- Author: A Brent Alper, Jr, MD, MPH; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Usually, medications employed in the management of uremia are indicated for associated metabolic and electrolyte abnormalities, such as anemia, hyperkalemia, hypocalcemia, hyperparathyroidism, and iron deficiency. Agents used include erythropoietin (EPO) for anemia, iron, phosphate binders, calcitriol for parathyroid hormone (PTH) suppression and hypocalcemia, water-soluble vitamins (eg, folate, vitamin C), and, potentially, oral bicarbonate solution or tablets for acidosis.
Medication selection and dosage depend on the patient's clinical state, which may change with the acute clinical setting.
These agents increase the reticulocyte count, hematocrit value, and hemoglobin levels.
Epoetin alfa is a purified glycoprotein produced by mammalian cells that have been modified with gene coding for human EPO. The biologic activity of epoetin alfa mimics that of human urinary EPO, which stimulates division and differentiation of committed erythroid progenitor cells and induces the release of reticulocytes from bone marrow into the bloodstream. This drug is indicated for the treatment of anemia associated with CKD or renal insufficiency.
Darbepoetin is an erythropoiesis-stimulating protein closely related to erythropoietin, a primary growth factor produced in 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 longer a half-life than epoetin alfa and may be administered weekly or biweekly.
Calcium supplements are used to correct hypocalcemia and improve symptoms associated with renal osteodystrophy. They also may be used to bind phosphate in patients with hyperphosphatemia.
Calcium carbonate is indicated for the treatment of hyperphosphatemia secondary to CKD. It effectively normalizes phosphate concentrations in dialysis patients, combining with dietary phosphate to form insoluble calcium phosphate, which is excreted in feces. Calcium carbonate is marketed in a variety of dosage forms and is relatively inexpensive.
Calcium acetate is indicated for the treatment of hyperphosphatemia secondary to CKD. It effectively normalizes phosphate concentrations in dialysis patients, combining with dietary phosphate to form insoluble calcium phosphate, which is excreted in feces.
Calcium gluconate is used for cardioprotection when potassium levels are greater than 6.5 mmol/L or for patients with electrocardiographic alterations. This agent moderates nerve and muscle performance and facilitates normal cardiac function.
Administer IV calcium gluconate or calcium chloride to stabilize myocardial conduction in a patient with cardiac arrhythmias. Calcium also moderates nerve and muscle performance by regulating the action potential excitation threshold. IV calcium is indicated in all cases of severe hyperkalemia (ie, >6 mEq/L), especially when accompanied by electrocardiographic changes.
Calcium chloride contains about 3 times more elemental calcium than an equal volume of calcium gluconate. Therefore, when hyperkalemia is accompanied by hemodynamic compromise, calcium chloride is preferred over calcium gluconate.
Essential for normal metabolism of proteins, carbohydrates, and fats and normal DNA synthesis. Used in the treatment of hyperparathyroidism, vitamin D deficiency, and renal osteodystrophy.
Paricalcitol is used for the treatment of secondary hyperparathyroidism in ESRD. It reduces PTH levels and stimulates calcium and phosphorous absorption, as well as bone mineralization.
Two known sites of action for calcitriol are the intestine and bone. Other evidence indicates that it also acts on the kidneys and parathyroid gland.
Vitamin D-3 must be converted into calcitriol in the liver and kidneys before it is fully active on its target tissues. Some evidence suggests, however, that uremic patients have a vitamin D–resistant state, because of a failure of their kidney to metabolically activate vitamin D-3 to calcitriol; calcitriol (1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3), the hormonally active form of vitamin D, increases calcium levels by promoting the absorption of calcium in the intestines and its retention in kidneys.
Doxercalciferol is a vitamin D analog (1-alpha-hydroxyergocalciferol) that does not require activation by the kidneys. It increases calcium levels by promoting the absorption of calcium in the intestines and its retention in kidneys.
Iron salts are used to correct iron deficiency symptoms.
Ferrous sulfate is a nutritionally essential, inorganic substance that is necessary for hemoglobin formation and the oxidative processes of living tissue. It effectively treats iron deficiency anemia.
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 is used to treat iron deficiency (in conjunction with erythropoietin) in patients receiving long-term hemodialysis. Iron deficiency in these patients is caused by blood loss during the dialysis procedure, increased erythropoiesis, and insufficient absorption of iron from the GI tract. There is a lower incidence of anaphylaxis with iron sucrose than with other parenteral iron products.
Ferric gluconate replaces the iron found in hemoglobin, myoglobin, and specific enzyme systems, allowing transportation of oxygen via hemoglobin.
This agent is indicated for iron replacement in adults with chronic kidney disease who have iron deficiency anemia.
These are used to reduce serum potassium levels.
This agent exchanges sodium for potassium, binds it in the gut (primarily in the large intestine), and decreases total body potassium. The oral onset of action ranges from 2-12 hours; this period is longer when the drug is taken rectally.
Antidiabetic agents stimulate the cellular uptake of potassium.
Insulin stimulates the cellular uptake of potassium within 20-30 minutes. Administer glucose along with insulin in order to prevent hypoglycemia. Monitor blood sugar levels frequently.
Phosphate binders are used to bind phosphate when, because of a high serum calcium level, calcium carbonate or acetate cannot be used.
Sevelamer is a cationic polymer that binds intestinal phosphate, which is then excreted in the feces. Sevelamer is not absorbed and does not contain calcium or aluminum ions. Binding of bile salts may also occur, which may result in lowered low-density lipoprotein (LDL) cholesterol levels.
Lanthanum carbonate is a noncalcium, nonaluminum phosphate binder indicated for the reduction of high phosphorus levels in patients with ESRD. It directly binds dietary phosphorus in the upper GI tract, thereby inhibiting phosphorus absorption.
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