Low urine pH associated with sarcopenia in the elderly: A multi-center observational study.

ABSTRACT: The pathophysiology of sarcopenia is complex and must be further explored. While metabolic acidosis may be a risk factor for sarcopenia, it remains unclear whether acidic urine is related to sarcopenia. The purpose of the present study was to investigate the association between sarcopenia and urine pH in the elderly.An elderly population (n = 123 [male = 46]; mean age = 81.7 years) was classified into 2 groups based on the sarcopenia status according to their strength, requirement of assistance in walking, their ability to rise from a chair their ability to climb stairs, and their history of falls. Urinalysis was measured using dipstick tests.The sarcopenia group (n = 32) was significantly older, had less exercise habit and showed a lower urine pH (mean pH = 5.5) in comparison to the nonsarcopenia group (mean pH = 6.2, P < .01). A multivariate analysis that was adjusted for age, male sex, body mass index, uro-renal variables and exercise habit revealed that urine pH (odds ratio, 0.43; 95% confidence interval, 0.22-0.85, P = .02), age and less exercise habit were independently and significantly associated with sarcopenia.The findings of the present study suggest a potential association between metabolic acidosis and the pathophysiology of sarcopenia in the elderly. As urine pH is a simple biomarker that can be obtained using dipstick tests, it is therefore expected to be helpful for detecting sarcopenia in the clinical setting.

Uremic Sarcopenia and Its Possible Nutritional Approach.

Uremic sarcopenia is a frequent condition present in chronic kidney disease (CKD) patients and is characterized by reduced muscle mass, muscle strength and physical performance. Uremic sarcopenia is related to an increased risk of hospitalization and all-causes mortality. This pathological condition is caused not only by advanced age but also by others factors typical of CKD patients such as metabolic acidosis, hemodialysis therapy, low-grade inflammatory status and inadequate protein-energy intake. Currently, treatments available to ameliorate uremic sarcopenia include nutritional therapy (oral nutritional supplement, inter/intradialytic parenteral nutrition, enteral nutrition, high protein and fiber diet and percutaneous endoscopic gastrectomy) and a personalized program of physical activity. The aim of this review is to analyze the possible benefits induced by nutritional therapy alone or in combination with a personalized program of physical activity, on onset and/or progression of uremic sarcopenia.

Relationship between Urinary Liver-Type Fatty Acid-Binding Protein (L-FABP) and Sarcopenia in Spontaneously Diabetic Torii Fatty Rats.

BACKGROUND: Type 2 diabetes (T2D) is a known risk factor for diabetic kidney disease (DKD) and sarcopenia in older patients. Because there may be an interaction between DKD and sarcopenia, the aim of the present study is to investigate the relationship between urinary levels of liver-type fatty acid-binding protein (L-FABP) and sarcopenia using a novel rat model of T2D. METHODS: Male spontaneously diabetic Torii (SDT) fatty rats (n = 5) at 16 weeks of age were used as an animal model of T2D. Age- and sex-matched Sprague-Dawley (SD) rats (n = 7) were used as controls. Urine samples were obtained from the rats, and muscle strength was evaluated with the use of the forelimb grip test at 16, 20, and 24 weeks of age. Serum, kidney, soleus, and extensor digitorum longus (EDL) muscle samples were collected at 24 weeks of age. Urinary L-FABP levels were measured using dedicated enzyme-linked immunosorbent assays. RESULTS: Increased urinary L-FABP levels, focal glomerular sclerosis, moderate interstitial inflammation and fibrosis, and accumulation of renal oxidative proteins were significantly observed in the SDT fatty rats, compared to the SD rats. Muscle weight, muscle strength, cross-sectional areas of both type I and type IIb muscle fibers, and increasing rate of muscle strength were significantly decreased in the SDT fatty rats compared to the SD rats at 24 weeks. Urinary L-FABP levels at 20 and 24 weeks were significantly negatively correlated with muscle strength. Urinary L-FABP levels at 16 weeks were significantly negatively correlated with the increasing rate of muscle strength. CONCLUSIONS: Urinary L-FABP reflects the degree of muscle strength and weight, as well as cross-sectional areas of muscle fibers. Although further clinical study is needed, urinary L-FABP may be useful to monitor the progression of sarcopenia and DKD in T2D patients.

Effect of the Creatinine Excretion Rate Index, a Marker of Sarcopenia, on Prediction of Intracranial Hemorrhage in Patients With Advanced Heart Failure and a Continuous-Flow Left Ventricular Assist Device.

BACKGROUND: Sarcopenia is characterized by progressive loss of skeletal muscle and has frequently been associated with poor clinical outcomes in patients with advanced heart failure (HF). The urinary creatinine excretion rate (CER) index is an easily measured marker of muscle mass, but its predictive capacity for mortality and cerebrovascular events has not been investigated in patients with a continuous-flow implantable left ventricular assist device (CF-iLVAD).Methods and Results:We retrospectively reviewed 147 patients (mean [±SD] age 43.7±12.5 years, 106 male) who underwent CF-iLVAD implantation between April 2011 and June 2019. CER indices in 24-h urine samples before CF-iLVAD implantation were determined. Over a median follow-up of 2.3 years, there were 10 (6.8%) deaths and 43 (29.3%) cerebrovascular events. Patients were divided into 2 groups (low and high CER index) according to the median CER index in men and women (i.e., 13.71 and 12.06 mg·kg-1·day-1, respectively). Mortality and intracranial hemorrhage rates after CF-iLVAD implantation were significantly higher in the low than high CER index group (mortality 12.3% vs. 1.4% [P<0.01]; intracranial hemorrhage 23.3% vs. 8.1% [P=0.01]). Multivariate Cox proportional hazard models revealed that a low CER index was an independent predictor of intracranial hemorrhage in patients receiving a CF-iLVAD (hazard ratio 3.63; 95% confidence interval 1.43-9.24; P<0.01). CONCLUSIONS: A low preoperative CER index is an independent, non-invasive predictor of intracranial hemorrhage after CF-iLVAD implantation.

Muscle mass determined from urinary creatinine excretion rate, and muscle performance in renal transplant recipients.

BACKGROUND: Muscle mass, as determined from 24-h urinary creatinine excretion rate (CER), is an independent predictor for mortality and graft failure in renal transplant recipients (RTR). It is currently unknown whether CER is comparable with healthy controls after transplantation and whether it reflects muscle performance besides muscle mass. We aimed to compare urinary CER and muscle performance between RTR and healthy controls and to investigate whether urinary CER is associated with muscle performance in RTR. METHODS: We included RTR, transplanted between 1975 and 2016 in the University Medical Center Groningen. Healthy controls were subjects screened for kidney donation. CER was calculated from a 24-h urine collection. Muscle performance was assessed by handgrip strength, sit-to-stand test, and 2-min walk test. Statistical analyses were performed using linear regression analyses. RESULTS: We included 184 RTR (mean age 56.9 ± 11.9 years, 54% male recipient) and 78 healthy controls (age 57.9 ± 9.9, 47% male recipient). RTR were at a median time of 4.0 (1.1-8.8) years after transplantation. Mean CER was lower in RTR compared to healthy controls (11.7 ± 4.0 vs. 13.1 ± 5.2 mmol/24 h; P = 0.04). Significantly poorer results in muscle performance were found in RTR compared to controls for the handgrip strength (30.5 [23.7-41.1] N vs. 38.3 [29.3-46.0] N, P < 0.001) and the 2-min walk test (151.5 ± 49.2 m vs. 172.3 ± 12.2 m, P < 0.001) but not for the sit-to-stand (12.2 ± 3.3 m vs. 11.9 ± 2.8 m, P = 0.46). In RTR, CER was significantly associated with handgrip strength (std. ß 0.33; P < 0.001), independent of adjustment for potential confounders. In RTR, CER was neither associated with the time used for the sit-to-stand test (std. ß -0.09; P = 0.27) nor with the distance covered during the 2-min walk test (std. ß 0.07; P = 0.40). CONCLUSIONS: Muscle mass as measured by CER in RTR is lower compared to controls. CER is positively associated with muscle performance in RTR. The results demonstrate that CER does not only reflect muscle mass but also muscle performance in this patient setting. Determination of CER could be an interesting addition to the imaging technique armamentarium available and applied for evaluation of muscle mass in clinical intervention studies and observational studies.

Correlation between the 24-h urinary angiotensinogen or aldosterone level and muscle mass: Japan shimanami health promoting program study.

Our previous report indicated that sarcopenia is associated with arterial stiffness and cardiovascular death. The renin-angiotensin system (RAS) plays an important role in cardiovascular disease and its activation may be correlated with sarcopenia according to basic research. However, few clinical studies have assessed the correlation between skeletal muscle loss and RAS component concentrations in healthy subjects. The purpose of this study was to investigate the relationships between the excretion of angiotensinogen (AGT) and aldosterone (Ald) in 24-h urine samples and clinical and sarcopenic indices. A total of 344 people participated in a voluntary medical check-up program, "Anti-Aging Doc", and underwent measurement of their sarcopenia-related indices. Urine samples were collected for 24-h within 8 weeks after a medical check-up using a partition cup and a proportional sampling method. Urine AGT and Ald levels were evaluated by enzyme-linked immunosorbent assay (ELISA). After compensating for possible confounding parameters, including baPWV, the 24-h urinary excretion of AGT was independently and negatively associated with the thigh muscle cross-sectional area. On the other hand, urinary Ald excretion was not associated with sarcopenia-related indices after compensation, even though it showed a modest but significantly positive association with sarcopenic indices in single regression analysis. Urinary AGT was related to sarcopenic indices and may be involved in the pathogenesis of sarcopenia. On the other hand, urinary Ald was not related to sarcopenic indices when considering other risk factors.

Sarcopenia associated with renal function in the patients with type 2 diabetes.

AIMS: Studies have suggested that low muscle mass is associated with declining renal function in healthy populations, whether the association is relevant to patients with type 2 diabetes is not well understood. This study investigates the association between sarcopenia and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratios (UACR) in the patients with type 2 diabetes. METHODS: Two recruited groups consisted of 793 persons without diabetes (males/females=550/243) and 762 persons with type 2 diabetes (males/females=501/261). RESULTS: The non-sarcopenia population demonstrated higher ASM/HT(2), GFR (P<0.001) and lower UACR (P＜0.05) than the sarcopenia population. In studied men, the association between ASM/HT(2) and eGFR was statistically significant in the group without diabetes (OR=0.580, P=0.020), a trend which persisted in women (OR=0.491, P=0.014). The association between ASM/HT(2) and UACR persisted in studied women of two groups (OR=0.269, P=0.005; OR=0.405, P=0.008, respectively). The highest quartile of ASM/HT(2) in the non-sarcopenia population exhibited a 3.753-fold risk of abnormal eGFR within the diabetes group (OR=3.753, P=0.020). The cutoff point of ASM/HT(2) to indicate abnormal renal function for population with non-sarcopenia was 6.32kg/m(2) in the group without diabetes and 6.31kg/m(2) in diabetes group. CONCLUSIONS: Sarcopenia is associated with declining renal function, which induces lower eGFR and higher UACR. In the non-sarcopenia population, ASM/HT(2) presents as renal function risk factor, which perhaps associated with higher muscle mass to induce a greater underestimation for creatinine and urinary albumin.

Mid-adulthood cardiometabolic risk factor profiles of sarcopenic obesity.

OBJECTIVE: Midlife and contemporaneous cardiometabolic risk factors associated with sarcopenic obesity were examined. METHODS: Utilizing BMI and sex-specific 24-h urinary creatinine excretion, 1,019 participants from the Framingham cohorts were categorized as non-sarcopenia non-obese (NSNO), non-obese sarcopenia, non-sarcopenic obesity, and sarcopenic obesity. Cardiometabolic risk factors were quantified by standard laboratory assessment cross-sectionally and 10, 20, and 30 years before sarcopenic obesity assessment. RESULTS: NSNO, sarcopenia, obesity, and sarcopenic obesity accounted for 30.0%, 39.6%, 20.0%, and 10.4% of study participants, respectively. Cross-sectionally, participants with sarcopenic obesity had a higher proportion of hypertension, metabolic syndrome, and type 2 diabetes than those with NSNO or sarcopenia (all P < 0.03). Similar patterns were observed retrospectively at 10, 20, and 30 years. Compared with NSNO or sarcopenia, sarcopenic obesity was associated with a higher prevalence of type 2 diabetes at 10 years and hypertension and metabolic syndrome at all three time points before baseline (all P < 0.03). Individuals with sarcopenic obesity had more type 2 diabetes than those with obesity alone at baseline and 10 years prior (all P < 0.001). CONCLUSIONS: Older adults with sarcopenic obesity had more adverse midlife cardiometabolic risks, particularly diabetes 10 years earlier, which suggests the importance of early identification of risk factors associated with sarcopenic obesity.

Gender-specific association between urinary sodium excretion and body composition: Analysis of the 2008-2010 Korean National Health and Nutrition Examination Surveys.

OBJECTIVE: Few studies have reported the relationship between sarcopenia and the estimated amount of sodium excreted in 24 h, as measured by the spot urine test (E24UNA), in a community-dwelling cohort. We investigated the gender specific association between E24UNA values and body composition indices. MATERIALS AND METHODS: Data from a total of 7162 participants (3545 men and 3617 postmenopausal women) aged 45 years or older were obtained from multiple Korea National Health and Nutrition Examination Surveys (2008-2010) and analyzed. The total amount of sodium excreted in the urine in a 24-h period was estimated with spot urine specimens. Sarcopenia was defined as an appendicular skeletal muscle mass divided by body weight (ASM/Wt) that was less than 1 standard deviation below the sex-specific mean for young adults. RESULTS: E24UNA values were positively correlated with body mass index, waist circumference, total fat mass, and blood pressure; in contrast, E24UNA values were negatively correlated with ASM/Wt in both sexes. Compared with those in the lowest E24UNA tertile, participants in the highest E24UNA tertile were at higher risk for sarcopenia (men: odds ratio (OR)=1.3 [95% confidence interval (CI)=1.07-1.59]; women: OR=1.41 [95% CI=1.16-1.73]). Further classification of subjects with sarcopenia into sarcopenic obese and sarcopenic nonobese groups revealed that the highest E24UNA values were found in the sarcopenic obese group; this difference was statistically significant. The next highest levels were found in the sarcopenic nonobese group, followed by the nonsarcopenic group. This trend was observed in both sexes. CONCLUSION: High E24UNA values were independently associated with both sarcopenia and obesity in Korean individuals older than 45 years. These results suggest that high salt intake may have a deleterious effect on body composition.

Creatinine excretion rate, a marker of muscle mass, is related to clinical outcome in patients with chronic systolic heart failure.

AIMS: In chronic heart failure (CHF), low body mass as a reflection of low muscle mass has been associated with poor outcome. Urinary creatinine excretion rate (CER) is an established marker of muscle mass, but has not been investigated in CHF. This study aims to evaluate urinary CER as a marker of muscle mass in patients with CHF and establish the relationship with clinical outcome. METHODS AND RESULTS: In 120 patients with CHF, we evaluated CER as determined by mean creatinine excretion rate in two consecutive 24-h urine collections. We evaluated the relationship between CER and clinical variables using linear regression. Finally, we evaluated the association between CER and clinical outcome. Mean age was 59 ± 12 years, and 80% were male. Mean CER was 1,383 mg/day (range 412-2,930). Independent predictors of CER were body surface area (BSA) (ß = 0.404, P < 0.001), gender (ß = -0.180, P = 0.029), log N terminal pro-brain natriuretic peptide (NTproBNP) (ß = -0.172, P = 0.048) and age (ß = -0.168, P = 0.035). During three years of follow-up, 33 patients (28%) developed a clinical endpoint, defined as the first occurrence of either all-cause death, heart transplantation, myocardial infarction, or hospitalization for heart failure during three years of follow-up. In Cox regression analyses, log CER was associated with the occurrence of the clinical endpoint independent of age, gender, BSA, glomerular filtration rate and urinary albumin excretion, [hazard ratio 7.67 (1.82-32.3) per log decrease], but not independent of NTproBNP [hazard ratio 3.66 (0.79-17.0), P = 0.098]. CONCLUSIONS: Low urinary CER is associated with smaller body dimensions and more severe heart failure and is associated with an increased risk of adverse outcome.

Urine melatonin levels are inversely associated with sarcopenia in postmenopausal women.

OBJECTIVE: Mainly secreted in the pineal gland, melatonin is a neurohormone that has versatile functions, including cellular protection. Decreased melatonin levels are associated with the aging process and age-related conditions. Melatonin may be associated with sarcopenia because it is one of the most common age-related diseases and because disrupted cellular vitality in skeletal muscle is known to be involved in its pathogenesis. Therefore, we investigated the relationship between first-morning-urine 6-sulfatoxymelatonin (aMT6s) levels and sarcopenia in Korean postmenopausal women. METHODS: Seventy-eight Korean postmenopausal women participated. Biomarkers of metabolic risk factors, along with the presence of sarcopenia, were assessed using dual-energy x-ray absorptiometry. Urine aMT6s levels were measured using enzyme-linked immunosorbent assay. RESULTS: The prevalence of sarcopenia increased significantly with increasing aMT6s quartiles. Furthermore, multivariate logistic regression analysis showed that the fourth aMT6s quartile was associated with sarcopenia, with an adjusted odds ratio of 0.13 (95% CI, 0.03-0.70; P = 0.02). CONCLUSIONS: Our study shows an inverse association between urine melatonin and sarcopenia, suggesting that melatonin may have a protective role in the pathophysiology of sarcopenia. Further studies are required to better understand the clinical significance of our findings.