Frequent hemodialysis: a way to improve physical function?

Whether using quantified tests to assess physical capabilities, or via validated questionnaires, physical function is notably reduced in chronic hemodialysis patients (1). Physical function is a major component of quality-of-life assessment in this population (2) and is best defined as an individual’s ability to perform activities in their daily lives (ADLs) (3). Notably, both poor physical performance and low self-reported physical function scores are predictive of future hospitalization and mortality in chronic hemodialysis patients (4–7). Increased solute removal during hemodialysis has been proposed as a mechanism to reduce mortality, as Kt/urea (the product of the urea clearance and the duration of the dialysis session normalized to the volume of distribution of urea) correlates directly with survival (8). The Hemodialysis (HEMO) study examined the effects of more intense hemodialysis sessions on mortality. Although the intervention failed to demonstrate a survival benefit (9), self-reported physical function was modestly improved (10). In the Frequent Hemodialysis Network (FHN) trial, frequency of hemodialysis was increased (to six times per week) to boost solute removal, again hypothesizing that mortality may be reduced (8). As secondary outcomes, the FHN trial assessed the effect of frequent hemodialysis on physical performance, health, and functioning. The results are presented in this issue of CJASN by Hall et al. (11). Hall and colleagues demonstrated that, compared with conventional hemodialysis, frequent daily hemodialysis improved thephysical health composite (PHC) score, ameasure of self-reported physical function. The physical functioning (PF) subscale, also a measure of self-reported physical function but without the inclusion of ratings for general health, bodily pain, and readiness for everyday physical activities, trended toward improvement as well (although the magnitude of change was large, it failed to reach statistical significance). In contrast, the short physical performance battery (SPPB) score, which quantitatively evaluates the ability to perform basic physical activities, was unchanged. Unlike frequent daily hemodialysis, frequent nocturnal hemodialysis did not improve any of these outcomes, although conclusions may be limited by the smaller sample size in this trial as a result of difficult recruitment. Whereas the SPPB score did not significantly improve with frequent daily hemodialysis, the increased PHC score is of both statistical and clinical significance. Although the improvement in the PF subscale did not achieve statistical significance, the degree of improvement may also likely be clinically meaningful. Measures of self-reported physical function are well validated metrics and significant predictors of mortality and duration of hospitalization (4,12). Of note, there are important limitations to the assessment of physical performance, particularly in chronic hemodialysis patients. Tests of physical performance do not effectively assess ADLs, a major contributor to overall quality of life in this population, and are prone to ceiling effects, thus they may not detect changes in response to an intervention as effectively as self-reported physical function (13). In fact, it is not uncommon for studies to demonstrate differing results from self-reported versus functionally measured physical performance, because these tests are designed to assess different abilities (e.g., ADLs) (13). Thus, the lack of change in the SPPB score does not detract from the importance of the improvement in self-reported physical function (the PHC score and tendency to improve the PF score). In the FHN trial, the degree of improvement in both the PHC score and the PF subscale compared with conventional dialysis was greater than in the HEMO study of increased intensity of hemodialysis sessions. Even after adjustment, both metrics were improved by .3.0 points in the FHN trial, which the authors prespecified as clinically meaningful. This would suggest that the degree of improvement may translate to a reduction in subsequent morbidity and disability. This is consistentwith the significant reduction in the primary outcome ofmortality in the FHN trial (1). Although the present study cannot determine whether the improvement in self-reported physical function contributed to a reduction in mortality, it has been previously suggested that for every 5-point increase in thePHCscore, there is a 10% increase in the probability of survival (14). The negative findings in the nocturnal FHN trial should be interpreted cautiously because of the smaller sample size compared with the daily trial. Given that solute clearance is evengreaterwith frequent nocturnal versus daily hemodialysis (15), the benefits of frequent daily dialysis may also hold true for nocturnal hemodialysis, but may have been missed due to a lack of power. An additional limitation of this study, as noted by the authors, is that the benefits associated with frequent Division of Renal Diseases and Hypertension, University of Colorado Denver Anschutz Medical Center, Aurora, Colorado