Sarcopenia And Chronic Kidney Disease
Overview
Sarcopenia and frailty are common conditions among people with chronic kidney disease (CKD), which may further enhance their risk of developing adverse health complications. Only a few studies have demonstrated the association between sarcopenia, frailty and chronic kidney disease in patients who are not on dialysis. This study is targeted at studying and assessing the relationship between frailty-associated factors and chronic kidney disease stage I-IV among elderly patients.
774 elderly patients with chronic kidney disease stage I-IV were enrolled into the study from 29 different medical centers between 2017 March to 2019 September. The Frailty Index (FI) was established to assess the risk of frailty and the distribution of the frailty index among the elderly CKD patients recruited for this study. The definition given by the Asian Working Group for Sarcopenia in 2019 was used to define sarcopenia in this study population. The factors associated with the condition of frailty were assessed using multinomial logistic regression analysis.
774 elderly CKD patients with a median age of 67 years consisting mainly of males (66%) were a part of the study. The enrolled patients had an estimated median GFR of 52.8mL/min/1.73 m2. The overall sarcopenia prevalence among the study group was 30.6%. The frailty index distribution showed right-skewing. The frailty index age-related slope on a logarithmic scale was 1.4% per annum. Frailty index was observed to be linked to mortality. Advancing age, sarcopenia, chronic kidney disease stages II-IV, high waist to hip ratio and low serum albumin levels were noted to have a significant correlation with a high frailty index on a multinomial multivariate logistic regression analysis. Also, chronic kidney disease stages III-IV and advancing age were seen to have a significant association with a median frailty index.
A higher frailty risk in elderly patients with chronic kidney disease stages I-IV was seen to be independently associated with sarcopenia. It is thus advised that frailty should be evaluated in patients who are advanced in age with sarcopenia, high stage chronic kidney disease, low levels of serum albumin and high waist to hip ratio.
Introduction
Frailty
Frailty is a clinical condition that is related to age. It is described by a reduction in the physiological reserve of various organ systems. Here, there is lesser ability to adapt to environmental stimuli and stressors like physical trauma or presence of acute disease or illness. Frailty causes derangements in several organ systems simultaneously, i.e. the presence and severity of frailty cannot be evaluated using just one diagnostic biomarker or investigation.
Currently, the Rockwood Frailty Index and the Fried Frailty Phenotype are the most commonly utilized models to apply the frailty concept. Fried developed the Frailty phenotype where a minimum of three criteria had to be present which include: weakness, exhaustion which is self-reported, reduced physical activity, slower walking speed and unintentional weight loss.
Rockwood described the Frailty Index as the amount of accumulated deficiencies (functional impairments, derangements in laboratory results, signs and symptoms). This Frailty Index led to a multidimensional and detailed evaluation of frailty and the degrees or severity of frailty.
Sarcopenia
Sarcopenia is a condition that is described as a generalized and progressive loss of strength and mass of skeletal muscles. This condition may lead to an increased risk of adverse health complications like poor quality of life, physical disabilities and even death. It is important to note that muscle mass varies among people of different ethnic groups. Older studies reported that Asians are more likely to have lower body mass index, lower muscle strength, lower skeletal muscle mass and lower body fat than other groups. This should be accounted for when making a diagnosis of sarcopenia in people of different ethnic groups.
In physiological states, the rate at which new muscle cells develop, undergo hypertrophy and lose proteins is maintained in a homeostatic balance. This homeostatic balance is regulated by the endocrine system, the nervous system and the immune system. This balance may also be affected by a person’s level of physical activity and nutritional status. Frailty characterized by an unregulated and overactive immune inflammatory response can lead to increases in the rate of muscle cell decomposition causing a decline in muscle strength and quality with a resultant drop in function of the affected muscle.
Chronic Kidney Disease
CKD has been seen to be a public health issue worldwide. Its prevalence is 11-16% among the general population. The prevalence of chronic kidney disease among the elderly is on the increase due to the fact that elderly people are more vulnerable to chronic conditions like hypertension, diabetes, cardiovascular disease and other diseases which will necessitate chronic use of medications or need for surgical interventions. Frailty, malnutrition, osteoporosis and declines in cognitive and physical functions are common among elderly patients who have chronic kidney disease. Elderly patients who have chronic kidney disease are also more likely to have cardiovascular complications or die rather than develop end stage renal disease when compared to younger patients with chronic kidney disease. Studies have shown that the occurrence of frailty among elderly patients with chronic kidney disease is prevalent among those who are on dialysis and those who are not. The risk of occurrence of adverse health complications such as falls, disabilities, hospitalizations and even deaths are seen to be increased by frailty and sarcopenia.
In patients with CKD, their body composition begins to change as the disease progresses. Protein catabolism which causes a decline in muscle strength and mass is due to the reduction in kidney metabolism observed as chronic kidney disease progresses which activates the pathways surmounting to metabolic acidosis, chronic inflammatory response, buildup of uremic toxins, endocrine derangements and anorexia. Fatigue following dialysis and activity restriction during dialysis reduces the amount of physical activity carried out which may further affect muscle functionality. Also, dialysis modalities such as peritoneal dialysis and hemodialysis enhance the degradation of proteins, decrease synthesis of proteins and this effect continues to persist after dialysis eventually causing a decrease in muscle mass. It is vital that patients with chronic kidney disease are also evaluated for frailty and sarcopenia alongside other possible co-morbidities. Several studies carried out in the past on frailty used the Fried Frailty Phenotype to describe frailty, and this focuses more on physical frailty. Only a few studies on frailty described frailty using the Frailty Index which focuses on both psychosocial and physical frailty. Here, a Chinese prospective observational study of elderly people who had chronic kidney disease was carried out. Data was obtained on the baseline data which include sarcopenia and Frailty Index. This study is targeted at evaluating the factors related to frailty and demonstrates the correlation between sarcopenia and frailty. This study is expected to help in the early identification of hospitalized CKD patients with frailty comorbidities.
Method
This study was a cross-sectional, multicentered, observational study which analyzed the baseline data of a prospective observational study on the Chinese elderly population with chronic kidney disease. The aim of this study was to assess the presence of frailty among elderly Chinese patients with chronic kidney disease stages I-IV. From 29 medical centers in China, elderly patients aged greater than 60 years, with chronic kidney disease stages I-IV were enrolled into the study. The 29 medical centers from which they were recruited were the renal unit of different hospitals.
The diagnosis of chronic kidney disease was made using a previous history of chronic kidney disease lasting longer than 3 months; decreased estimated GFR less than 60 mL/min/1.73 m2 or the ratio of albumin to creatinine being greater than 30 mg/g or increased protein levels in urine (proteinuria) greater than 150 mg/day. Estimated glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKDEPI) creatinine equation. The 2012 guidelines for Kidney Disease Improving Global Outcomes (KDIGO) were followed in the staging of chronic kidney disease. The Chinese General Hospital Ethics Committee gave approval for this study, and every patient included in this study gave informed consent.
A deficit accumulation technique was used to construct a means to measure frailty. In the Systolic Blood Pressure Intervention Trial (SPRINT), a Frailty Index consisting of 37 items were modified based on items present in the cohort, which were 30 in number. An addition of 5 more items obtained from the African American Health (AAH) cohort and Hypertension in the Very Elderly Trial (HYVET) cohort was added to the Frailty Index. The Frailty Index was determined by the sum total of every deficit divided by the sum total of items which are not missing.
The handgrip strength test was used to define low muscle strength in sarcopenia. A handgrip strength of < 18 kg for females and < 28 kg for males is indicative. Gait speed test was used to define a decline in physical performance seen in sarcopenia. A gait speed score of < 1 m/s for both males and females is indicative. Appendicular skeletal muscle mass index (ASMI) was used to define low muscle mass seen in sarcopenia. Appendicular skeletal muscle mass index of < 5.7 kg/m2 in females and < 7 kg/m2 in males is indicative. Low muscle mass was also defined using the mid-upper arm circumference as this measurement was seen to be closely related to Appendicular skeletal muscle mass index. Mid-upper arm circumference of ≤ 27.5cm in females and ≤ 28.6 cm in males is indicative.
Inclusion Criteria
Patients who were to be included into the study were above 60 years of age and had been diagnosed with chronic kidney disease stage I-IV.
Exclusion Criteria
Patients who had previously received dialysis or undergone renal transplant were excluded from the study. Other patients who were excluded from the study were those: who were given a diagnosis of AKI, who had metastatic or active tumors in the last 2 years, who had severe cardiac failure as classified by the NYHA as grade III or IV, who are infected with HIV, who have difficulties in communication even with aid from examiners, those who were unable to follow the protocols of the study and who have isolated hematuria. Patients who did not have a minimum of 30 items in the Frailty Index which are non-missing were additionally excluded from the study.
Result
A total of 1051 elderly Chinese patients who had chronic kidney disease were recruited into this study. Of this number, a total of 277 elderly patients were excluded from the study as they did not meet up with the requirements. Consequently, a total number of 774 patients were included as they met the inclusion criteria.193 elderly patients were enlisted at the First Chinese PLA Medical Center for a median duration of 36.5 months.
Of the 774 patients, 584 (75.5%) were hypertensive, 276 (35.7%) were diabetic, 237 (30.6%) were sarcopenic and 123 (15.9%) came down with a stroke. Participants who had the highest Frailty Index had higher serum cystatin C levels, heavier proteinuria, higher waist to hip ratio, higher handgrip strength, higher serum calcium levels and higher serum phosphorus levels. Patients who had lower Frailty Index mostly had stage I chronic kidney disease. Patients with median and higher Frailty Index mostly had stage IV chronic kidney disease.
Chronic kidney disease stage, age, sarcopenia, waist to hip ratio, serum cystatin C levels, proteinuria, albumin levels, phosphorus levels, parathormone levels, white blood cell count and differentials were seen on a univariate logistic regression study to be correlated with a high Frailty Index status. Chronic kidney disease stage, waist to hip ratio, age, serum cystatin C levels, parathormone levels, white blood cell count and differentials were seen on a univariate logistic regression study to be correlated with a median Frailty Index status in elderly patients who have chronic kidney disease. Chronic kidney disease stage II-IV, advancing age, sarcopenia, low albumin levels and increased waist to hip ratio was seen to have a significant correlation with high Frailty Index status on Multivariate logistic regression studies. Chronic kidney disease stage II-IV and advancing age were seen to have a significant correlation with median Frailty Index status on Multivariate logistic regression studies.
There was a notable relationship between serum albumin and sarcopenia.
Conclusion
Frailty and sarcopenia are common occurrences in elderly patients who have CKD even prior to the onset of dialysis. Sarcopenia was seen to be independently linked to a higher risk for developing frailty. Elderly patients who are advanced in age and have a high chronic kidney disease grade, sarcopenia, low albumin levels and proteinuria need to be screened to rule out frailty. Early identification and management of elderly patients at risk for frailty is vital in reducing the rates of health disabilities among elderly patients who have chronic kidney disease.
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