Jennifer Bergeron (@DrJennyBee) is an Assistant Professor of Medicine and the Assistant Nephrology Program Director at West Virginia University. She completed her residency at the University of Vermont and her fellowship at Vanderbilt University, though will always be a Mainer. Her clinical and research interests include palliative nephrology and CKD care, sharing her love of renal physiology, and mentorship.

In shared decision making with patients who have advanced chronic kidney disease, patients and their families often ask what their life will look like if they choose to pursue dialysis. Will they feel better or worse than they do now? Will they be able to maintain their independence? In fact, nearly half of patients with advanced CKD ranked maintaining independence as their top health outcome priority and it is a top three priority for patients on dialysis. These questions can be difficult to answer, especially as the dialysis landscape has changed over the last 60 years. Across the globe, patients are living on dialysis longer (as seen in Japan, the US, and Taiwan) and some patients have been on dialysis for 50 years!

One way to answer these questions about patients’ function is by assessing and discussing frailty. Frailty is challenging to define and measure. Frailty is a clinical syndrome characterized by increased vulnerability to adverse health outcomes and decreasing physical, cognitive, and functional abilities over time. Unfortunately, over one-third of patients on dialysis are frail (range 6-82%). Although frailty is associated with increasing age and comorbidities, we don’t know if dialysis itself is associated with frailty. Yamamoto et al set out to answer this question in their new study “Frailty and Duration of Maintenance Dialysis: A Japanese Nationwide Cross-Sectional Study”.

Using the Japanese Society for Dialysis Therapy Renal Data Registry, 227,136 patients who were over 50 years old and on dialysis in 2018 were identified. They were divided into groups based on dialysis vintage, or how many years they had been on dialysis: <5 years (reference group), 5-<10 years, 10-<20 years, 20-<30 years, and >30 years. The outcomes of frailty and bedridden status were measured. Frailty was defined as a grade 2-4 and bedridden as grade 4 on the Eastern Cooperative Oncology Group Performance Status Scale (ECOG PS).

In the study population, 5,510 patients (2.4%) had a dialysis vintage of 30 years or more. The prevalence of frailty and bedridden status in this group was 36.2% and 6.4%, respectively. Frailty significantly increased with dialysis vintage: compared with patients on dialysis <5 years, the adjusted prevalence ratio (aPR) of frailty was 1.06 in 5-10 years dialysis vintage, 1.10 in 10-20 years, 1.14 in 20-30 years, and 1.67 in >30 years. Compared with <5 years dialysis vintage, all groups showed a higher prevalence of being bedridden, with the highest aPR (1.66) in patients with >30 years dialysis vintage. Even when adjusted for a plethora of covariates in four separate models, the prevalence of frailty and bedridden status was highest in the group on dialysis for over 30 years.

When reviewing the results, we might wonder if the increased frailty seen in higher dialysis vintages comes not from the dialysis, but by the patient’s age- are the patients who have been on dialysis longer, simply older? No, the patients in this study with dialysis vintage >30 years were younger! Their median age was 67 years old compared to 71 years in the total study cohort and 73 years in the <5 years group. Patients on dialysis the longest also had a younger age of dialysis initiation (32 years old vs 71 years old in the <5 years group).

There were several other differences in the patients with the longest dialysis vintage. They were more likely to be women, have worse nutritional indices, have chronic glomerulonephritis as their cause of kidney disease, have a decreased prevalence of diabetes, cardiovascular complications, and dementia, and have a higher prevalence of dialysis-related amyloidosis. Part of these findings can be attributed to survival and selection bias, as the patients with long dialysis vintage had to be healthy enough to survive for years, but perhaps not healthy enough to receive a transplant.  Patients with dialysis vintage >30 years were also less likely to have arteriovenous fistulas, likely from experiencing multiple vascular access failures. In fact, previous work showed that long-term dialysis patients were more likely to die from infection than cardiovascular disease. Could this observation be driven by line and graft infections? As the authors point out, these factors should be the focus of future research.

The major strength of this study is the size of the cohort. A previous meta-analysis on this topic showed no association between dialysis and frailty, but the studies were significantly smaller, with the median being 379 patients (range 51 – 1,250) in comparison to this study’s roughly 230,000 patients. Of note, the meta-analysis statistics were also based on meta-regression and not on duration of dialysis alone, which may have masked the association. Another strength of Yamamoto et al’s study was capturing such long dialysis vintage. Frailty has been previously associated with dialysis duration before transplantation, but the dialysis vintage only went up to 6 years (and only had 205 patients).

One limitation, as with any cross-sectional study, is that a causal relationship between dialysis vintage and frailty or bedridden status could not be established. However, the authors adjusted for important confounding and intermediate factors (age, sex, nutritional status, factors related to physical function, cardiovascular comorbidities, dementia, and vascular access type) and still demonstrated the strength of the association.

Another limitation inherent in any frailty study is the measurement of frailty itself. There are innumerable frailty assessment tools and it is unclear which is “best”. These tools can be divided into “phenotypic frailty” models which measure physical function or “cumulative deficits” models which assess various domains of disability, disease, physical, cognitive, and psychological function (Figure 1).  The ECOG PS used in this study is a phenotypic frailty model so it does not capture the psychosocial domains, and is not as well validated as the Fried phenotype. However, the more robust a tool, the more difficult it is to use in large studies. Despite the ECOG PS limitations, having a frailty assessment on 230,000 patients is commendable.

Figure 1. Frailty Assessment Tools, © Bergeron.

Yamamoto et al’s study shows the association of dialysis and frailty, which is important information to share with patients and their families. Even patients with 5 years of dialysis experienced higher rates of frailty and bedridden status that only increased with time on dialysis. Awareness of this decline in physical function during maintenance dialysis may help patients and their families better plan their lives around what is truly important to them.