Medication Summary
In chronic kidney disease (CKD), doses and dosing intervals of drugs that are excreted or metabolized renally should be adjusted according to the residual glomerular filtration rate (GFR). Some drugs are contraindicated in moderate to severe renal impairment because of potentially serious effects from drug or metabolite accumulation. Routine consultation of the appropriate references should be undertaken when prescribing any new drug to a patient with CKD.
For patients undergoing dialysis, it is extremely important to carefully check dosing guides or monitor levels when possible. These modalities differ in their clearance of drugs. Hospitalized patients undergoing other types of continuous renal replacement therapy also require close monitoring. An experienced clinical pharmacist can be invaluable in assisting to design individualized dosing regimens.
Treatments for the pathologic manifestations of CKD include the following:
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Hyperphosphatemia: Dietary phosphate binders and dietary phosphate restriction
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Hypocalcemia: Calcium supplements and possibly calcitriol
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Hyperparathyroidism: Calcitriol or vitamin D analogues
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Anemia: Iron replacement therapy, erythropoiesis-stimulating agents, or stabilizers of hypoxia-inducible factor (HIF) that inhibiting prolyl hydroxylase (PH) (eg, daprodustat)
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Cardiovascular death, heart failure: SGLT2 inhibitors
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Continued decline in kidney function: SGLT2 inhibitors, MR antagonists, ACEIs, ARBs, RAS blockers
Calcium Salts
Class Summary
Dietary phosphate binders promote the binding of phosphate in the gastrointestinal tract to reduce hyperphosphatemia.
Calcium acetate (PhosLo, Eliphos, Phoslyra)
Calcium acetate is used for the treatment of hyperphosphatemia in end-stage renal disease (ESRD). It combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces.
Calcium carbonate (Caltrate 600, Tums)
Calcium carbonate is used for the treatment of hyperphosphatemia, normalizing phosphate concentrations in patients with CKD. It can also be used as a calcium supplement in these patients.
Calcium carbonate combines with dietary phosphate to form insoluble calcium phosphate, which is excreted in feces. It is marketed in a variety of dosage forms and is relatively inexpensive.
Vitamin D Analogues
Class Summary
Vitamin D analogues are recommended in patients with CKD stages 3-5 who are not on dialysis and in whom the serum parathyroid hormone (PTH) level is elevated or has been persistently rising. Vitamin D increases the absorption of calcium in the intestines and helps to prevent secretion of calcium in the kidneys. By increasing calcium levels in serum, it helps to decrease phosphate and PTH levels, as well as bone resorption.
Calcitriol (Rocaltrol, Calcijex, Vectical)
Calcitriol (1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3), the potent active metabolite of vitamin D, can be used to suppress PTH production and secretion in secondary hyperparathyroidism. In addition, calcitriol can alleviate hypocalcemia in CKD by increasing intestinal calcium absorption and helping to prevent secretion of calcium in the kidneys.
Doxercalciferol (Hectorol)
Doxercalciferol is a vitamin D analogue (1-alpha-hydroxyergocalciferol) that does not require activation by the kidneys. It is metabolized to the active form of vitamin D. Doxercalciferol is indicated for the treatment of secondary hyperparathyroidism in patients with CKD.
Paricalcitol (Zemplar)
Paricalcitol is a synthetic vitamin D analogue that binds and activates vitamin D receptors in the kidneys, parathyroid glands, intestines, and bones. It is used for the prevention and treatment of secondary hyperparathyroidism associated with CKD stages 3-4 and stage 5 patients on hemodialysis or peritoneal dialysis. It reduces PTH levels, improves calcium and phosphorus homeostasis, and stimulates bone mineralization.
Calcifediol (Rayaldee)
Extended-release formulation of calcifediol (25-hydroxyvitamin D3), a prohormone of the active form of vitamin D3. Calcifediol is converted to calcitriol by CYP27B1, also called 1-alpha hydroxylase, primarily in the kidney. Calcitriol binds to the vitamin D receptor in target tissues and activates vitamin D responsive pathways that result in increased intestinal absorption of calcium and phosphorus and reduced parathyroid hormone synthesis. It is indicated for secondary hyperparathyroidism associated with vitamin D insufficiency in patients with stage 3 or 4 chronic kidney disease (CKD) and serum total 25-hydroxyvitamin D levels <30 ng/mL.
PO4 Scavengers
Class Summary
Dietary phosphate binders promote the binding of phosphate in the gastrointestinal tract to reduce hyperphosphatemia.
Lanthanum carbonate (Fosrenol)
Lanthanum carbonate is a noncalcium, nonaluminum phosphate binder indicated for the reduction of high phosphorus levels in patients with stage 5 kidney disease. It dissociates into ions in the upper gastrointestinal tract, and these ions directly bind to dietary phosphate, forming insoluble lanthanum phosphate complexes. It therefore inhibits phosphorus absorption.
Sevelamer (Renagel, Renvela)
Sevelamer is indicated for the reduction of serum phosphorus levels in patients with CKD on hemodialysis. This agent binds dietary phosphate in the intestine, thus inhibiting its absorption. In patients on hemodialysis, sevelamer treatment results in fewer hypercalcemic episodes than does calcium acetate therapy.
Sucroferric oxyhydroxide (Velphoro)
Sucroferric oxyhydroxide is an iron-based, calcium-free phosphate binder. When it is taken with meals, dietary phosphate is adsorbed in the GI tract and eliminated in the feces. It is indicated for control of serum phosphorus levels in patients with chronic kidney disease on hemodialysis.
Hematopoietic Growth Factors
Class Summary
Growth factors are used to treat anemia of CKD by stimulating red blood cell (RBC) production.
Epoetin alfa (Epogen, Procrit)
Epoetin alfa stimulates the division and differentiation of committed erythroid progenitor cells. It induces the release of reticulocytes from the bone marrow into the bloodstream.
Darbepoetin (Aranesp)
Darbepoetin is an erythropoiesis-stimulating protein closely related to erythropoietin, a primary growth factor produced in the kidney that stimulates the development of erythroid progenitor cells. Its mechanism of action is similar to that of endogenous erythropoietin, which interacts with stem cells to increase red cell production.
Darbepoetin contains 5 N-linked oligosaccharide chains, whereas epoetin alfa contains 3 such chains. Darbepoetin has a longer half-life than epoetin alfa and may be administered weekly or biweekly.
Hypoxia-Inducible Factors Inhibitors
Class Summary
An alternative to the administration of exogenous ESAs is the use of agents that stimulate endogenous erythropoietin production in the kidney and nonrenal tissues. One class of agents works to stabilize hypoxia-inducible factor (HIF) by inhibiting prolyl hydroxylase (PH) enzymes. [84]
Daprodustat (Jesduvroq)
Inhibition of oxygen-sensing prolyl hydroxylase enzymes stabilizes hypoxia-inducible factors, which can lead to transcription of erythropoietin and other genes involved in the correction of anemia. Indicated for treatment of anemia due to chronic kidney disease (CKD) in adults on dialysis for at least 4 months.
Iron Products
Class Summary
Iron salts are nutritionally essential inorganic substances used to treat anemia.
Ferrous sulfate (Feosol, Fer-In-Sol, Slow FE, Fer-iron, MyKidz Iron 10)
Ferrous sulfate is used as a building block for hemoglobin synthesis in patients with anemia of CKD who are being treated with erythropoietin.
Iron dextran complex (Dexferrum, INFed)
Iron dextran is used to treat microcytic, hypochromic anemia resulting from iron deficiency, and to replenish iron stores in individuals on erythropoietin therapy, when oral administration is infeasible or ineffective. A 0.5-mL (0.25 mL in children) test dose should be administered prior to starting therapy. This agent is available as 50 mg iron/mL (as dextran).
Iron sucrose (Venofer)
Iron sucrose is used to treat iron deficiency anemia (in conjunction with erythropoietin) in patients with dialysis- and non–dialysis-dependent CKD. Iron deficiency in these patients is caused by blood loss during the dialysis procedure, increased erythropoiesis, and insufficient absorption of iron from the gastrointestinal tract. There is a lower incidence of anaphylaxis with iron sucrose than with other parenteral iron products.
Ferric gluconate (Ferrlecit, Nulecit)
Ferric gluconate replaces the iron found in hemoglobin, myoglobin, and specific enzyme systems, allowing transportation of oxygen via hemoglobin.
Ferumoxytol (Feraheme)
Ferumoxytol is indicated for iron replacement in adults with CKD who have iron deficiency anemia. Iron is released from an iron-carbohydrate complex in reticuloendothelial system macrophages. The released iron is transported into storage pools or plasma transferrin, which allows the iron to be incorporated into hemoglobin.
Ferric pyrophosphate (Triferic)
Contains iron in the form of soluble ferric pyrophosphate citrate that is added to hemodialysate solution and administered to patients by transfer across the dialyzer membrane. Iron delivered into the circulation binds to transferrin for transport to erythroid precursor cells to be incorporated into hemoglobin.
Ferric carboxymaltose (Injectafer)
Ferric carboxymaltose is a non-dextran IV colloidal iron hydroxide in complex with carboxymaltose, a carbohydrate polymer that releases iron. It is indicated for iron deficiency anemia (IDA) in adults who have intolerance or an unsatisfactory response to oral iron. It is also indicated for IDA in adults with nondialysis- dependent chronic kidney disease.
Calcimimetics
Class Summary
A calcimimetic mimics calcium at the parathyroid hormone (PTH) receptor and reduces PTH levels.
Etelcalcetide (Parsabiv)
Calcimimetic agent that allosterically modulates the calcium-sensing receptor (CaSR) and enhances activation of the receptor by extracellular calcium. Activation of the CaSR on parathyroid chief cells decreases PTH secretion. It is indicated for secondary hyperparathyroidism in patients with CKD on dialysis.
Cinacalcet (Sensipar)
Cinacalcet directly lowers intact PTH levels by increasing the sensitivity to extracellular calcium of calcium-sensing receptors on chief cells of the parathyroid glands. It also results in a concomitant decrease in serum calcium. It is indicated for secondary hyperparathyroidism in patients with CKD on dialysis.
Sodium-Glucose Transporter-2 (SGLT2) Inhibitors
Class Summary
Sodium-glucose cotransporter 2 (SGLT2), expressed in the proximal renal tubules, is responsible for the majority of the reabsorption of filtered glucose from the tubular lumen. Inhibition of SGLT2 reduces reabsorption of filtered glucose and thereby promotes urinary glucose excretion.
Inhibition of SGLT also reduces sodium reabsorption and increases the delivery of sodium to the distal tubule. This may influence several physiological functions including, but not restricted to, lowering both pre- and afterload of the heart and downregulation of sympathetic activity, and decreased intraglomerular pressure, which is mediated by increased tubuloglomerular feedback.
Dapagliflozin (Farxiga)
Indicated to reduce risk of sustained eGFR decline, ESKD, cardiovascular death, and hospitalization for heart failure in adults with CKD who are at risk of progression.
Canagliflozin (Invokana)
Indicated to reduce the risk of ESKD, doubling of serum creatinine, cardiovascular death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria.
Mineralocorticoid Receptor Antagonists
Class Summary
Mineralocorticoid receptor (MR) over activation is thought to contribute to fibrosis and inflammation in both epithelial (eg, kidney) and nonepithelial (eg, heart, blood vessels) tissues. MR-mediated sodium reabsorption in the kidneys is also inhibited.
Finerenone (Kerendia)
Finerenone is a nonsteroidal, selective MR antagonist, which is activated by aldosterone and cortisol and regulates gene transcription. Finerenone has a high potency and selectivity for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors. It is indicated to reduce risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adults with CKD associated with type 2 diabetes
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Chronic kidney disease: Calciphylaxis due to secondary hyperparathyroidism.
