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.”
- 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).
- Phosphate binder use was reduced among patients assigned to extended hours dialysis; there was no difference in type of phosphate binder.
- 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.