sold under the name Parsabiv (Quarles & Berkoben, 2021; DiPiro et al., 2019). Cinacalcet is effective in reducing parathyroid hormone levels, as well as helping patients achieve goal calcium and phosphate levels, which can be difficult to control as CKD progresses. It has been shown to be effective in patients unable to take adequate vi- tamin D doses due to high calcium and phosphate levels, though it appears to be more effective in targeting parathyroid hormone levels when administered in combination with vitamin D products. Cinacalcet was not shown to reduce mortality in hemodialysis pa- tients under 65 years of age but may provide some benefit in old - er patients with a higher cardiovascular risk (Quarles & Berkoben, 2021; DiPiro et al., 2019). Cinacalcet is typically started at a dose of 30 mg once daily and can be increased every two to four weeks by 30 mg per dose, up to 180 mg per day. It should not be started in patients with hypo- Anemia Since anemia is so common in patients with chronic kidney dis- ease, all CKD patients should be screened for anemia by measur- ing hemoglobin levels upon initial evaluation for CKD. Patients with anemia should undergo further lab testing to evaluate the cause of anemia, including a complete blood count (CBC), serum iron, total iron-binding capacity (TIBC), percent transferrin satu- ration (TSAT), serum ferritin, serum folate, and vitamin B12 levels (Berns, 2021a). Iron administration in deficient patients is typically based on lab values, such as ferritin and transferring saturation. Most CKD pa- tients require iron supplementation when transferring saturation values are less than 20%, and/or serum ferritin is less than 100 ng/mL. Depending on the severity of anemia, iron can be admin- istered intravenously or orally. The oral form is administered to most patients, due to its inexpensive cost and easy availability, while intravenous is preferred for patients who require rapid iron repletion, have a history of not responding to iron in the past, or have severe anemia (Berns, 2021a). Several oral iron preparations are available, with the preferred agent being ferrous sulfate. Tablets containing 325 mg of ferrous sulfate contain 65 mg of elemental iron, and dosing is based on anemia severity, ranging from one to three times daily. Side ef- fects of oral iron are typically gastrointestinal in nature and include nausea, vomiting, constipation, dyspepsia, and dark stools. Ferrous gluconate typically contains less elemental iron, with 240 mg of ferrous gluconate containing 27 mg of elemental iron. This often results in a lower incidence of gastrointestinal side effects, though the lower iron content is less ideal when trying to replete iron stores. Oral iron should be administered between meals if tol- erated; intestinal iron absorption can be reduced in patients with CKD and further reduced by food or antacids. Patients who are not at their iron goals within one to three months of adequately dosed iron therapy should be switched to intravenous iron (Berns, 2021a). There are several intravenous iron products available, which ap- pear to have equal efficacy in treating iron deficiency anemia (Ber - ns, 2021a): ● Iron sucrose (Venofer) 200 mg doses given five times over two weeks. ● Ferric gluconate in sucrose complex (Ferrlecit) 250 mg weekly for three to four weeks. ● Ferumoxytol (Feraheme) 510 mg administered once, followed by a second 510 mg dose given three to eight days after the first dose. ● Ferric carboxymaltose (Injectafer) 750 mg per dose, given in two doses at least seven days apart. ● Iron dextran—not preferred for treating iron deficiency ane - mia in CKD patients due to a higher incidence of severe side effects, including anaphylaxis; if used, a 25-mg test dose is generally administered first; if tolerated, this is followed by a 500- to 1,000-mg infusion that can be repeated as needed.
calcemia. Adverse reactions associated with cinacalcet include hy- pocalcemia and gastrointestinal symptoms; GI symptoms may be reduced when the product is administered with food and typically resolved with chronic use. Serum calcium and parathyroid hor- mone levels should be frequently monitored to assess for effec- tiveness and prevent hypocalcemia (Quarles & Berkoben, 2021; DiPiro et al., 2019). Etelcalcetide, approved by the FDA in February 2017, is approved for use in hemodialysis patients with hyperparathyroidism. It is administered after dialysis three times weekly. Short-term studies showed it produced a more robust reduction in parathyroid hor- mone levels over cinacalcet, though it also caused more hypocal- cemia. Side effects with etelcalcetide include nausea, vomiting, and prolongation of the QT interval. Serum calcium and parathy- roid hormone levels should be frequently monitored (Quarles & Berkoben, 2021; DiPiro et al., 2019). Side effects associated with intravenous iron can be severe and in- clude anaphylaxis; hypotension; and gastrointestinal effects such as nausea, vomiting, and abdominal discomfort (Berns, 2021a). After ruling out or correcting iron deficiency, anemia treatment with erythropoiesis-stimulating agents may be necessary in pa- tients with hemoglobin levels less than 10 g/dL. The KDIGO Work Group recommends considering the potential benefits of reduc - ing anemia-related symptoms and avoiding blood transfusions versus the risks of potential harm of erythropoiesis-stimulating agents, such as hypertension, stroke, and vascular access loss in CKD patients with anemia. Patients who are not candidates for treatment with erythropoiesis-stimulating agents include (Berns, 2021b): ● Patients who have an active malignancy or recent history of malignancy, due to the risk of progression or recurrence of cancer. ● Patients who have experienced a stroke, due to the risk of recurrent stroke from erythropoiesis-stimulating agents. ● Inactive patients, such as those who are bedbound, have de- mentia, or have very limited functional capacity, since it is un- likely that these patients will experience the same benefit as patients who are more active and experiencing symptomatic anemia. Two erythropoiesis-stimulating agents are available for use in CKD patients with anemia. Epoetin, sold under the names Procrit and Epogen, is administered subcutaneously at an initial starting dose of approximately 50 to 100 units/kg/week. Lower doses may be appropriate, particularly in patients with hemoglobin levels near 10 g/dL. In practice, many patients are dosed at an even number of units, since vials are available in 2,000; 3,000; 4,000; 10,000; 20,000; and 40,000 units per mL vials. Therefore, many patients are started at 4,000 to 10,000 units weekly or 10,000 to 20,000 units every other week. Outcomes appear to be similar with week- ly and every other week dosing. Darbepoetin, sold under the name Aranesp, is also administered subcutaneously, with initial starting doses between 60 and 200 mcg every two to four weeks. If the choice to start an erythropoiesis-stimulating agent is made, using the lowest effective dose is recommended, as higher doses are associated with increased cardiovascular events and mortality (Berns, 2021b). Target hemoglobin levels are not well defined, though many sources recommend goals between 10 and 11.5 g/dL using the lowest effective dose of erythropoiesis-stimulating agents. Ther- apy should be individualized based on patient-specific factors. Goal hemoglobin levels over 13 g/dL are not recommended, as this may increase the risk of mortality and cardiovascular events. Adverse effects associated with erythropoiesis-stimulating agents include hypertension, hypertensive encephalopathy, seizures, car- diovascular events, increased mortality, and malignancy (Berns, 2021b).
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