Extended Hours Dialysis Reduced Serum Phosphate Levels in Patients with CKD-MBD

Patients with chronic kidney disease
(CKD) commonly experience abnormalities of mineral and bone metabolism,
contributing significantly to increased rates of mortality and morbidity,
including cardiovascular disease and fracture. The term chronic
kidney-disease-mineral and bone disorder (CKD-MBD) encompasses disturbances of
mineral metabolism, renal bone disease, and vascular calcification in
combination with patient-level outcomes of fracture, cardiovascular disease,
and mortality in patients with CKD.

Phosphate binders, vitamin D
analogues, and parathyroidectomy are standard of care for CKD-MBD. Treatment is
complex and is not firmly evidence-based; further, there is potential for harm
with current treatments. Conventional three times a week dialysis is often
insufficient to attain negative phosphate balance and fewer than half of
dialysis patients achieve levels suggested by several clinical practice guidelines.
Low dietary protein intake and malnutrition can result from aggressive
adherence to a low-phosphate diet and the large number of phosphate binder
tablets required to control hyperphosphatemia creates high pill burden,
increased disease intrusion, abdominal symptoms, and potential conflict with
other medications.

In the ACTIVE Dialysis (A Clinical
Trial of Intensive Dialysis) study, extended hours dialysis reduced serum
phosphate but did not cause changes in parathyroid hormone (PTH) or serum
calcium. Researchers, led by Zhipeng Zhan, MD, and Brendon Smyth, MD,
conducted a secondary analysis of data from the ACTIVE Dialysis trial to
examine the impact of extended hours dialysis on CKD-MBD markers in
prespecified patient groups, accounting for concurrent changes in non-dialytic
CKD-MBD therapies. Results of the secondary analysis were reported online in BMC
Nephrology [doi.org/11.1186/s12882-019-1438-3].

The primary outcome of interest was
the mean difference in each parameter between the extended (n=100) and standard
dialysis arms (n=100), adjusted for confounding participant characteristics and
for changes in associated non-dialytic therapies: total number of phosphate
binders, use of calcitriol/alfacalcidol, dose of cinacalcet, and dialysate
calcium. Secondary outcomes included interactions between subgroups derived
from six pre-defined criteria and the unadjusted mean difference in parameters
between treatment arms.

A total of 200 participants were
recruited from China (62.0%), Australia (29.0%), Canada, (5.5%), and New
Zealand (3.5%). The groups were similar in concentrations of serum phosphate,
corrected calcium, and intact PTH. In the standard arm, median total weekly
dialysis hours during the study period was 12, compared with 24 in the extended
arm. In the standard arm, use of hemodiafiltration was more common during the
study period than in the extended arm (22.2% vs 14.2% of sessions); the
difference did not reach statistical significance. There were no significant
differences in dialysate concentrations of sodium, potassium, or calcium.

During the study period, blood flow
rates were lower in the extended arm compared with the standard arm (250 mL/min
vs 280 mL/min). At 90.6% of study visits, dialysate flow rate was 500 mL/min
and median flow rates did not differ (500 mL/min) (a small number of outlying
values resulted in mean dialysate flow rates being lower in the extended arm).
In the standard arm, one participant had a fracture and two had
parathyroidectomies; in the extended arm, there was one fracture and one
parathyroidectomy.

Extended hours dialysis resulted in reduction
in use of phosphate binders (–0.83 tablets per day; 95% confidence interval
[CI], –1.16 to –0.04; P=.04). In adjusted analyses, there were no
differences in type of phosphate binder, use of vitamin D, dose of cinacalcet,
or dialysate calcium.

Over the duration of the study,
achievement of serum phosphate levels within the target range was more common
in the extended arm (relative risk [RR], 1.21; 95% CI, 1.04-1.43; P=.016).
There were no differences between the two groups in the proportion of patients
who achieved target ranges for serum calcium (RR, 1.03; 95% CI, 0.93-1.14; P=.61)
and PTH (RR, 1.09; 95% CI, 0.89-1.34; P=.40).

Across the tested subgroups, the
impact of extended hours dialysis on serum phosphate, calcium, and PTH was
generally consistent. Exceptions were the significant interaction between the
effect of treatment allocation on phosphate and both baseline level of PTH (P
for interaction=.043) and dialysis location (P for interaction=.046), such that
participants with high baseline PTH and dialyzing at an institution experienced
a greater reduction in serum phosphate with extended hours dialysis. There was
also a significant interaction between the effect of treatment allocation on
PTH and baseline phosphate (P for interaction=.019); participants with
low baseline serum phosphate had a small increase in PTH if assigned to
extended hours dialysis.

There were some limitations to the
findings, including the relatively small cohort size, limiting the power of the
study to detect subgroup differences; the short study duration; and the lack of
serum levels of calcidiol (25-hydroxyvitamin D).

In conclusion, the researchers said,
“The improvement in serum phosphate associated with extended hours hemodialysis
was independent of changes in other CKD-MBD therapies and was consistent across
a range of important patient subgroups. The observed differences in the impact
of extended hours dialysis on phosphate seen in those with high baseline PTH or
dialyzing in an institution, or on PTH in those with low phosphate require
confirmation in larger studies.”

Takeaway Points

1. Chronic kidney disease-mineral and
   bone disorder (CKD-MBD) is associated with changes in phosphate, calcium, and
   parathyroid hormone (PTH) in patients on hemodialysis. Researchers conducted an
   analysis of data from the ACTIVE Dialysis study that compared conventional
   dialysis  (≤18 h/week) with extended
   hours dialysis (≥24 h/week).
2. Phosphate binder use was reduced
   among patients assigned to extended hours dialysis; there was no difference in
   type of phosphate binder.
3. In adjusted analysis, there was an
   association between extended hours dialysis and lower phosphate; there was no significant
   change in serum calcium or PTH among patients in the extended hours arm
   compared with the standard arm.