled subjects.

Table 2 .
Prevalence of proteinuria in enrolled subjects.

Table 3 .
Comparison of muscle strength between subjects with and without proteinuria.