How should treatment be approached for patients with CKD stage 5?
Patients with stage 5 Chronic Kidney Disease who have not been previously treated generally present with hyperphosphatemia, hyperparathyroidism, and very low calcitriol concentrations, and may have low, normal, or elevated serum calcium.
Furthermore, most of these patients are also calcidiol deficient.
Similar to patients with Chronic Kidney Disease stages 3 and 4, there is a lack of prospective clinical studies demonstrating that correction of mineral abnormalities improve hard clinical endpoints.
However, expert consensus agrees that therapy should definitely be focused to control serum phosphate to at least 5.5 mg/dL, if not to normal values by the use of adequate dialysis, dietary phosphate restriction, and phosphate binders. The use of calcium-containing binders (calcium carbonate or calcium acetate) should be limited to less than 1500 mg of calcium a day.
Calcium acetate is a more effective phosphate binder per mg of calcium compared with calcium carbonate. Thus the use of calcium carbonate may result in greater absorption of calcium relative to phosphate binding, compared with calcium acetate. If patients have evidence of vascular calcifications, calcium-containing binders should be avoided.
The non-calcium-containing binders include either sevelamer, lanthanum, or iron-based compounds.
Both sevelamer, as either sevelamer HCl or carbonate, and lanthanum carbonate have been available for many years and have proven to be effective with few side effects or long-term risks.
However, the dose for sevelamer generally requires three to four times the number of pills than that required for lanthanum with comparable phosphate control.
Two iron-based phosphate binders, ferric citrate and sucroferric oxyhydroxide, are effective, with few side effects. Ferric citrate increases iron loading and lowers erythropoietin stimulating agent (ESA) requirements.
Succroferric oxyhydroxide is as effective as sevelamer carbonate, with about a third of the pill burden. Succroferric oxyhydroxide does not significantly affect iron balance or ESA dosing.
If patients have extremely elevated serum phosphorus, a short course of aluminum-containing phosphate binder may be considered; however, its long-term use should be avoided because of the risk of aluminum toxicity.
Hyperparathyroidism and calcitriol deficiency could be addressed with the use of VDRAs. Calcitriol is effective but carries a greater risk of causing hypercalcemia and/or hyperphosphatemia, whereas paricalcitol appears to have the lowest risk for hypercalcemia and hyperphosphatemia.
Doxercalciferol, a prohormone, is also effective at reducing PTH, but may have a higher incidence of hypercalcemia and/or hyperphosphatemia than paricalcitol.
Only one study has directly compared VDRAs in patients receiving dialysis, and that was between calcitriol and paricalcitol, which demonstrated comparable reduction in PTH but greater incidence of hypercalcemia and increase in calcium × phosphate product in those receiving calcitriol.
Unfortunately, no prospective studies have yet been performed that have demonstrated the use of VDRAs improve hard clinical outcomes, such as survival, fractures, and cardiovascular events.
The calcimimetic, cinacalcet lowers PTH, calcium, and phosphate concentrations in ESKD patients.
The EVOLVE study, a 5-year prospective trial of cinacalcet, used in combination of VDRAs, did not reduce mortality, cardiovascular disease, or fractures, but was associated with decrease in parathyroidectomies, compared with VDRA use alone. In addition to cinacalcet, there is a parenteral calcimimetic, elecalcetide, which also appears to be similarly effective to cinacalcet.
There has been some controversy as to the optimal PTH concentration to achieve in patients with stage 5 CKD. K/DIGO has expanded the K/DOQI range (150 to 300 pg/mL) to two to nine times the upper limit of normal for the particular PTH assay being used.
The problem is that it has not clearly been defined as to what PTH values are consistently associated with normal bone histology. Furthermore, it has been noted that there are great discrepancies between various PTH assays. Thus a reasonable approach is to manage patients with only one PTH assay, to follow trends in PTH levels (as suggested by K/DIGO), and to use appropriate clinical judgment in managing PTH levels.
Whether it is reasonable to correct the calcidiol deficiency by replacing nutritional vitamin D with cholecalciferol or ergocalciferol remains open for debate. To date, there is no data on the use of ER calcifediol in patients with stage 5 Chronic Kidney Disease.