Iron-based phosphate binders Sucroferric oxyhydroxide is an iron-based chewable phosphate binder sold under the name Velphoro. It is a U.S. Food and Drug Administration (FDA) approved for treating hyperphosphatemia in patients with a GFR of less than 15 mL/min/1.73m 2 . Sucroferric oxyhydroxide has comparable efficacy to sevelamer in reducing phosphate levels. Sucroferric oxyhydroxide appears to have more frequent side effect rates and more frequent drug discontinuation rates due to side effects. Adverse reactions are similar to those experienced with administration of iron and include diarrhea, nau- sea, constipation, vomiting, and changes in taste. A typical start- ing dose of sucroferric oxyhydroxide is 2.5 g three times daily with meals (Berkoben & Quarles, 2021; DiPiro et al., 2019). Aluminum-based phosphate binders Aluminum hydroxide is an effective phosphate binder, but due to the risk of aluminum toxicity in patients with chronic kidney dis- ease, it is recommended only for short-term treatment of severe hyperphosphatemia for less than four weeks. Its use is infrequent Hyperparathyroidism: Vitamin D analogs Since reduced levels of activated vitamin D in chronic kidney dis- ease patients can contribute to the development of hyperpara- thyroidism, treatment with calcitriol or vitamin D analogs may be necessary to maintain normal parathyroid hormone levels. More selective vitamin D analogs such as paricalcitol or doxercalciferol were developed to reduce the risk of hypercalcemia and hyper- phosphatemia associated with calcitriol, but the selectivity of these agents has not been consistently proven in chronic kidney disease patients. Studies show all vitamin D analogs demonstrate the potential to increase calcium and phosphate levels, particular- ly at high doses, leading to increased mortality; adding a phos- phate binder may be necessary to maintain normal phosphate levels (Quarles & Berkoben, 2021). All three agents appear to have comparable efficacy in reducing parathyroid hormone levels, and studies have not shown a prefer- ence for one agent over others. Price and insurance coverage may Calcitriol Calcitriol is the activated form of vitamin D. It is available in an oral preparation, associated with the brand name Rocaltrol, and an IV preparation, associated with the brand name Calcijex. Oral preparations are typically used in chronic kidney disease patients; IV administration is generally reserved for dialysis patients with Paricalcitol Paricalcitol is a vitamin D analog approved for the treatment of hyperparathyroidism, sold under the brand name Zemplar. It is typically started at a dose of 1 mcg daily and adjusted based on parathyroid hormone, calcium, and phosphate levels every two to four weeks (Quarles & Berkoben, 2021; DiPiro et al., 2019). Paricalcitol appears to have comparable effectiveness to calcitri- ol in reducing parathyroid hormone levels. However, a long-term study has found significantly lower mortality rates with paricalcitol Doxercalciferol Doxercalciferol is another vitamin D analog approved for the treat- ment of hyperparathyroidism, sold under the brand name Hectorol. It is available in both oral and IV forms, though the IV form is typ- ically reserved for severe cases of hyperparathyroidism in dialysis patients. In nondialysis patients, it is started at a dose of 1 mcg daily and adjusted based on parathyroid hormone, calcium, and phos- phate levels every two weeks up to a maximum dose of 3.5 mcg/ day (Quarles & Berkoben, 2021; DiPiro et al., 2019). Hyperparathyroidism: calcimimetics Calcimimetics work by increasing the sensitivity of the calcium re- ceptor in the parathyroid gland to calcium, which regulates para- thyroid hormone secretion. This allows for a reduction in serum parathyroid hormone levels, as well as a decrease in calcium and
Ferric citrate, sold under the brand name Auryxia, is another iron- based phosphate binder used to treat hyperphosphatemia. While effective in reducing serum phosphorus levels, citrate in any form has been proven to increase intestinal absorption of aluminum, thus increasing aluminum toxicity risk. Since this can be a poten- tially severe reaction in patients with chronic kidney disease, some references recommend avoiding all citrate products in chronic kidney disease patients. Ferric citrate can also increase iron levels, and potentially cause iron overload, so ferritin and iron saturation levels should be monitored at baseline and periodically thereaf- ter. Other adverse reactions are related to the iron content and include nausea, vomiting, diarrhea, constipation, and dark stools (Berkoben & Quarles, 2021; DiPiro et al., 2019). in chronic kidney disease patients due to the aluminum toxicity risk, which can cause anemia, muscle and bone pain, dementia, and vitamin D–resistant osteomalacia (Berkoben & Quarles, 2021; DiPiro et al., 2019). be the deciding factor, with many insurance companies preferring calcitriol due to its lower cost (Quarles & Berkoben, 2021). Calcitriol, paricalcitol, and doxercalciferol should not be admin- istered until blood phosphorus and calcium levels have been controlled. This is due to the risk of increasing calcium levels in the presence of high phosphorus levels, which can lead to pre- cipitation, increasing the risk of vascular calcification (Quarles & Berkoben, 2021). Treatment regimens that limit the dose of calcitriol or vitamin D analogs may be beneficial due to the ability of these agents to induce hypercalcemia and hyperphosphatemia. Despite this risk, a number of benefits have been noted with administration of cal - citriol and vitamin D analogs, including reduced all-cause death and cardiovascular mortality in hemodialysis patients with ade- quate vitamin D levels (Quarles & Berkoben, 2021). significant hypocalcemia. Oral administration can be started at a dose of 0.25 mcg once per day and adjusted after four to eight weeks based on calcium and parathyroid hormone levels. Calcitri- ol should be discontinued if hypercalcemia develops (Quarles & Berkoben, 2021; DiPiro et al., 2019). when compared with calcitriol in dialysis patients, beginning after 12 months of treatment. Paricalcitol was also associated with less elevation in serum phosphate and calcium levels. Unfortunately, this study was not randomized and had significant differences in patient baseline characteristics, so this trial alone is not considered a reason to prefer paricalcitol over other agents (Quarles & Berkoben, 2021; DiPiro et al., 2019). Self-Assessment Quiz Question #7 Which of the following vitamin D analogs is the preferred medi- cation for the treatment of hyperparathyroidism? a. Paricalcitol. b. Doxercalciferol. c. Calcitriol. d. There is not a preference for one agent over another. phosphate levels. Unlike vitamin D analogs, calcimimetics can be administered in patients with hyperphosphatemia. There are two calcimimetics available in the U.S.: cinacalcet, an oral medication sold under the name Sensipar, and etelcalcetide, an IV product
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