Abstract

The objective of this article is to determine the relationship between frailty and socio-demographic/clinical characteristics in patients with chronic kidney disease on dialysis. A cross-sectional study was conducted with 107 participants. Descriptive, correlation and logistic regression analyses were performed, with the level of significance set to 5% (p < 0.05). The prevalence of frailty was 47.66%. Frailty was negatively correlated with cognition (r = -0.30; p = 0.002), functioning on instrumental activities of daily living (r = -0.41; p = 0.000) and hematocrit level (r = -0.19; p = 0.04). The proportion of frailty increased with the age of the participants (OR = 1.03; 95%CI: 1.004-1.069; p = 0.02). Individuals with chronic kidney disease on dialysis had high percentages of frailty, which was associated with an older age and correlated with cognition, functioning on instrumental activities of daily living and a lower hemotocrit level.

Key words
Adult Health; Health of the Elderly; Frailty; Chronic Kidney Failure; Dialysis

Introduction

Chronic diseases require interventions and a change in lifestyle in a continual care process that does not always lead to a cure. Such diseases constitute a considerable public health problem and correspond to 72% of the causes of death¹1 Brasil. Ministério da Saúde (MS). Diretrizes para o cuidado das pessoas com doenças crônicas nas redes de atenção à saúde e nas linhas de cuidado prioritárias. Brasília: MS; 2013.. One such condition is chronic kidney disease (CKD), which is a serious health problem that is considered a growing “epidemic”²2 Siveiro PCL, Machado PJ, Rodrigues PN. Doença renal crônica: um agravo de proporções crescentes na população brasileira. Belo Horizonte:CEDEPLAR/UFMG; 2013..

CKD is defined as an abnormality is renal structure and/or function for more than three months, with implications for one’s health. It is necessary to clarify the cause of the disease and define its stage to identify the risk of negative outcomes, such as kidney failure and death³3 Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int 2013; 3(Supl. 1)1-163..

Patients on dialysis for CKD undergo severe changes in their social life, work, eating habits and sexual life, which can exert a negative impact on both physical and emotional wellbeing. CKD imposes limitations that can distance patients from their social groups, leisure activities and even their families. These factors can make the patient frail, leading to a reduction in quality of life⁴4 Oliveira SG, Marques IR. Sentimentos do paciente portador de doença renal crônica sobre a autoimagem. Rev Enferm UNISA 2011; 12(1):38-42..

Frailty syndrome has a multidimensional nature and is characterized by vulnerability to stressors, with reductions in strength, endurance and physiological functions. This condition increases the risk of adverse events, such as dependence, hospitalization, institutionalization and death⁵5 Morley JE, Vellas B, Van Kan GA, Anker SD, Bauer JM, Bernabei R, Cesari M, Chumlea WC, Doehner W, Evans J, Fried LP, Guralnik JM, Katz PR, Malmstrom TK, McCarter RJ, Robledo LMG, Rockwood K, Von Haehling S, Vandewoude MF, Walston J. Frailty consensus: a call to action. J Am Med Dir Assoc 2013; 14(6):392-397.^,66 Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targenting and care. J Gerontol A Biol Sci Med Sci 2004; 59(3):255-263..

CKD increases the chances of frailty in comparison to individuals with normal kidney function and those with other chronic diseases, such as diabetes, chronic obstructive pulmonary disease, cancer and rheumatoid arthritis⁷7 Mansur HN, Damasceno VO, Bastos MG. Prevalência da fragilidade entre os pacientes com doença renal crônica em tratamento conservador e em diálise. J Bras Nefrol 2012; 34(2):153-160.. Patients with CKD experience reductions in quality of life, cognition, physical activity and muscle mass, with highly prevalent symptoms, such as fatigue, nausea and anorexia⁸8 Johansen KL, Chertow GM, Jin C, Kutner NG. Significance of frailty among dialysis patients. J Am Soc Nephrol 2007; 18(11):2960-2967..

The prevalence of frailty increases as the glomerular filtration rate (GFR) diminishes. Indeed, 14% of patients with CKD are frail, whereas 10% of community-dwelling elderly individuals have the frailty phenotype⁹9 Johansen KL, Delgado C, Bao Y, Kurella Tamura M. Frailty and dialysis initiation. Semin Dial 2013; 26(6):690-696.. The prevalence among patients who begin dialysis is high and frailty is an important construct in this dimension, as it is strongly associated with adverse outcomes¹⁰10 Walker SR, Gill K, Macdonald K, Komenda P, Rigatto C, Sood MM, Bohm CJ, Storsley LJ, Tangri N. Association of frailty and physical function in patients with non-dialysis CKD: a systematic review. BMC Nephrology 2013; 14:228..

The identification of frailty and associated risk factors in patients with CKD on dialysis enables improving care in the public and private health systems to establish more concrete, viable interventions. The present study is justified by the importance of investigating this issue in Brazil, as strategies directed at the control of frailty syndrome can enable better health for the elderly.

It is important to conduct studies that identify patients with CKD on dialysis in situations of pre-frailty and frailty as well as associations with socio-demographic and clinical characteristics, considering the high prevalence of the syndrome in this population. Therefore, the aim of the present study was to determine associations between frailty and both socio-demographic and clinical characteristics in patients with chronic kidney disease on dialysis.

Methods

An observational, descriptive, quantitative, cross-sectional study was conducted involving patients with CKD at a dialysis service in the state of São Paulo (southeastern Brazil).

A non-probabilistic convenience sample was used, totaling 107 participants. Data collection took place between September and November 2014. The inclusion criteria were age 18 years or older, a medical diagnosis of CKD and being on dialysis for at least six months. Individuals with manifestations stemming from a stroke and those with severe vision or hearing impairment were excluded from the study. The data were collected prior to dialysis in a private room at the clinic in an evaluation lasting an average of one hour, during which we administered a questionnaire for the characterization of the participant, the Fried Frailty Phenotype criteria, Addenbrooke’s Cognitive Examination – Revised (ACE-R) and the Lawton Scale.

Socio-demographic and clinical characteristics of the participants were collected using a questionnaire developed by our research group, which has been used in previous studies. This questionnaire addresses socio-demographic and economic characteristics (sex, age, self-declared skin color, schooling and family income) and clinical data (time on dialysis and hematocrit level).

Cognition was assessed using the ACE-R, which is a battery that can be administered to adults and seniors with high sensitivity and specificity for the determination of mild dementia. It is particularly useful for differentiating Alzheimer’s disease from frontotemporal dementia. The ACE-R addresses five domains: orientation/attention (18 points), memory (26 points), verbal fluency (14 points), language (26 points) and visuospatial skills (16 points), which can be evaluated individually. The total score ranges from 0 to 100 points. The cutoff points for the total and domain scores (including the Mini Mental State Examination [MMSE], which was added to the ACE-R) were < 78 for the complete battery, < 17 points for orientation/attention, < 15 points for memory, < 8 points for verbal fluency, < 22 points for language, < 13 points for visuospatial skills and < 25 points for the MMSE¹¹11 Carvalho VA, Barbosa MT, Caramelli P. Brazilian version of Addenbrooke's Cognitive Examination in the diagnosis of mild Alzheimer Disease. Cog Behav Neurol 2010; 23(1):8-13..

Instrumental activities of daily living were evaluated using the Lawtwon Scale, which is employed to determine the functional performance of adults and seniors in terms of instrumental activities that enable maintaining an independent life, such as using the telephone, shopping, preparing meals, housekeeping, doing manual domestic chores, managing medications and managing finances. The score ranges from 7 (complete dependence) to 21 points (complete independence). Scores higher than seven and lower than 21 indicate partial dependence¹²12 Lawton MP, Brody E. Assessment of older people: self-maintaining and instrumental activities of daily living. The Gerontologist 1969; 9(3):179-186..

Frailty syndrome was investigated using the five items described as the components of the frailty phenotype⁶6 Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targenting and care. J Gerontol A Biol Sci Med Sci 2004; 59(3):255-263.:

a) self-reported unintentional weight loss in the previous year (> 4.5 kg or > 5% of habitual weight);

b) sensation of exhaustion, evaluated using the following two questions: “How often in the past week have you felt that everything you did required considerable effort?” and “How often in the past week did you feel that you could not get going?” Answers of “most of the time” or “always” on at least one of these questions fulfilled this criterion of frailty;

c) weakness, evaluated based on grip strength measured using a manual dynamometer (Grip model, SAEHAN®) with the upper limb in which there is no arteriovenous fistula. The participants were instructed to exert maximum force on three trials. Those in the first quintile after adjusting for sex and body mass index were considered as having fulfilled this criterion of frailty;

d) slow gait speed, evaluated using a chronometer to measure the time (in seconds) required to travel a 4.6-m track. The mean of three consecutive trials was used, with adjustments made for sex and height;

e) low physical activity, self-reported based on the answer to the following question: “Do you think that you perform fewer physical activities than you did 12 months age?” An affirmative answer was considered as having fulfilled this frailty criterion.

Having three or more frailty criteria denoted frailty, fulfilling one or two criteria denoted pre-frailty and not fulfilling any of the criteria denoted non-frailty⁶6 Fried LP, Ferrucci L, Darer J, Williamson JD, Anderson G. Untangling the concepts of disability, frailty, and comorbidity: implications for improved targenting and care. J Gerontol A Biol Sci Med Sci 2004; 59(3):255-263..

The data analysis involved descriptive statistics (measures of central tendency [mean, median, minimum and maximum] and dispersion [standard deviation]). Spearman’s correlation coefficients were calculated to determine the strength of the correlations between the frailty phenotype score and both socio-demographic and clinical variables. The coefficients were interpreted as follows¹³13 Levin J, Fox JA, Forde DR. Estatística para ciências humanas. 11ª ed. São Paulo: Pearson; 2012.: < 0.3) = weak correlation, 0.3 to 0.59 = moderate correlation, 0.6 to 0.9 = strong correlation and 1.0 = perfect correlation. Logistic regression analysis was used to determine the effect of socio-demographic and clinical variables on frailty. The level of significance for the statistical tests was α = 0.05 (p ≤ 0.05).

This study received approval from the Human Research Ethics Committee of the Federal University of Carlos (UFSCar).

Results

Among the 107 interviewees, the majority was male (67.30%). Schooling ranged from 0 to 20 years (mean: 7.26 years). Mean time on dialysis was 48.91 (46.81) months (Table 1).

The prevalence of frailty, pre-frailty and non-frailty was 47.66% (n = 51), 44.85% (n = 48) and 7.49% (n = 8), respectively.

The participants with the highest degree of frailty had a poorer performance on the cognitive assessment (r= -0.30; p = 0.002), poorer functioning on instrumental activities of daily living (r = -0.41; p = 0.000) and a lower hematocrit level (r = -0.19; p = 0.04) (Table 2).

Older patients were at greater risk of being frail. Each year of life increased the chance of frailty by 3%. None of the other variables studied were significantly associated with the risk of frailty (Table 3).

Skin color, income per capita, time on dialysis, age and cognition (ACE-R) were associated with frailty in the bivariate analysis (p ≤ 0.20) and incorporated into the multivariate model. Using the stepwise backward method, independent variables with p > 0.05 were excluded from the final model, leaving only age.

Discussion

The term frailty has been employed to distinguish weaker, more vulnerable individuals. Recent national and international studies have contributed to a better definition of the clinical and physiological properties of frailty, highlighting the vulnerability of frail elderly individuals and the negative outcomes of this condition⁷7 Mansur HN, Damasceno VO, Bastos MG. Prevalência da fragilidade entre os pacientes com doença renal crônica em tratamento conservador e em diálise. J Bras Nefrol 2012; 34(2):153-160.

8 Johansen KL, Chertow GM, Jin C, Kutner NG. Significance of frailty among dialysis patients. J Am Soc Nephrol 2007; 18(11):2960-2967.

9 Johansen KL, Delgado C, Bao Y, Kurella Tamura M. Frailty and dialysis initiation. Semin Dial 2013; 26(6):690-696.

10 Walker SR, Gill K, Macdonald K, Komenda P, Rigatto C, Sood MM, Bohm CJ, Storsley LJ, Tangri N. Association of frailty and physical function in patients with non-dialysis CKD: a systematic review. BMC Nephrology 2013; 14:228.

11 Carvalho VA, Barbosa MT, Caramelli P. Brazilian version of Addenbrooke's Cognitive Examination in the diagnosis of mild Alzheimer Disease. Cog Behav Neurol 2010; 23(1):8-13.

12 Lawton MP, Brody E. Assessment of older people: self-maintaining and instrumental activities of daily living. The Gerontologist 1969; 9(3):179-186.

13 Levin J, Fox JA, Forde DR. Estatística para ciências humanas. 11ª ed. São Paulo: Pearson; 2012.^-1414 Kim JC, Kalantar-Zadeh K, Kopple JD. Frailty and protein-energy wasting in elderly patients with end stage kidney disease. J Am Soc Nephrol 2013; 24(3):337-351..

Although patients with CKD on dialysis at times have clinical signs and symptoms compatible with frailty, there is little information on the socio-demographic and clinical factors that may be associated with the condition in this population¹⁵15 Kutner NG, Zhang RMS, Huang Y, McClellan WM, Soltow QA, Lea J. Risk factors for frailty in a large prevalent cohort of hemodialysis patients. Am J Med Sci 2014; 348(4):277-282..

The identification of frailty and its predictors in the dialysis setting can potentially lead to the identification of patients at risk of adverse outcomes and who could benefit from interventions directed at preventing their decline⁸8 Johansen KL, Chertow GM, Jin C, Kutner NG. Significance of frailty among dialysis patients. J Am Soc Nephrol 2007; 18(11):2960-2967..

In the present study, a large portion of patients with CKD on dialysis were frail and frailty syndrome was related to cognitive impairment, functional deficit, a lower hematocrit level and a more advanced age.

These findings are in agreement with data described in national and international studies, which report that frailty is more prevalent in this population⁷7 Mansur HN, Damasceno VO, Bastos MG. Prevalência da fragilidade entre os pacientes com doença renal crônica em tratamento conservador e em diálise. J Bras Nefrol 2012; 34(2):153-160.^,1616 Willhelm-Lenn ER, Hall YN, Tamura MK, Chertow GM. Frailty and chronic kidney disease: the Third National Health and Nutrition Evaluation Survey. Am J Med 2009; 122(7):664-671.

17 McAdams-Demarco MA, Suresh S, Law A, Salter ML, Gimenez LF, Jaar BG, Walston JD, Segev DL. Frailty and falls among adult patients undergoing chronic hemodialysis: a prospective cohort study. BMC Nephrology 2013; 14:224.

18 Roshanravan B, Kathri M, Robinson-Cohen C, Levin G, Patel KV, De Boer IH, Seliger S, Ruzinski J, Himmelfarb J, Kestenbaum B. A prospective study of frailty in Nephrology-Referred patients with CKD. Am J Kidney Dis 2012; 60(6): 912-921.

19 Bao Y, Dalrymple L, Chertow GM, Kaysen GA, Johansen KL. Frailty, dialysis initiation, and mortality in end-stage renal disease. Arch Intern Med 2012; 172(24):1071-1077.

20 Reese PP, Cappola AR, Shults J, Townsend RR, Gadegbeku CA, Anderson C, Baker JF, Carlow D, Sulik MJ, Lo JC, Go AS, Ky B, Mariani L, Feldman HI, Leonard MB; CRIC Study Investigators. Physical performance and frailty in chronic kidney disease. Am J Nephrol 2013; 38(4):307-315.

21 Mansur HN, Colugnati FAB, Grincenkov FRS, Bastos MG. Frailty and quality of life: a cross-sectional study of Brazilian patients with pre-dialysis chronic kidney disease. Health Qual Life Outcomes 2014; 12:27.^-2222 Johansen KL, Dalrympe LS, Delgado C, Kaysen GA, Kornak G, Grimes B, Chertow GM. Association between body composition and frailty among prevalent hemodialysis patients: A US Renal Data System Special Study. J Am Soc Nephrol 2014; 25(2):381-389.. Associated factors identified by other authors include peripheral vascular disease, heart disease, the black race and a lower concentration of serum albumin¹⁵15 Kutner NG, Zhang RMS, Huang Y, McClellan WM, Soltow QA, Lea J. Risk factors for frailty in a large prevalent cohort of hemodialysis patients. Am J Med Sci 2014; 348(4):277-282.; mortality and hospitalization⁸8 Johansen KL, Chertow GM, Jin C, Kutner NG. Significance of frailty among dialysis patients. J Am Soc Nephrol 2007; 18(11):2960-2967.; number of hospitalizations and the risk of falls¹⁷17 McAdams-Demarco MA, Suresh S, Law A, Salter ML, Gimenez LF, Jaar BG, Walston JD, Segev DL. Frailty and falls among adult patients undergoing chronic hemodialysis: a prospective cohort study. BMC Nephrology 2013; 14:224.; diabetes mellitus¹⁸18 Roshanravan B, Kathri M, Robinson-Cohen C, Levin G, Patel KV, De Boer IH, Seliger S, Ruzinski J, Himmelfarb J, Kestenbaum B. A prospective study of frailty in Nephrology-Referred patients with CKD. Am J Kidney Dis 2012; 60(6): 912-921.; a high GFR¹⁹19 Bao Y, Dalrymple L, Chertow GM, Kaysen GA, Johansen KL. Frailty, dialysis initiation, and mortality in end-stage renal disease. Arch Intern Med 2012; 172(24):1071-1077.; the use of vitamin D and parathyroid hormone⁷7 Mansur HN, Damasceno VO, Bastos MG. Prevalência da fragilidade entre os pacientes com doença renal crônica em tratamento conservador e em diálise. J Bras Nefrol 2012; 34(2):153-160.; low physical performance and CKD severity²⁰20 Reese PP, Cappola AR, Shults J, Townsend RR, Gadegbeku CA, Anderson C, Baker JF, Carlow D, Sulik MJ, Lo JC, Go AS, Ky B, Mariani L, Feldman HI, Leonard MB; CRIC Study Investigators. Physical performance and frailty in chronic kidney disease. Am J Nephrol 2013; 38(4):307-315.; poorer quality of life, sex and age²¹21 Mansur HN, Colugnati FAB, Grincenkov FRS, Bastos MG. Frailty and quality of life: a cross-sectional study of Brazilian patients with pre-dialysis chronic kidney disease. Health Qual Life Outcomes 2014; 12:27..

However, the prevalence of frailty in the present investigation was higher than that reported in surveys of community-dwelling individuals, suggesting an increased health risk in this population, which has implications for health services and could lead to excessive burden on the part of health professionals at dialysis centers.

The limitation of the present study regards the cross-sectional design, which does not enable the determination of the cause-and-effect relationship. Thus, longitudinal investigations in this setting are needed for a greater understanding of the genesis of this syndrome in patients with CKD.

The identification of health status related to pre-frailty can favor the planning and implementation of care for adults and seniors in this context.

Considering the scarcity of Brazilian studies on this issue, the present findings broaden knowledge on the socio-demographic and clinical factors associated with frailty in the nephrology setting.

Thus, these findings can assist in the establishment of preventive health actions aimed at delaying the emergence and progression of frailty. There is a need for reflection on the healthcare system in terms of addressing the needs of adults and seniors with CKD in light of the negative impact of frailty syndrome on this population.

Conclusion

The prevalence of frailty was high among individuals with chronic kidney disease on dialysis. Moreover, frailty was negatively correlated with cognition, functioning on instrumental activities of daily living and hemotocrit level. This condition was also associated with a more advanced age.

Acknowledgments

This study received funding from the Brazilian fostering agency Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

References

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