Pediatric Polycystic Kidney Disease Medication
- Author: Priya Verghese, MD, MPH; Chief Editor: Craig B Langman, MD more...
Medication Summary
Drug therapy is not currently a component of the standard of care in this condition. Medications are used only to treat the complications that arise from the disease process.
Because of the availability of animal models, preclinical trials have been developed, and promising candidate drugs have been identified for clinical trials.[12] The role of cyclic adenosine monophosphate (cAMP) in cystogenesis provided the rationale for preclinical trials of vasopressin V2 receptor antagonists. One of these drugs, OPC-31260, substantially reduced concentrations of cAMP and inhibited cyst development in models of both types of polycystic kidney disease and nephronophthisis.
An antagonist with high potency and selectivity for the human VPV2R (tolvaptan) has been shown to be an effective treatment in the rat model of autosomal recessive polycystic kidney disease and the Pkd2 mouse model of autosomal dominant polycystic kidney disease. These drugs have no effect on liver cysts. Somatostatin that acts on SST2 receptors inhibits cAMP accumulation in the kidney and in the liver. Octreotide, a synthetic, metabolically stable somatostatin analogue, halts the expansion of hepatic cysts in a rat model of polycystic kidney disease in vitro and in vivo.
Other drugs shown to be effective in preclinical trials for the treatment of human polycystic kidney disease include inhibitors of epidermal growth factor receptor, Erb-B2 tyrosine kinase, and Src kinase.[13]
Once children with autosomal recessive polycystic kidney disease develop chronic kidney disease, they require management of anemia with iron and erythropoietin; prevention of metabolic bone disease with calcium supplements, phosphate binders, and parathyroid-suppressing medication; and growth hormone to counter the growth-limiting effects of uremia.
If evidence of concentrating defects is observed in infants without significant renal insufficiency, thiazides may be useful. Bicarbonate supplements may be necessary for correction of metabolic acidosis.
Systemic hypertension should be aggressively treated with antihypertensive medication. Angiotensin-converting enzyme (ACE) inhibitors are the drugs of choice. Calcium channel blockers, beta blockers, and the judicious use of diuretics are also potential options. Antibiotics are used to treat urinary tract infections.
Iron Salts
Class Summary
Iron salts are used to replenish iron stores. The body stores iron in compounds called ferritin and hemosiderin for future use in the production of hemoglobin. Iron absorption is a variable of the existing body iron stores, the form and quantity in foods, and the combination of foods in the diet. The ferrous form of inorganic iron is more readily absorbed.
Ferrous sulfate (Feosol, MyKidz Iron, Fer-Iron)
Ferrous sulfate is a source of iron for hemoglobin synthesis in the treatment of anemia of chronic renal failure. This agent is used with erythropoietin to prevent iron stores depletion. Oral solutions and chewable tablet formulations of ferrous iron salts are available for use in pediatric populations.
Sodium ferric gluconate complex (Ferrlecit, Nulecit)
Sodium ferric gluconate complex is used to treat microcytic hypochromic anemia due to iron deficiency when oral administration is unfeasible or ineffective as well as to replenish iron stores in individuals on erythropoietin therapy who cannot take or tolerate oral iron supplementation.
Iron sucrose (Venofer)
Iron sucrose is a polynuclear iron (III) hydroxide in sucrose for intravenous use. This agent contains no preservatives or dextran polysaccharides. Iron sucrose is used to treat microcytic hypochromic anemia due to iron deficiency when oral administration is unfeasible or ineffective, as well as to replenish iron stores in individuals on erythropoietin therapy who cannot take or tolerate oral iron supplementation.
Colony Stimulating Factors
Class Summary
Colony stimulating factors are used to stimulate blood cell production. Endogenous erythropoietin stimulates red blood cell (RBC) hematopoiesis. Recombinant human erythropoietin (epoetin alfa) and darbepoetin stimulate erythropoiesis in anemic conditions.
Epoetin alfa (Epogen, Procrit)
Epoetin alfa stimulates the division and differentiation of committed erythroid progenitor cells and induces the release of reticulocytes from the bone marrow into the blood stream.
Darbepoetin alfa (Aranesp)
Darbepoetin alfa stimulates the division and differentiation of committed erythroid progenitor cells and induces the release of reticulocytes from the bone marrow into the blood stream.
Phosphate Binders
Class Summary
Phosphate binding agents are indicated if phosphate elevation is uncontrolled by dietary phosphate restriction. Calcium phosphate binders are typically the initial therapy for hyperphosphatemia. Calcium supplements and calcitriol may also possibly be used for hypocalcemia.
Calcium acetate (Eliphos, PhosLo)
Calcium acetate is indicated for the treatment of hyperphosphatemia secondary to chronic renal failure. This agent combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces. One caplet or tablet of calcium acetate 667 mg is equivalent to 169-mg elemental calcium (ie, 1 g calcium acetate equivalent to 250-mg of elemental calcium).
Calcium carbonate (Caltrate, Tums, Alcalak)
Calcium carbonate is used to treat hyperphosphatemia in chronic renal failure. This agent combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces. Calcium carbonate is also indicated for hypocalcemia. Calcium carbonate 1 g is equivalent to 400 mg of elemental calcium.
Sevelamer (Renagel, Renvela)
Sevelamer is indicated to reduce serum phosphorous in patients with end-stage renal disease (ESRD). This agent binds dietary phosphate in the intestine, thus inhibiting its absorption as well as reduces the incidence of hypercalcemic episodes in patients on hemodialysis compared with patients receiving calcium acetate treatment.
Vitamin D Analogues
Class Summary
Hyperparathyroidism is treated with calcitriol or other active vitamin D analogues. These drugs may also be used to treat hypocalcemia.
Calcitriol (Rocaltrol, Calcijex, Vectical)
Calcitriol is a primary active metabolite of vitamin D-3. This agent increases calcium levels in serum by promoting absorption of calcium in the intestines and retention in the kidneys. Calcitriol decreases excessive serum phosphatase levels and parathyroid levels as well as decreases bone resorption.
Calcitriol should be used in patients with renal failure who are unable to convert the inactive prohormone forms to the active metabolite. This agent is available in oral and parenteral formulations. This active form of vitamin D is used in cases of proximal renal tubular acidosis (pRTA) as multitherapy with large quantities of alkali and potassium supplementation and is also used to suppress parathyroid production and secretion in secondary hyperparathyroidism and for treatment of hypocalcemia in chronic renal failure by increasing intestinal calcium absorption.
Paricalcitol (Zemplar)
Paricalcitol, an active form of vitamin D, is formed through the removal of the 19th carbon group and modifications to the side chain of calcitriol, thus reducing the calcemic effect. This agent has been reported to suppress parathyroid hormone (PTH) without significant impact on calcium, phosphorus, or calcium-phosphorus product. Paricalcitol increases calcium levels in serum by promoting absorption of calcium in intestines and retention in kidneys, decreases excessive serum phosphatase levels and PTH levels, and decreases bone resorption.
This agent should be used in patients with renal failure who are unable to convert the inactive prohormone forms to the active metabolite. It is also used to suppress parathyroid production and secretion in secondary hyperparathyroidism and for treatment of hypocalcemia in chronic renal failure by increasing intestinal calcium absorption. Paricalcitol is available in oral and parenteral formulations.
Doxercalciferol (Hectorol)
Doxercalciferol is a vitamin D analogue (1-alpha-hydroxyergocalciferol) that does not require activation by the kidneys but does require hydroxylation in the liver to be converted to an active vitamin D metabolite. This agent controls intestinal absorption of dietary calcium, tubular reabsorption of calcium by the kidneys, and in conjunction with parathyroid hormone, the mobilization of calcium from skeleton. Doxercalciferol is indicated for the treatment of secondary hyperparathyroidism in end-stage renal disease (ESRD).
Growth Hormones
Class Summary
Growth hormones are used pharmacologically as growth-promoting agents to help optimize growth in developing children with chronic kidney disease (CKD).
Growth hormone (Nutropin, Saizen, Genotropin)
Growth hormone is a human growth hormone (hGH) produced by recombinant DNA technology and whose use results in stimulation of linear growth. This agent stimulates erythropoietin, which increases red blood cell mass.
Growth hormone is currently widely available in subcutaneous (SC) injection form. Adjust the dose gradually based on clinical and biochemical responses assessed at monthly intervals, including body weight, waist circumference, serum insulinlike growth factor-1 (IGF-1), insulinlike growth factor binding protein-3 (IGFBP-3), serum glucose, lipids, thyroid function, and whole body dual-energy x-ray absorptiometry (DEXA). In children, assess treatment response based on height and growth velocity. Continue treatment until the child's final height or epiphysial closure or both have been recorded.
Calcimimetic Agents
Class Summary
Calcimimetic agents reduce parathyroid hormone (PTH) levels.
Cinacalcet (Sensipar)
Cinacalcet directly lowers intact parathyroid hormone (iPTH) levels by increasing the sensitivity of the calcium-sensing receptor on chief cell of the parathyroid gland to extracellular calcium. This process also results in concomitant serum calcium decrease. Cinacalcet is indicated for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.
Diuretic Agents
Class Summary
These agents are used to remove excess fluid in children with edema secondary to renal disease and are administered as an adjunct to manage hypertension and excess fluid.
Furosemide (Lasix)
Furosemide is a loop diuretic. It is often effective in removing fluid even when the glomerular filtration rate is reduced secondary to nephritis. This agent increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and the distal renal tubule.
Hydrochlorothiazide (Microzide)
Hydrochlorothiazide (HCTZ) acts on the distal nephron to impair sodium reabsorption, enhancing sodium excretion. It has been in use for more than 40 years and is generally an important agent for the treatment of essential hypertension.
ACE Inhibitors
Class Summary
These agents reduce the systemic arterial blood pressure, reducing injury caused by elevated blood pressure. They may not only reduce cardiovascular risk but also slow progression of renal failure. ACE inhibitors may also slow progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms.
A dry cough is a common adverse effect of ACE inhibitors. If the cough occurs with one ACE inhibitor, it is likely to occur with another. A reasonable substitute for an ACE inhibitor if a cough develops is an ARB, such as losartan, valsartan, or candesartan.
Captopril
Captopril, a competitive ACE inhibitor, prevents the conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, increasing levels of plasma renin and reducing aldosterone secretion. It has been clinically used for more than 20 years and is effective in experimental radiation nephropathy. Captopril may slow the progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms.
Enalapril (Vasotec)
A competitive ACE inhibitor, enalapril reduces angiotensin II levels, decreasing aldosterone secretion. The drug lowers systemic arterial blood pressure, reducing injury caused by elevated blood pressure. It may slow the progression of renal failure by lowering intraglomerular pressure or other intrarenal mechanisms. Enalapril may be used every day or twice per day, which may improve compliance in comparison with a 3-time-per-day medication, such as captopril.
Angiotensin II Receptor Antagonists
Class Summary
ARBs antagonize the action of angiotensin II at the type 1 receptor, reducing systemic arterial blood pressure and blunting the intrarenal effect of angiotensin II. If ACE inhibitors cause cough, ARBs may be substituted.
Losartan (Cozaar)
Losartan is a prototype ARB. It is specific for the type 1, as opposed to type 2, angiotensin receptor. It may induce more complete inhibition of the renin-angiotensin system than do ACE inhibitors. Losartan does not appear to affect bradykinin and is less likely to be associated with cough and angioedema. Use it in patients who are unable to tolerate ACE inhibitors.
Valsartan (Diovan)
Valsartan is a prodrug that directly antagonizes angiotensin II receptors. It displaces angiotensin II from the AT1 receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine release, arginine vasopressin release, water intake, and hypertrophic responses. Valsartan may induce more complete inhibition of the renin-angiotensin system than do ACE inhibitors. It does not affect bradykinin and is less likely to be associated with cough and angioedema. Valsartan is for use in patients who are unable to tolerate ACE inhibitors.
Calcium Channel Blockers
Class Summary
Antihypertensive agents other than or in addition to ACE inhibitors and ARBs may be needed for blood pressure control in many subjects with hypertension and chronic renal failure. The same is true for subjects with radiation nephritis. No evidence indicates that one type of calcium channel blocker is preferred over another for radiation nephritis. However, one should avoid verapamil, because the use of this drug in a subject with hyperkalemia may cause atrial arrest.
Nifedipine (Procardia, Adalat, Nifedical XL)
Like other calcium channel blockers, nifedipine causes peripheral arterial vasodilation by inhibiting calcium influx across vascular smooth-muscle cell membranes. Long-acting formulations are used for control of blood pressure.
Beta Adrenergic Blockers
Class Summary
These agents inhibit chronotropic, inotropic, and vasodilatory responses to beta-adrenergic stimulation
Esmolol (Brevibloc)
An ultra–short-acting beta-1-blocker, esmolol is particularly useful in patients with elevated arterial pressure, especially if surgery is planned. It may be useful as a means to test beta-blocker safety and tolerance in patients with history of obstructive pulmonary disease who are at uncertain risk for bronchospasm from beta-blockade. The elimination half-life of esmolol is 9 min.
Labetalol (Trandate)
Labetalol blocks alpha-1 beta 1-, and beta 2-adrenergic receptor sites, decreasing BP.
Propranolol (Inderal, InnoPran XL)
A class II antiarrhythmic nonselective beta-adrenergic receptor blocker, propranolol has membrane-stabilizing activity and decreases automaticity of contractions. Propranolol is not suitable for emergency treatment of hypertension. Do not administer IV in hypertensive emergencies.
Metoprolol (Lopressor, Toprol-XL)
Metoprolol is a selective beta 1–adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor BP, heart rate, and ECG. When considering conversion from IV to oral (PO) dosage forms, use the ratio of 2.5 mg PO to 1 mg IV metoprolol.
Alkalinizing Agents
Class Summary
Sodium bicarbonate is used as a gastric, systemic, and urinary alkalinizer and has been used in the treatment of acidosis resulting from metabolic and respiratory causes, including, diarrhea, kidney disturbances, and shock. Alternatively, THAM is a buffering agent that increases pH without increasing levels of PaCO2. It may be used to correct metabolic acidosis if sodium bicarbonate is contraindicated.
Sodium bicarbonate
Sodium bicarbonate serves as a buffering agent for metabolic acidosis when significant bicarbonate losses have occurred.
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