Dialysate Calcium Concentration and Mineral Metabolism in Long and Long-Frequent Hemodialysis: A Systematic Review and Meta-analysis for a Canadian Society of Nephrology Clinical Practice Guideline

Background Patients treated with conventional hemodialysis (HD) develop disorders of mineral metabolism that are associated with increased morbidity and mortality. More frequent and longer HD has been associated with improvement in hyperphosphatemia that may improve outcomes. Study Design Systematic review and meta-analysis to inform the clinical practice guideline on intensive dialysis for the Canadian Society of Nephrology. Setting & Population Adult patients receiving outpatient long (≥5.5 hours/session; 3-4 times per week) or long-frequent (≥5.5 hours/session, ≥5 sessions per week) HD. Selection Criteria for Studies We included clinical trials, cohort studies, case series, case reports, and systematic reviews. Interventions Dialysate calcium concentration ≥1.5 mmol/L and/or phosphate additive. Outcomes Fragility fracture, peripheral arterial and coronary artery disease, calcific uremic arteriolopathy, mortality, intradialytic hypotension, parathyroidectomy, extraosseous calcification, markers of mineral metabolism, diet liberalization, phosphate-binder use, and muscle mass. Results 21 studies were identified: 2 randomized controlled trials, 2 reanalyses of data from the randomized controlled trials, and 17 observational studies. Dialysate calcium concentration ≥1.5 mmol/L for patients treated with long and long-frequent HD prevents an increase in parathyroid hormone levels and a decline in bone mineral density without causing harm. Both long and long-frequent HD were associated with a reduction in serum phosphate level of 0.42-0.45 mmol/L and a reduction in phosphate-binder use. There was no direct evidence to support the use of a dialysate phosphate additive. Limitations Almost all the available information is related to changes in laboratory values and surrogate outcomes. Conclusions Dialysate calcium concentration ≥1.5 mmol/L for most patients treated with long and long-frequent dialysis prevents an increase in parathyroid hormone levels and decline in bone mineral density without increased risk of calcification. It seems prudent to add phosphate to the dialysate for patients with a low predialysis phosphate level or very low postdialysis phosphate level until more evidence becomes available.