Association of Single Measurement of dipstick proteinuria with physical performance of military males: the CHIEF study RESEARCH ARTICLE Open Access Association of Single Measurement of dipstick proteinuria with physical performance of military males: the CHIEF study Chia-Hao Fan1, Ssu-Chin Lin1, Kun-Zhe Tsai2, Tsung-Jui Wu2, Yen-Po Lin3, Yu-Kai Lin2,4, Shao-Chi Lu2, Chih-Lu Han5 and Gen-Min Lin2,4,6* Abstract Background: Proteinuria, a marker of kidney injury, may be related to skeletal muscle loss. Whether the severity of proteinuria is associated with physical performance is unclear. Methods: We examined the association of proteinuria severity with physical performance cross-sectionally in 3357 military young males, free of chronic kidney disease, from the cardiorespiratory fitness and hospitalization events in armed Forces (CHIEF) study in Taiwan. The grades of proteinuria were classified according to one dipstick urinalysis which were collected at morning after an 8-h fast as unremarkable (0, +/−, and 1+), moderate (2+) and severe (3+ and 4+). Aerobic physical performance was evaluated by time for a 3000-m run and anaerobic physical performance was evaluated by numbers of 2-min sit-ups and 2-min push-ups, separately. Multiple linear regressions were used to determine the relationship. Results: As compared with unremarkable proteinuria, moderate and severe proteinuria were dose-dependently correlated with 3000-m running time (β: 4.74 (95% confidence intervals (CI): − 0.55, 10.02) and 7.63 (95% CI: 3.21, 12.05), respectively), and inversely with numbers of 2-min push-ups (β = − 1.13 (− 1.97, − 0.29), and − 1.00 (− 1.71, − 0.28), respectively) with adjustments for age, service specialty, body mass index, blood pressure, alcohol intake, smoking, fasting plasma glucose, blood urea nitrogen, serum creatinine and physical activity. However, there was no association between proteinuria severity and 2-min sit-ups. Conclusions: Our findings show a relationship of dipstick proteinuria with aerobic physical performance and parts of anaerobic physical performance in military healthy males. This mechanism is not fully understood and requires further investigations. Keywords: Proteinuria, Physical performance, Military male adults © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. * Correspondence: farmer507@yahoo.com.tw 2Department of Medicine, Hualien Armed Forces General Hospital, No. 163, Jiali Rd., Xincheng Township, Hualien 97144, Taiwan 4Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Full list of author information is available at the end of the article Fan et al. BMC Nephrology (2020) 21:287 https://doi.org/10.1186/s12882-020-01948-w http://crossmark.crossref.org/dialog/?doi=10.1186/s12882-020-01948-w&domain=pdf http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/publicdomain/zero/1.0/ mailto:farmer507@yahoo.com.tw Background Protein is one of the major materials such as the actin and myosin components of sarcomere constituting skel- etal muscle fibers in the body [1]. Under normal condi- tions, protein loss is less than 150 mg per day and excreted by the kidney in healthy adults [2]. Proteinuria is defined as excess proteins excreted in the urine and commonly observed in several clinical situations [3]. Pathological proteinuria is related to urinary tract abnor- malities (e.g. hematuria), systemic inflammation, dia- betes, hypertension, malignancies, dehydration, drugs and chronic kidney disease [4–6]. By contrast, physio- logical proteinuria is usually asymptomatic and associ- ated with intense physical activity, also referred as exercise-induced proteinuria [7, 8]. The pathophysiological mechanisms of proteinuria can be reasoned by an increase of glomerular capillary per- meability to proteins, reduced protein reabsorption in the renal tubules, and overflow of low-molecular-weight proteins [9]. With regard to exercise-induced protein- uria, the main cause is not clarified, but the renin- angiotensin system and prostaglandins are considered to play a major role [10]. The plasma angiotensin II con- centration increases at exercise, possibly resulting in fil- tration of proteins through the glomerular membrane [11]. Strenuous exercises which activate the sympathetic nervous system, secrete catecholamine and produce lac- tate, would increase the permeability of glomerular ca- pillary membrane and related excessive protein excretions as well [12]. In addition, intense physical ac- tivity is at higher risk of rhabdomyolysis and dehydra- tion, and leads to presence of proteinuria [13]. Previous studies have shown that exercise-induced proteinuria is associated with the amount and the length of exercise performed [14]. In an elderly cohort higher albuminuria is a predictor of a decline of physical performance > 2 years [15]. It is important to monitor proteinuria in the general population; however in young adults, the rela- tionship with exercise capacity has not been explored. Military personnel are a special group of young indi- viduals, required to receive intensive training regularly. We hypothesized that presence of proteinuria in military personnel may be related to skeletal muscle injury caused by rigorous training and thus they have poor ex- ercise performance. In this study, we aimed to investi- gate the association of proteinuria severity with physical performance in a military population in Taiwan. Methods Study population The study of cardiorespiratory fitness and hospitalization events in armed forces (CHIEF) was performed in east- ern Taiwan [16–20]. All participants carried out a formal health examination and self-reported a questionnaire for their habits of cigarette smoking and alcohol intake status (current vs. former or never) and physical activity in leis- ure times per week in the past 6 months in Hualien Armed Forces General Hospital. After the health examin- ation, all participants took at least one of the three exer- cise tests including 2-min sit-ups, 2-mininute push-ups, and a 3000-m run at the Hualien Military Physical Train- ing and Testing Center. The study design of CHIEF study has been described in detail previously [19, 21–25]. In 2014, there were 4080 participants receiving the health examination and exercise tests in the study. We excluded 312 males for the BUN > 20 mg/dL or serum creatinine > 1.20 mg/dL, and presence of sediments, casts, crystals, glu- cose, bacteria, positive nitrates, leukocytes and red blood cells in the urine, and the urine specific gravity > 1.020 or < 1.010, leaving a final sample of 3357 males for ana- lysis. In addition, the remaining sample of 411 females were used for a sensitivity test. Anthropometric and blood tests Before taking the laboratory examinations, each partici- pant took his temporal temperature and was interviewed by a military physician. If there were any infection symp- toms or signs along with the body temperature over 37。C, the examinee would be asked to make another appointment while recovery from the sickness to complete the health examination. Anthropometric pa- rameters of body height and body weight were assessed in a standing position of each participant. Body mass index was defined as a ratio of body weight (kilogram) divided by square of height (meter2). Waist circumfer- ence was measured at the midpoint between the highest point of the iliac crest and the last palpable rib. All par- ticipants measured their blood pressure once over right upper arm in a sitting position following a rest for at least 15 min by an automated blood pressure monitor (FT-201, Parama-Tech Co Ltd., Fukuoka, Japan). La- boratory data of blood biochemical tests for blood urea nitrogen (BUN), serum creatinine and fasting plasma glucose were obtained in the morning after a 12-h fast. Dipstick urine examination To avoid a stress status of participants, possibly con- founding the interpretation of proteinuria, the urine sample was collected prior to a venous puncture for drawing the blood sample in the morning. Urine pro- teins were measured using the AUTION dipsticks (ARKRAY. Inc., Shiga, Japan) by a fully automated urine chemistry analyzer (AX-4030, ARKRAY. Inc., Shiga, Japan). On the basis of the clinical classifications recom- mended by the National Kidney Foundation [26], the concentrations of urine proteins of 30–99 mg/dL are de- fined as “1+”, 100–299 mg/dL as “2+”, 300–999 mg/dL as “3+” and ≥ 1000 mg/dL are defined as “4+”. The intra- Fan et al. BMC Nephrology (2020) 21:287 Page 2 of 8 assay coefficient of variation in grading proteinuria was 6.08%. Physical performance assessment Aerobic physical performance was evaluated by 3000-m running time, a strong indicator of the velocity at lactate (anaerobic) threshold [27]. All runs were carried out on a flat playground at 4:00 PM only if the risk coefficient of heat stroke, the product of outdoor temperature (°C) and relative humidity (%) × 0.1, was lower than 40 and no raining. Anaerobic physical performance was separ- ately evaluated by numbers of 2-min push-ups and 2- min sit-ups. The procedures were standardized perform- ing on a sponge pad and scored by computer infrared sensing systems. All testing courses of each participant were monitored by the observing officers and video re- corded. Since the exercise tests are closely related to the rank promotion and military award, the performance is regarded as the best physical fitness of each participant. This study was reviewed and approved by the Institu- tional Review Board of the Mennonite Christian Hospital (No. 16–05-008) in Hualien of Taiwan and written in- formed consent was obtained from all participants. Statistical analysis The severity of proteinuria were classified to 3 groups based on the results of dipsticks as unremarkable (grades: 0, +/−, 1+, N = 2011), moderate (grades: 2+, N = 1058) and severe (grades: 3+ and 4+, N = 288). The char- acteristics of subjects were expressed as mean ± standard deviation (SD) for continuous data, and numbers with percentages for categorical data. The relationship of moderate and severe proteinuria with the performance in each exercise (i.e., time for a 3000-m run, numbers of 2-min push-ups and numbers of 2-min sit-ups) were in- vestigated by using analysis of covariance (ANCOVA), and the results were expressed as mean ± standard error (SE). Multiple stepwise linear regression analyses of each exercise performance with moderate and severe protein- uria, relative to unremarkable proteinuria, were also per- formed as the main analysis. Since the performance in each exercise was centrally distributed (supplemental Figure), it might not be appropriate using the linear re- gression analysis to evaluate the possibility of remarkable proteinuria for the highest or lowest physical perform- ance. Therefore, multiple logistic regression analyses were used to determine the odds ratio (OR) of being the superior (highest 10th percentile) and the inferior (low- est 10th percentile) performers in each exercise with moderate and severe proteinuria compared to unremark- able proteinuria (secondary analysis). The levels for the superior/inferior performances in each exercise were al- ternatively set as 5 and 16% for a comparison with 10%. In model 1, age and military service specialty were ad- justed. In model 2, body mass index, BUN and serum creatinine were additionally adjusted. In model 3, sys- tolic blood pressure, fasting plasma glucose, smoking status, alcohol intake status and physical activity were further adjusted. These potential confounders for the models were chosen based on prior published associa- tions with physical performance [28] and those with a significant difference among the groups. A value of p < 0.05 was considered significant. Statistical analyses were done with a standard program (Statistical Package for Social Sciences, SPSS, version 25.0). Results Subject characteristics The subject characteristics of each group are revealed in Table 1. The males with unremarkable proteinuria had relatively older ages, greater body mass index and waist circumference, a lower prevalence of current cigarette smokers, and lower concentrations of BUN, serum cre- atinine and fasting plasma glucose than those with mod- erate and severe proteinuria. On the contrary, the males with severe proteinuria had a higher level of systolic blood pressure and higher concentrations of BUN, serum creatinine and fasting plasma glucose than those with unremarkable or moderate proteinuria. Group means comparisons Table 2 shows the number of military males specifically for an exercise test and the mean of physical perform- ance in the three proteinuria groups. There were signifi- cant differences in 3000-m running time (857.2 s vs. 861.5 s vs. 873.0 s, p < 0.01) and 2-min push-ups num- bers (49.6 vs. 48.5 vs. 47.5, p < 0.01) among the unre- markable proteinuria, moderate proteinuria, and severe proteinuria groups after adjusting for all covariates in model 3. However, there were similar 2-min sit-ups numbers among the three proteinuria groups in models 1–3. In addition, since there was only one young female categorized in the moderate proteinuria group, the mod- erate and severe proteinuria groups were combined to the remarkable proteinuria group in the sensitivity ana- lysis which demonstrated similar tendencies for each physical performance, despite statistically insignificance (supplemental Table 1). Multiple linear regressions The results of multiple linear regressions of each exer- cise performance, with moderate and severe proteinuria relative to unremarkable proteinuria, shown in Table 3 are consistent with the findings of ANCOVA in Table 2. As compared with unremarkable proteinuria, moderate proteinuria and severe proteinuria were dose- dependently and positively correlated with time for a Fan et al. BMC Nephrology (2020) 21:287 Page 3 of 8 3000-m run (β =4.74 and 7.63; p-values =0.07 and < 0.01, respectively) and inversely with 2-min push-ups num- bers (β = − 1.13 and − 1.00; both p-values < 0.01, respect- ively) in model 3. However, moderate proteinuria and severe proteinuria were not correlated with 2-min sit- ups numbers in models 1–3. The sensitivity test for fe- males also showed similar tendencies in each physical performance, despite insignificance in models 1–3 (sup- plemental Table 2). Multiple logistic regressions The results of multiple logistic regressions of the best 10% and the worst 10% performances in each exercise, with moderate and severe proteinuria relative to unre- markable proteinuria, are shown in Table 4. As com- pared to those with unremarkable proteinuria, the males with moderate proteinuria and the males with severe proteinuria were more likely to be the worst 10% performers in the 3000-m run test in models 3 (OR = 1.30 and 1.93, respectively). In addition, the males with severe proteinuria but not the males with moderate pro- teinuria were more likely to be the worst 10% per- formers in the 2-min push-ups test (OR: 1.77). On the contrary, the males with moderate proteinuria and the males with severe proteinuria were not associated with the performances in 2-min sit-ups in models 1–3. The results of multiple logistic regressions of the best and the worst performances in each exercise at the level of 5 and 16%, respectively with moderate and severe protein- uria relative to unremarkable proteinuria, are in line with that at the level of 10%, which are shown in supple- mental Table 3. Discussion Our principal findings were that more severe proteinuria in one urine dipstick test was associated with lower Table 1 Baseline Characteristics of the Study Cohort (n = 3357) Characteristics Unremarkable Proteinuria (n = 2011) Moderate Proteinuria (n = 1058) Severe Proteinuria (n = 288) p-value Age (years) 29.80 ± 5.60 28.92 ± 6.13 27.89 ± 5.99 < 0.01 Specialty, n (%) Army 989 [49.2] 547 [51.7] 146 [50.7] 0.03 Navy 474 [23.6] 197 [18.6] 63 [21.9] Air force 548 [27.2] 314 [29.7] 79 [27.4] Body mass index (kg/m2) 25.04 ± 3.00 24.63 ± 3.19 24.80 ± 3.21 < 0.01 Waist circumference (cm) 83.83 ± 7.62 82.73 ± 8.34 83.16 ± 8.40 < 0.01 Systolic blood pressure (mmHg) 118.68 ± 12.84 117.64 ± 13.25 119.68 ± 12.85 0.02 Diastolic blood pressure (mmHg) 70.80 ± 9.93 70.22 ± 10.35 70.47 ± 10.45 0.31 Blood test Blood urea nitrogen, BUN (mg/dL) 12.66 ± 2.75 13.25 ± 2.90 13.43 ± 3.17 < 0.01 Serum creatinine (mg/dL) 0.96 ± 0.11 0.97 ± 0.11 0.99 ± 0.12 < 0.01 Fasting plasma glucose (mg/dL) 93.19 ± 12.57 93.43 ± 13.51 96.37 ± 18.93 < 0.01 Alcohol consumption, n (%) Former or never alcohol intake 1151 [57.2] 567 [53.6] 164 [59.6] 0.14 Current alcohol intake 860 [42.8] 491 [46.4] 124 [43.1] Betel nut chewing, n (%) Former or never chewer 1761 [89.0] 912 [87.2] 250 [88.3] 0.34 Current chewer 218 [11.0] 134 [12.8] 33 [11.7] Cigarette smoking, n (%) Former or never smoker 1285 [64.9] 613 [58.6] 165 [58.3] < 0.01 Current smoker 694 [35.1] 433 [41.4] 118 [41.7] Physical activity, n (%) Never or occasionally 404 [20.1] 235 [22.2] 66 [22.9] 0.38 1–2 times/week 773 [38.4] 386 [36.5] 97 [33.7] ≥ 3 times/week 834 [41.5] 437 [41.3] 125 [43.4] Continuous variables are expressed as mean ± standard deviation (SD), and categorical variables as n [%]. Unremarkable proteinuria was defined as dipstick proteinuria grades: 0, +/−, or 1+; moderate proteinuria as grades: 2+; and severe proteinuria as grades: 3+ or 4+ Fan et al. BMC Nephrology (2020) 21:287 Page 4 of 8 cardiorespiratory (aerobic) and part of anaerobic physical performance, particularly for muscular endurance of the chest wall and upper extremities in physically fit male adults with euvolemia and without chronic kidney disease, independent of age, body mass index, kidney function, fasting plasma glucose, cigarette smoking, alcohol intake and physical activity. While the effect sizes may be small, the results are still concerning given the young age and general good health of the study population, especially be- cause proteinuria is suspected to worsen over time. Previous studies have revealed that there was an asso- ciation between muscle wasting and a decrease of renal function. People with chronic kidney disease are predis- posed to muscle wasting and vice versa, those with sar- copenia have a decrease of glomerular filtration rate, which may progress to chronic kidney disease status and result in presence of persistent proteinuria [29–32]. Our findings were in line with this concept by the character- istics of lower body weight and greater BUN and serum creatinine levels which were mainly found in the males with moderate or severe proteinuria. In addition, it is reasonable that decreased muscle mass in the study sub- jects could lead to lower aerobic physical performance and impair part of anaerobic physical performance. Table 2 Differences in Each Exercise Performance 2-min push-ups (numbers) 2-min sit-ups (numbers) 3000-m run (seconds) N Mean (SE) p-value n mean (SE) p-value n mean (SE) p-value Model 1 Unremarkable proteinuria 1996 49.5 (0.2) 0.011 2003 47.7 (0.2) 0.351 1816 857.5 (1.7) < 0.011 Moderate proteinuria 1047 48.7 (0.4) 0.062 1050 47.3 (0.2) 0.202 944 860.3 (2.3) 0.312 Severe proteinuria 288 47.6 (0.7) 0.013 288 47.2 (0.5) 0.333 262 873.8 (4.4) < 0.013 Model 2 Unremarkable proteinuria 1988 49.7 (0.3) < 0.011 1996 47.8 (0.2) 0.181 1810 856.8 (1.6) < 0.011 Moderate proteinuria 1047 48.4 (0.4) < 0.012 1050 47.2 (0.2) 0.102 944 862.2 (2.3) 0.072 Severe proteinuria 288 47.3 (0.7) < 0.013 288 47.0 (0.5) 0.173 262 874.1 (4.3) < 0.013 Model 3 Unremarkable proteinuria 1964 49.6 (0.3) < 0.011 1972 47.7 (0.2) 0.361 1778 857.2 (1.6) < 0.011 Moderate proteinuria 1035 48.5 (0.4) 0.012 1038 47.3 (0.2) 0.182 932 861.5 (2.2) 0.112 Severe proteinuria 282 47.5 (0.7) < 0.013 282 47.2 (0.5) 0.293 256 873.0 (4.2) < 0.013 1Overall p-value; 2Unremarkable proteinuria vs moderate proteinuria; 3Unremarkable proteinuria vs moderate proteinuria Mean ± standard error (SE) for each exercise performance estimated using analysis of covariance with adjustments for Model 1: age and service specialty adjustments; Model 2: the covariates in Model 1, body mass index, BUN and serum creatinine adjustments; Model 3: the covariates in Model 2, systolic blood pressure, fasting plasma glucose, alcohol intake status, cigarette smoking status, and weekly physical activity adjustments Table 3 Multiple Liner Regressions of Dipstick Proteinuria Severity With Each Exercise Performance Moderate proteinuria Severe proteinuria β-value 95% CI p-value β-value 95% CI p-value Model 1 2-min push-ups (n) −0.81 −1.67 – 0.048 0.06 −1.01 −1.74 – − 0.28 < 0.01 2-min sit-ups (n) −0.37 − 0.97 – 0.23 0.22 − 0.26 − 0.77 – 0.24 0.30 3000-m run (sec) 3.18 −2.33 – 8.70 0.25 8.45 3.81–13.08 < 0.01 Model 2 2-min push-ups (n) −1.26 − 2.11 – −0.41 < 0.01 − 1.20 − 1.92 – − 0.48 < 0.01 2-min sit-ups (n) − 0.59 −1.19 – 0.01 0.05 − 0.41 −0.92 – 0.091 0.10 3000-m run (sec) 5.95 0.57–11.33 0.03 8.83 4.32–13.35 < 0.01 Model 3 2-min push-ups (n) −1.13 −1.97 – −0.29 < 0.01 − 1.00 −1.71 – − 0.28 < 0.01 2-min sit-ups (n) − 0.47 − 1.06 – 0.12 0.12 − 0.30 −0.79 – 0.20 0.24 3000-m run (sec) 4.74 −0.55 – 10.02 0.07 7.63 3.21–12.05 < 0.01 Data are presented as βand 95% confidence intervals (CI) using Pearson’s correlation coefficient for Model 1: age and service specialty adjustments; Model 2: the covariates in Model 1, body mass index, blood urea nitrogen and serum creatinine adjustments; Model 3: the covariates in Model 2, systolic blood pressure, fasting plasma glucose, alcohol intake status, cigarette smoking status, and weekly physical activity adjustments Fan et al. BMC Nephrology (2020) 21:287 Page 5 of 8 The other important findings were that higher preva- lence of higher fasting plasma glucose levels and cigarette smoking were observed in those with moderate or severe proteinuria. As is known, exercise induced pro- teinuria has been associated with higher insulin resist- ance [33] which in turn may lead to muscular protein degradations by suppression of Phosphatidylinositol 3- kinase (PI3K)/protein kinase B (Akt) signaling and sub- sequently activation of caspase-3 and the ubiquitin- proteasome proteolytic pathway [34]. In addition, current cigarette smoking can increase inflammation [35] and induce insulin resistance [36], which may lead to muscle wasting, and has been associated with the emergence of dipstick proteinuria in healthy middle aged populations [37, 38]. Therefore, insulin resistance and cigarette smoking may be a mediator for the relationship of proteinuria with lower physical performance. Our study had several advantages. First, the laboratory examinations and the procedures of exercise tests were all performed standardly. Second, a large number of military males were included for the analysis which could provide sufficient power detecting the difference between the groups. Third, 91.5% of the male partici- pants were retained in the analysis that the selection bias would be minimized. Fourth, the daily schedule of mili- tary such as training program was unified so that the bias from unmeasured confounders could be controlled at baseline. However, there were several weak points in this study. First, the presence and grades of proteinuria were measured only by one urine dipstick test, which Table 4 Multiple Logistic Regressions of Dipstick Proteinuria Severity With the Best 10% and the Worst 10% of Each Exercise Performance Moderate proteinuria Severe proteinuria Unremarkable proteinuria OR 95% CI p-value OR 95% CI p-value Ref Top 10% of performance level Model 1 2-min push-ups ≥ 60 numbers 0.96 0.76–1.21 0.71 1.20 0.70–1.50 0.90 1.00 2-min sit-ups ≥ 59 numbers 0.83 0.64–1.07 0.14 0.82 0.54–1.25 0.36 1.00 3000-m run ≤783 s 1.03 0.85–1.25 0.75 0.92 0.66–1.27 0.60 1.00 Model 2 2-min push-ups ≥ 60 numbers 0.90 0.71–1.14 0.39 0.98 0.67–1.43 0.90 1.00 2-min sit-ups ≥ 59 numbers 0.79 0.61–1.02 0.07 0.77 0.50–1.18 0.22 1.00 3000-m run ≤783 s 1.04 0.86–1.26 0.70 0.92 0.67–1.28 0.62 1.00 Model 3 2-min push-ups ≥ 60 numbers 0.94 0.74–1.19 0.58 1.03 0.69–1.52 0.90 1.00 2-min sit-ups ≥ 59 numbers 0.82 0.63–1.06 0.12 0.78 0.50–1.21 0.26 1.00 3000-m run ≤783 s 1.04 0.86–1.26 0.66 0.90 0.65–1.25 0.52 1.00 Bottom 10% of performance level Model 1 2-min push-ups ≤ 37 numbers 1.08 0.85–1.38 0.53 1.70 1.20–2.42 < 0.01 1.00 2-min sit-ups ≤ 40 numbers 1.24 0.96–1.60 0.10 0.87 0.52–1.45 0.59 1.00 3000-m run ≥934 s 1.25 0.96–1.62 0.09 2.01 1.39–2.92 < 0.01 1.00 Model 2 2-min push-ups ≤ 37 numbers 1.16 0.91–1.49 0.23 1.85 1.29–2.69 < 0.01 1.00 2-min sit-ups ≤ 40 numbers 1.26 0.97–1.63 0.08 0.91 0.55–1.53 0.72 1.00 3000-m run ≥934 s 1.31 1.00–1.71 0.04 2.05 1.40–3.01 < 0.01 1.00 Model 3 2-min push-ups ≤ 37 numbers 1.16 0.90–1.49 0.25 1.77 1.23–2.56 < 0.01 1.00 2-min sit-ups ≤ 40 numbers 1.21 0.93–1.57 0.16 0.83 0.49–1.41 0.48 1.00 3000-m run ≥934 s 1.30 0.99–1.69 0.05 1.93 1.31–2.84 < 0.01 1.00 Data are presented as odds ratios (OR) and 95% confidence intervals (CI) using multiple logistic regression analysis for Model 1: age and service specialty adjustments; Model 2: the covariates in Model 1, body mass index, blood urea nitrogen and creatinine adjustments; Model 3: the covariates in Model 2, systolic blood pressure, fasting plasma glucose, alcohol intake status, cigarette smoking status and weekly exercise frequency adjustments Fan et al. BMC Nephrology (2020) 21:287 Page 6 of 8 was easily influenced by many physiological and environ- mental conditions [39]. Second, although numerous co- variates were adjusted, we could not completely avoid the existence of other potential confounders that may lead to a bias. Third, although the statistical differences in the outcome of interests (physical performance) were significant, probably because of the large sample size in this study, the absolute differences were relatively small, which might limit the practical applications. Conclusion Our findings show a dose-dependent relationship of dip- stick proteinuria with aerobic physical performance and part of anaerobic physical performance in military healthy males free of chronic kidney disease. Cigarette smoking and increased insulin resistance may play a po- tential role on the relationship between remarkable pro- teinuria and muscle wasting, leading to impaired physical performance. This mechanism is not fully understood and requires further investigations. Supplementary information Supplementary information accompanies this paper at https://doi.org/10. 1186/s12882-020-01948-w. Additional file 1. Additional file 2. Abbreviations Akt: Protein kinase B; ANCOVA: Analysis of covariance; BUN: Blood urea nitrogen; CHIEF: Cardiorespiratory fitness and hospitalization events in armed forces; CI: Confidence interval; OR: Odds ratio; PI3K: Phosphatidylinositol 3- kinase; SD: Standard deviation; SE: Standard error Acknowledgements None. Authors’ contributions CHF wrote the paper; SCL and TJW collected the data; KZT made the analyses; YPL, YKL, SCL and CLH revised and raised the comments; GML was the principal investigator and made the study design. All authors have read and approved the manuscript Funding The CHIEF study was supported by the grants from the Hualien Armed Forces General Hospital (NO. 805-C108–19 and 805-C109–07), where was the main place involved in the study design, data collection, analyses and writing of this research. Availability of data and materials As the study materials were obtained from the military in Taiwan, the data were confidential and not allowed to be opened in public. If there are any needs for clarification, the readers can contact Colonel Dr. Gen-Min Lin, the corresponding author for sharing the data. Ethics approval and consent to participate The Institutional Review Board (IRB) of the Mennonite Christian Hospital (No. 16–05-008) in Hualien of Taiwan approved access to the data for the CHIEF study, and written informed consent was obtained from all participants. Consent for publication Not Applicable. Competing interests None. Author details 1Department of Nursing, Hualien Armed Forces General Hospital, Hualien, Taiwan. 2Department of Medicine, Hualien Armed Forces General Hospital, No. 163, Jiali Rd., Xincheng Township, Hualien 97144, Taiwan. 3Department of Critical Care Medicine, Taipei Tzu Chi Hospital, New Taipei, Taiwan. 4Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 5Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. 6Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA. Received: 16 October 2019 Accepted: 13 July 2020 References 1. Leung AK, Wong AH, Barg SS. Proteinuria in children: evaluation and differential diagnosis. Am Fam Physician. 2017;95(4):248–54. 2. Carroll MF, Temte JL. Proteinuria in adults: a diagnostic approach. Am Fam Physician. 2000;62(6):1333–40. 3. McConnell KR, Bia MJ. Evaluation of proteinuria: an approach for the internist. 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BMC Nephrology (2020) 21:287 Page 8 of 8 Abstract Background Methods Results Conclusions Background Methods Study population Anthropometric and blood tests Dipstick urine examination Physical performance assessment Statistical analysis Results Subject characteristics Group means comparisons Multiple linear regressions Multiple logistic regressions Discussion Conclusion Supplementary information Abbreviations Acknowledgements Authors’ contributions Funding Availability of data and materials Ethics approval and consent to participate Consent for publication Competing interests Author details References Publisher’s Note