How To Prevent Frailty: Improve Renal Function Is The Key

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Nutritional Status and Renal Function in Relation to Frailty among the Community-Dwelling Elderly Taiwanese Population

C.-Y.Changi, M.-H.Lin, C.-C.Kuo, C.-H.Lue, D.-M.We, M.-K, saiN-E.Chue

Abstract

OBJECTIVES: Frailty is a significant public health and clinical issue among the elder population. This study aimed to evaluate the nutritional status and renal function in relation to frailty among elderly Taiwanese.

DESIGN: We administered community-based health surveys to the elder population in Chiayi County, Taiwan, from 2017 to 2019. MEASUREMENTS: We measured nutritional status(including serum albumin and total protein levels), renal function (including serum blood urea nitrogen. creatinine, urine protein, and urine creatinine levels), handgrip strength(GS) and calculated appendicular muscle mass(AMM).

RESULTS: The study recruited 3739 participants (2139 women). Participants of both sexes with normal GS had higher serum albumin levels and lower urine protein/creatinine ratios (UPCRs).For the men with normal and weak GS, serum albumin levels were 4.15±0.2 and 4.10±0.2g/dL(p<0.01),and UPCRs were 123.1±219.6 and 188.7 ± 366.2(p< 0.001),respectively. GS was positively correlated with serum albumin and urine creatinine levels (r=0.136 and O.177. both p<0.001).AMM was also positively correlated with serum albumin and urine creatinine levels(r= 0.078 and 0091, both p<0.001).In the multivariate regression model, for every 1 g/dL increase in serum albumin level, there was a 1.9 and 1.7-kg increase in GS for men and women (p<0.05 and p<0.01), respectively. The final model for predicting GS included age, albumin, BUN, and UPCR(urine creatinine for women)which presented a variance of 22.1% and 13.8%, respectively.

CONCLUSION: Proper dietary nutritional intake and maintaining renal function are key elements for preventing frailty among the elder population in Taiwan.

Keywords: Nutritional status, renal function, grip strength; appendicular muscle mass, frailty.

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Introduction

sarcopenia Frailty has become a major public health issue over the past decades due to the rapid D) increase among the aging population(1,2). Frailty is generally defined as decreased resistance to stressors resulting from functional decline in multiple organ systems, causing vulnerability to unfavorable outcomes(3,4). Elder individuals with frailty have more negative health outcomes including falls and fractures, loss of activities of daily living, more hospitalizations, and early mortality (5,6).

Sarcopenia, defined as age-related loss of muscle function and mass(7,8), is one of the main components of frailty(3, 5). As an indicator of muscle function, grip strength(GS)is used to screen for sarcopenia because it better predicts unfavorable outcomes(8,9). Measuring GS is a simple, quick, and inexpensive method for determining overall muscle strength and is a good indicator of fragility(10,11). Although sarcopenia is also associated with muscle mass, access to instrumentation and technical difficulties in accurately measuring muscle mass have become problematic issues in clinical practice settings (8,12,13). In this paper, we offer an alternative to instrumental studies by using an equation to estimate appendicular muscle mass(AMM), which provides an easier and more affordable method for evaluating muscle mass (14).

Serum albumin is one of the most abundant and commonly measured serum proteins and nutrition status(15). Hypoalbuminemia is considered an indicator of poor nutritional status(15)and a marker for poor health outcomes such as mortality and disability(16). Several studies have focused on the association between sarcopenia and albumin levels but have shown inconsistent results (17-19).

Previous studies have also demonstrated that sarcopenia is a common finding in patients with chronic kidney disease (CKD)(20), and the prevalence of CKD-related sarcopenia is higher than that observed in age-related sarcopenia(21). However, studies on the correlation between sarcopenia and renal function biomarkers have obtained conflicting results (20, 22).

The aim of our study was to evaluate the relationship between nutritional status, renal function, and frailty among the elder Taiwanese population. Based on the correlation between frailty and these biomarkers, we try to establish a prediction model to identify individuals with increased risk of frailty with the aim of offering an earlier and more effective health promotion program.

Materials and Methods

Study population

We conducted a series of community-based health surveys among elder individuals in Chiayi County, Taiwan, from 2017 to 2019. We invited those older than 65 years who had lived in Chiayi County for more than one year to participate in the study. The inclusion criteria were an age of 65-85 years and no infectious disease or acute disorders in the past three weeks preceding the start of the surveys.

Questionnaire

Data on general demographics and lifestyle patterns(such as dietary patterns, smoking status, and alcohol intake) were collected using a standard structured questionnaire. Information on disease status(such as diabetes mellitus, hypertension, cardiovascular disease, stroke, chronic kidney disease, hyperlipidemia, and certain types of cancer) was also obtained from the questionnaire and medical records. A trained research technician administered the questionnaires to obtain the participant's history of chronic diseases. The participants were asked the following questions: "Was there a doctor who told you that you had a disease such as [name of the disease]?" and "Do you regularly take medications for a chronic disease?"

Anthropometric measurements

The anthropometric characteristics(including body weight, height, and waist circumference) were measured using standard methods. Height was measured in meters using a digital stadiometer that recorded to the nearest 0.5 cm, with the participants barefoot and wearing only light indoor clothing. Bodyweight was measured to an accuracy of 0.1 kg using a standard beam balance scale. Waist circumference was measured using standard methods suggested by the World Health Organization. Waist circumference was measured to the nearest 0.1 cm at the midpoint between the margin of the last rib and the iliac crest of the ilium. We calculated the body mass index as body weight (kg)divided by the height squared (m).

Estimated appendicular muscle mass(AMM)

AMM was estimated using the following equation that included hand GS, weight, sex,and height: AMM =-9.833 + 0.397× weight (kg)+4.433 ×sex+ 0.121× height (cm)+ 0.061 × hand GS (kg). This equation best predicts AMM measured by dualenergy X-ray absorptiometry(adjusted R:=0.914, standard error of the estimate = 2.062,P< 001)(14).

Grip strength measurement

The GS was measured using a dynamometer (TKK 5101 Grip-D. Takey, Tokyo, Japan), a digital tool with an adjustable grip span, a range of 3.5-7.0 cm, a precision of 0.1 kg, and the ability to measure 5-100 kg (23). All participants were seated according to the procedure described by Espana-Romero et. (24), with the elbows fully extended. We then measured the dominant hand's GS after 2-3 min of rest. Two GS values were recorded, and the mean value of the two recordings was used for the analysis (25).

Blood and urine specimen collection and analysis

After 10-12 h of overnight fasting,10 mL of venous blood was collected from the participants using a venous container. The serum was separated from the blood within 1 h and stored at -80°C until analysis. Spot urine was collected for the first voided urine on the same morning.

We measured serum total protein levels using the biuret method, serum albumin levels using the bromocresol green method, serum blood urine nitrogen (BUN)levels using the glutamate dehydrogenase enzymatic method, and serum creatinine levels using the modified Jaffe's kinetic method. For urine, we measured total protein levels using the pyrogallol red method, urine BUN levels using the glutamate dehydrogenase enzymatic method, and urine creatinine levels using the modified Jaffe's kinetic method.

We calculated the estimated glomerular filtration rate (eGFR)using the modification of diet in renal disease equation, calculated the serum albumin/protein ratio(APR)as a surrogate marker for general nutritional status, and calculated the urine protein/creatinine ratio(UPCR) as a surrogate marker for urine protein secretion status and renal function.

Statistical methods

We used SPSS version 22(IBM Corporation, New York, USA)to conduct all statistical analyses. The continuous variables(such as anthropometric measures, GS, nutrition status, and renal function)are presented as sample means and SD. We employed the Mann-Whitney U test to compare the differences between the groups and the Kruskal-Wallis H test to compare more than three groups, The categorical variables are described as numbers and percentages. We employed the chi-squared test to compare the differences between two or more groups. We used correlation coefficient and multivariate regression analyses for further statistical inferences. A two-tailed p-value< 0.05 was considered statistically significant.

Results

We enrolled 3739 participants(1600 men and 2139 women)whose anthropometry characteristics, nutritional status, and renal function by GS subgroup are shown in Tables 1 and 2. For the nutritional profile, the participants with normal GS had higher serum albumin levels and higher serum APRs for both sexes. For the men with normal and weak GS, the serum albumin levels were4.15±0.2 and4.10±0.2g/dL(p<0.001), and the APRs were 0.571±0.031 and0.567±0035(p<0.05). respectively. For the women with normal and weak GS.the serum albumin levels were 4.14±0.2 and 4.11±0.2g/dL(p<0.001).and the APRs were 0.566±0.030 and 0.563±0.034(p <0.05), respectively. For renal function, the participants with normal GS had lower UPCRs and higher eGFRs for both sexes. For the men with normal and weak GS, the UPCRs were 123.1 ± 219.6 and 188.7 ± 366.2(p<0.001), and the eGFRs were 64.4± 12.9 and 61.6±15.5(p<0.001), respectively. For the women with normal and weak GS, the UPCRs were 145.3 ±363.8 and 172.6±380.5(p<0.001), and the eGFRs were 64.0 ±13.1 and 62.2±14.9(p<0.001), respectively. The estimated AMMs were higher for the participants of both sexes with normal GS(43.5±4.3 for normal GS to 40.0±4.2kg for weak GS[p<0.001] for the men and 24.4± 3.3 for normal GS to 16.6± 2.5 kg for weak GS [p<005] for the women).

Table 1. Characteristics of anthropometry, nutrition status, kidney function, chronic disease, and grip strength among the community-based population in male elder population (n=1,600)	Table 2. Characteristics of anthropometry, nutrition status, kidney function, chronic disease, and grip strength among the community-based population in female elder population (n=2,139)

Table 3 demonstrates the Spearman correlation between GS and the anthropometric characteristics, nutritional status, and renal function. For nutritional status, GS was positively correlated with serum albumin levels (r= 0.136, p <0.001 for the men and r= 0.100,p < 0.001 for the women)and serum APR (r=0.060,p<0.05 for the men andr=0.062,p<0.01 for the women), AMM was positively correlated to serum albumin levels(r = 0.177 [p< 0.01] for the men and r= 0.103 [p<O001] for the women) and total protein levels (r= 0086 [p<0.01]for the men and r= 0.085 [p<0.001] for the women).For renal function,GS was negatively correlated to serum creatinine levels for both sexes (r=-0.095 [p <0.001] for the men and r = -0.046 [p<0.05] for the women).GS was also positively correlated to eGFR (For men,r =0.096, p<0.001 for the men and for women, r= 0.065,p <0.01).

Table 3. Correlation between grip strength and anthropometry, nutrition status, kidney function among the community-based population with gender specifications (n=3,739)

In the multivariate regression model, we noticed that for every 1 g/dL increase in serum albumin level, there was a 19 and 1.7-kg increase in GS for the men and women (p <005 and p<0.01), respectively (Table 4). For the men,GS was also negatively associated with BUN(β=-0.064,p<0.05), urine protein (β=-0.020,p<0.001)and UPCR(β=-0.002, p<0.001). For the women, GS was positively associated with serum albumin to protein level(β= 6.759,p< 0.05)and negatively associated with eGFR(β=-0.017.p<0.05). In contrast, the estimated AMM for the men was positively associated with serum albumin(β = 0.805,p<0.05)and urine creatinine levels(β= 0.004, p<0.001)and negatively associated with UPCR(β=-0.001,p<0.01).

Table 5 shows the GS level determined by nutrition status and renal function. In the final model, we included age, serum albumin level, serum BUN level, and UPCR, which determined almost 22.2% of the GS (R'=0.221)for men. For women, age, serum albumin level, serum BUN level, and urine creatinine level determined 13.8% of the GS(R2=0.138).

Table 4. Multiple regression coefficients for each nutrition status and kidney function variables on grip strength and appendicular Muscle Mass with gender specifications (n=3,739)	Table 5. Multiple regression coefficients for each nutrition status and kidney function variables on grip strength with gender specifications (n=3,739)

Discussion

The present study demonstrated that nutritional status (such as serum albumin level) was positively associated with GS for both sexes. The favorable renal biomarkers are also positively correlated to GS. For the final model, we combined age, albumin, BUN, UPCR(or urine creatinine for the women)to predict the GS of the elderly Taiwanese population.

There are a number of limitations to our study. First, the cross-sectional design limits our ability to evaluate causal relationships between sarcopenia, frailty, nutritional status, and renal function among an elderly population. Second, an information bias regarding the participants' history of chronic diseases cannot be ruled out when using a survey questionnaire. Lastly, we employed nutrition status and renal function into equations to estimate GS. Although these evidence-based equations provided a convenient method in the public health realm, the ability to predict GS is still low. However, the association between nutritional status, renal function, frailty, and sarcopenia was still reliably explored in this study.

The correlation of nutrition status and renal function was stronger and more consistent with the GS than estimate AMM in the current study. Further surveys designed for instrumental measured AMM may provide further evidence and we will focus on the relation between nutrition status, renal function, and GS in the following discussion.

In our study, the serum albumin level was positively correlated to GS in both sexes. In the Longitudinal Aging Study Amsterdam (LASA)(17), low serum albumin levels were independently associated with weaker muscle strength. In the male population of kidney transplant recipients, serum albumin levels also predict hand GS (26). Several studies have shown that there is a positive association between albumin levels and muscle mass among elderly populations(27,28).In the United States, however, a prospective cohort study that included 5534 male participants from six US academic medical centers found that albumin levels showed modest and inconsistent trends with the loss of muscle mass and function(18). The above studies were almost all conducted in western countries and had significant ethnic differences when compared with our study population. Longitudinal studies on Asian populations should be considered for further investigations. To the best of our knowledge, no study has demonstrated the relationship between GS, APR, and albumin/globulin levels. In our study, however, the association between GS and APR was only significant in women. The further study focused on sarcopenia and more detailed serum protein composition should be considered.

The associations between muscle mass, muscle strength, and kidney function were inconsistent in our study, in which participants with normal GS had better renal function (such as lower serum creatinine levels, higher eGFR, and lower UPCR)compared with the group with weak GS. Better renal function also appeared to be associated with greater GS. After adjusting for other dependent variables, however, the associations became statistically insignificant. Although previous studies have demonstrated that sarcopenia is a common finding in patients with CKD(20,22) the direct relationship between biomarkers and GS was not significant even in elderly patients with advanced kidney disease (29). However, the overall prevalence of CKD in our study population was relatively low, and therefore the impact of renal function on sarcopenia might be diluted toward insignificance.

Other studies have focused on the correlation between renal function and sarcopenia and have demonstrated that GS was positively associated with cystatin C-based eGFR rather than creatinine-based eGFR (30,31). Future studies focusing on the relationship between GS and renal function using alternative biomarkers among individuals with varying CKD status might provide more information. A previous study revealed that the urine albumin-to-creatinine ratio also demonstrated a negative correlation to GS(31), a finding that also provided a different hypothesis for further investigations on the relationship between sarcopenia and renal protein loss.

Aging is the core basis of sarcopenia(7)and GS has been shown to decline with normal aging(32).In our final model, we included age combined with serum albumin, serum BUN, and UPCR (urine creatinine for the women)as variables to explain GS in the two sexes. The total variance of this model could explain 22.1% of the GS in men and 13.8% of the GS in women. The ability of the current model to predict GS is still low, and we will try to include more appreciative variables to improve the model in future studies.

The key for preventing frailty: nutrient intake and improve renal function

Conclusion

Our study revealed a significant correlation between serum albumin levels and GS in an elderly Taiwanese population. The predictive model, which included age, serum albumin, serum BUN, and UPCR(for men; urine creatinine for women)explained 14%-22% of GS. This result indicates the importance of proper dietary nutritional intake and the preservation of renal function as key issues in preventing frailty among elderly Taiwanese.

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