Frailty in Patients on Maintenance Hemodialysis

What is frailty?

The word “frailty” comes from the Latin word “fragilitas,” which means “weakness” or “fragility.” It was first defined in gerontology in the context of aging as characterized by a decline in reserve and function across multiple physiologic systems. The frail individual loses the ability to cope with daily activities or acute stress.² A person with frailty has less energy, muscle mass, and strength, with reduced exercise capacity. Frailty is a function of the physiological age, not just the chronological one. So, not all frail individuals are older, and not all older individuals are frail.

It is essential to consider frailty in the comprehensive evaluation of individuals with chronic diseases. Frailty is associated with future risk of hospitalization, disability, and even death. Frailty in kidney disease occurs due to genetic, psychosocial, behavioral, cellular, and molecular mechanisms secondary to a diverse array of factors, including mitochondrial dysfunction, uremia, acidosis, inflammation, and advanced glycation end products.³ These factors are associated with protein energy wasting, leading to muscle wasting and loss of strength and ultimately sarcopenia.

Studies have reported a higher prevalence of frailty in CKD populations, especially those on dialysis.^4-5 This higher prevalence is due to various pathological factors overlapping between kidney disease and frailty. Evidence has demonstrated that frailty has good predictive validity in assessing risk for morbidity and mortality in kidney disease.

There are only a few Indian studies on frailty in CKD. Joseph et al.⁶ showed the prevalence of frailty to be 43% among 84 patients on hemodialysis, similar to this study (49.4%). However, Yadla et al.⁷ reported a higher prevalence of 81%. The prevalence of frailty in patients with kidney disease varies between 31% to 80% in various studies⁸ and can be attributed to factors, including characteristics of the study population, and the test used to identify the frailty.

The current study showed a high prevalence of frailty in a relatively young cohort, with a median age of approximately 37 years. It is in contrast with the Western studies, where people aged 65 years and above were frail, especially in countries like Japan. It likely reflects the differences in population demographics, the younger onset of CKD in India, delayed diagnosis, and older adults with multiple comorbidities may be less frequently referred for long-term dialysis due to poor social support. Females are at an increased risk of frailty because of lower lean mass and strength.

Multimorbidity is a risk factor for frailty. This study showed a higher prevalence of diabetes mellitus, hypothyroidism, and coronary artery disease in frail patients. Notably, these comorbidities are common in CKD, which acts as a confounding factor and raises the question as to whether frailty is related to uremia or comorbid conditions. The prevalence of diabetes is lower in this study as compared to the previous two Indian studies.

In a country like India, with a high prevalence of malnutrition, the contribution of nutrition-related factors to frailty must be considered. Protein energy wasting in CKD leads to sarcopenia, which contributes to the development of frailty in CKD. Factors such as uremia, metabolic acidosis, anorexia, low testosterone, and vitamin D levels play a major role in the pathogenesis of sarcopenia in CKD.⁸ The predictors of protein energy wasting in CKD are MUAC, albumin, and dialysis malnutrition score.⁹ This study showed that frail patients had lower MUAC, albumin, and cholesterol levels, which indicates malnutrition and protein-energy wasting.

This study has used two scales to measure frailty, FFP and the CFS [Table 1]. The Fried scale defines frailty based on five criteria, and the presence of 3/5 is considered diagnostic. It includes weakness, unintentional weight loss, slow gait, exhaustion, and low activity. CFS is a clinical judgement tool to assess frailty by evaluating specific domains, including comorbidity, function, and cognition, which has seven categories from very fit to severely frail. Most of the studies have used only Fried’s. However, these scales are not validated in the kidney disease population. The frailty index for dialysis and the Frailty index- CKD were developed and validated in the kidney disease population, but using these scales is cumbersome in routine practice, as each has more than 50 variables to assess frailty.

The primary purpose of assessing frailty in kidney disease is to identify its outcomes. Dialysis patients who are frail have poor scores on cognitive screening, frequent falls, frequent hospitalization, depression, poor quality of life, and higher mortality. As this is a cross-sectional study, long-term outcomes of frail patients could not be assessed. We require a longitudinal study with prolonged follow-up to investigate the long-term outcomes of frailty in our CKD population.

There are some trials that focus on the treatment of frailty in CKD with exercise intervention using strength and flexibility training on interdialytic days. None showed any improvement in frailty levels after intervention.¹⁰

Frailty has also been studied in kidney transplant recipients, where it is associated with delayed graft function, longer hospitalization, early re-admission, and immunosuppression intolerance. Interestingly, frailty worsens in the first month following kidney transplantation but then shows a sustained long-term improvement in observational studies.¹¹ It is important to clarify that frailty is not a contraindication for kidney transplantation; rather would help the patient recover.

In conclusion, this study highlights a high burden of frailty in a younger Indian dialysis cohort and points to actionable correlates, nutrition, and hemodynamic stability, that dialysis teams can target while we wait for definitive interventional trials.