Discussion
Frequent hemodialysis has been reported to preserve nutritional status and prevent or attenuate the anticipated decline in BCM, and has been associated with improved appetite, increased protein and caloric intake, and incremental increases in dry weight, muscle mass, and serum albumin in various studies. In contrast to most previous studies, the FHN Daily and Nocturnal Trials were randomized and used monthly measures of serum albumin, ePCR, as well as serial bioimpedance-based measures, rather than anthropometric measures of body composition. The HEMO Trial, a 2 × 2 factorial randomized trial of >1800 subjects dialyzed three times per week at standard and high per session eKt/Vurea and with high and low flux dialyzers, showed a progressive decline in serum albumin, equilibrated normalized protein catabolic rate, and body weight unaffected by dialysis dose or flux. No significant effect on weight was observed during the first year of HEMO, but over time there were decreases in both estimated muscle and fat mass in all groups.
The FHN Trials showed no statistically significant between-group differences in serum albumin from baseline to 12 months. Although serum albumin concentrations have been reported to increase during the first year of dialysis, possibly related to a reduction in proteinuria or improved nutritional status, the observed increases in serum albumin in both arms of the Nocturnal Trial were not associated with residual kidney function or proximity to the initiation of dialysis therapy (data not shown).
Body weight is an imprecise nutritional marker in patients on dialysis, as weight gain may reflect increases in ECW, BCM (reported by an increase in ICW), and/or fat mass. A biphasic pattern of change in body weight has previously been described after switching from three times to six times per week dialysis. Presumably, the initial drop is due to a reduction in ECW, and subsequent weight gain results from improved appetite and increased tissue weight. In the Daily Trial, the monthly predialysis body weights in subjects randomized to the six times per week group followed such a pattern. Bioelectrical impedance analysis (BIA)-derived data at 1 month confirmed a reduction in TBW and ECW with no significant change in ICW. At 12 months, the average predialysis body weight had returned to baseline levels, whereas the reduction in ECW persisted. There was no evidence of a gain in ICW and, correspondingly, BCM. These results suggest that the body weight gain was in a non-hydrated body compartment, probably fat. Whether an increase in adiposity in patients on hemodialysis is beneficial or harmful is unknown; observational data suggest that higher body mass index is associated with enhanced survival.
We found no significant changes in ICW or phase angle with frequent compared with conventional hemodialysis. In an adult population, changes in ICW and phase angle result predominantly from changes in muscle mass, as non-muscle organ mass should remain relatively constant over time. Acidosis, inflammation, and reduced physical activity, all common in the dialysis population, are associated with decline in muscle mass, whereas increased resistive training or androgen replacement may be associated with increased muscle mass. Thus, the expected effect of change in dialysis frequency might be one of protection from loss rather than an increase in muscle mass. Our observations suggest that factors responsible for the deterioration of nutritional status seen in other studies was attenuated or possibly prevented because of patient selection, 'adequate' hemodialysis in the three times per week group, or that the period of observation was simply too short.
Our study is strengthened by data from two randomized clinical trials involving a relatively large sample of subjects reasonably representative of the North American hemodialysis population. We also included monthly measures of nutritional parameters, and used serial bioimpedance-based measures of body composition. This study also has limitations. We did not measure adiposity directly in this study. Our estimation of change in adiposity and difference in adiposity between the groups is based on subtraction of two relatively large values, body weight and TBW, from one another. Each is accompanied by a measurement error, decreasing precision in our estimate of differences in body fat mass between treatment groups. We used single-frequency BIA rather than isotope dilution methodology to determine body composition and calculated adiposity by assuming hydration of fat-free mass (FFM) of 0.73. The relative expansion of ECW found in patients on hemodialysis might lead to an underestimation of the hydration of FFM. Nevertheless, ECW/ICW varies greatly in humans as a function of age, sex, and obesity, with no significant change in the hydration of FFM measured directly.
In conclusion, frequent in-center hemodialysis significantly reduced ECW but failed to anabolize (i.e., no increase in serum albumin or BCM). Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass. Frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition.