Senescence or Frailty? Are Chronic Disease Patients Different?

Chronic kidney disease (CKD) has long been known to negatively affect an individual’s quality of life. Identifying potentially modifiable risk factors may assist the physician in blunting, or even reversing this effect. In a recent article published in the American Journal of Kidney Diseases, Roshanravan  and colleagues make  strides to standardize the assessment of the frailty phenotype. A goal of the authors’ work is to guide risk stratification for this population and provide an opportunity for the clinician to intervene. Dr Baback Roshanravan, corresponding author from the University of Washington Kidney Research Institute, Seattle, WA, discusses this recent article with Dr Kellie Calderon (eAJKD), eAJKD Advisory Board member.

eAJKD: What interested you to start studying this topic?

BR: My interest began from my clinical work in the nephrology clinic at Harbor View Medical Center. In that population, I noticed people with CKD were affected differently by their illness and had a high burden of cardiovascular disease. Previously, the Cardiovascular Health Study (CHS) described the frailty phenotype in an older population (mean age around 76). I noticed that a lot of our referral population for CKD seemed to be functioning at the level of an elderly individual. However, they’re not frail in the same respect as the 76-year-old, thin individual. On average, they are more overweight and less capable of physical activity than the individuals in the cardiovascular health studies. It was interesting to take that paradigm of frailty and apply it to a younger population, and see if the associations that were discovered in the older adult population with death all caused mortality also apply to younger patients with CKD. Hence, I decided to look at this area, apply this paradigm to the CKD population, and assess what impact it has on outcomes of death or dialysis.

eAJKDFor most people, “frailty” invokes the image of a thin, elderly individual which is in contrast to the frailty phenotype that is described in this study. Please describe how frailty is quantified and standardized.

BR: The scoring system is similar to the one developed for the CHS and looks at major components of frailty. These include weight loss, weakness by grip strength, physical activity assessed by exercise, slowness by gait speed, and exhaustion. We used the same cut-offs as in the CHS, with the presumption that CKD is a model for premature aging.

eAJKD: This study found that despite our notions of frailty, the African American population is actually more likely to be frail and obese. USRDS reports that this population actually has a survival advantage on dialysis. How do you reconcile this?

BR: Our data shows that even after accounting for race, sex, age, GFR (by cystatin C), body mass index, diabetes, and prevalent cardiovascular disease, the frailty phenotype is associated with 2.2 fold greater risk of death or dialysis. The frailty phenotype even applies to African Americans, and African Americans are more likely to be frail than non–African Americans.

eAJKDPlease comment on the decision to use cystatin C as part of your GFR estimation.

BR: We chose cystatin C for this study because sarcopenia, or decreased muscle mass or function, is associated with several components of frailty. Grip strength and gait speed, to some extent, are associated with muscle mass. The use of cystatin C rather than creatinine was intended to avoid potential confounding of those variables.

eAJKD: What would you like clinicians to take away from this work?

BR: Several components of frailty can be improved by increasing activity and exercise. In particular, resistance exercise can improve gait speed and several other performance measures. Small Studies in the CKD population suggest that exercise, either aerobic or resistance, can improve physical performance measures.

The next step is to look at different physical performance measures in CKD patients and their association with all-cause mortality, which we are working on now. It is important in the overall physician-patient relationship to evaluate the burden of CKD. Even when accounting for co-morbidities, there are people who have some sub-clinical disease burden that may impact on multiple domains of their well-being.

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