eMedicine Specialties > Pediatrics: General Medicine > Nephrology
Chronic Kidney Disease: Treatment & Medication
Updated: Aug 12, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
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Treatment
Medical Care
According to the recommendations of the Pediatric Work Group of KDOQI for chronic kidney disease (CKD), all children with evidence of CKD should be referred to a pediatric nephrologist for consultation and comanagement.4
Patients with chronic kidney disease should be evaluated to determine the following:
- Diagnosis (type of kidney disease)
- Comorbid conditions (such as hyperlipidemia)
- Severity, which based on level of kidney function
- Complications, related to level of kidney function
- Risk for loss of kidney function
- Risk for cardiovascular disease
Treatment of chronic kidney disease should include the following:
- Specific therapy based on diagnosis
- Evaluation and management of reversible causes of renal dysfunction
- Prevention and treatment of complications of decreased kidney function (eg, anemia, bone disease, cardiovascular manifestations, hypertension, growth failure)
- Evaluation and management of comorbid conditions
- Slowing the loss of kidney function
- Preparation for kidney failure therapy
- Replacement of kidney function with dialysis and transplantation if signs and symptoms of uremia are present
- Evaluation of reversible causes of renal dysfunction: Every physician caring for patients with chronic kidney failure must determine the various factors or clinical states that may have aggravated or exacerbated the degree of kidney failure. Once these factors are corrected or reversed, the severity of kidney failure may improve, and kidney function may return to stable basal level of function. The common reversible causes include volume depletion, drugs (nonsteroidal anti-inflammatory drugs (NSAIDs), contrast agents), infection, and congestive heart failure.
- Retarding progression of renal disease: In adults with chronic kidney disease, interventions to slow the progression of kidney disease that have been proven to be effective include strict blood pressure control and ACE inhibitor or angiotensin II receptor–blocker therapy, lipid lowering therapy, and correction of anemia. In these patients, aggressive goals are recommended for both proteinuria and blood pressure. In addition, antihypertensive therapy is used for both renal protection and cardiovascular protection because chronic kidney disease is associated with a marked increase in cardiovascular risk.
- Management of complications
Anemia
The presence of anemia one month after dialysis initiation is associated with an increased risk of prolonged hospitalization and death in pediatric patients. The beneficial effects of treating anemia with erythropoietin in patients who are dialysis-dependent include the improvement of cardiac status, exercise capacity, cognitive function, and quality of life. Recombinant human erythropoietin (rHuEPO) has been used for chronic kidney disease–associated anemia since 1986. Based on the K/DOQI guidelines, the recommended target hemoglobin-to-hematocrit (Hgb/Hct) ratio is 11-12 g/dL/33-36%.11
Iron supplementation is essential to ensure an adequate response to erythropoietin. This is targeted to maintain a transferrin saturation level of 20% or higher and serum ferritin level of 100 ng/dL or higher in children with chronic kidney disease. The pediatric dose of oral iron is 2-3 mg/kg/d divided in 2-3 doses. Oral iron is best absorbed when ingested without food or other medications. The percent of iron absorbed orally is affected by the iron salt form (eg, ferrous sulfate, ferrous gluconate), the amount administered, the dosing regimen, and size of iron stores. Foods that enhance iron absorption include protein from meat and vitamin C. Foods that may inhibit absorption include unrefined grains, soy, coffee, cocoa, herb teas, red wine, calcium, and some proteins (eg, soy, eggs, casein).
Bone disease
Children with stage II chronic kidney disease usually have no signs or symptoms of bone abnormalities. However, these children may have evidence of abnormalities on laboratory testing (eg, decreased serum calcitriol [1,25 dihydroxyvitamin D] and elevated serum parathyroid hormone [PTH]) [3]. This period should be used to counsel the child and family about chronic kidney disease and its impact on bone metabolism. The importance of laboratory monitoring should be emphasized, and future interventions to prevent renal osteodystrophy should be discussed. Subtle signs of renal osteodystrophy begin to be observed when the GFR decreases to 50% of the reference range (stage III disease).
The 2 major types of bone disease commonly encountered in patients with chronic kidney disease prior to maintenance dialysis include enhanced bone resorption (osteitis fibrosa) and osteomalacia/rickets. As chronic kidney disease advances to end-stage renal disease (ESRD), adynamic bone disease may also be found. Mild forms of these derangements in bone metabolism may be observed in the early stages (eg, stage II) and may become more severe as kidney function deteriorates.
Serum concentrations of calcium, phosphate, and PTH should be measured on an ongoing basis in all children with chronic kidney disease, even those with mild disease who often have evidence of abnormalities in bone metabolism. Vitamin D insufficiency and deficiency are very prevalent in pediatric patients across all stages of chronic kidney disease, particularly in nonwhite and obese patients, and may contribute to growth deficits during the earliest stages of chronic kidney disease.12
For calcium and phosphorus measurements, the KDOQI guidelines recommend monthly measurements in stage V disease, whereas PTH measurements should be obtained at least every 3 months.10,4 Early detection of bone metabolic abnormalities ensures that therapeutic interventions can be initiated, thereby preventing or minimizing renal osteodystrophy.
According to the KDOQI clinical practice guidelines for pediatric osteodystrophy, phosphate binders are recommended if phosphorus or intact PTH levels cannot be controlled within the target range despite dietary phosphorus restriction.10,4 Calcium-based phosphate binders are effective in lowering serum phosphorus levels and may be used as the initial binder therapy, but total calcium uptake should be rechecked. The serum levels of corrected total calcium should be maintained within the reference range for the laboratory used. The serum calcium-phosphorus product should be maintained at less than 55 mg2/dL in adolescents.
Serum PTH concentration is inversely correlated with renal function and is almost always elevated when the GFR falls below 60 mL/min per 1.73 m2. Although the optimal serum PTH values in children with chronic kidney disease are uncertain, the KDOQI guidelines recommend targeted levels of serum intact PTH in stage V disease to be 200-300 pg/mL.10,4
Patients with serum levels of intact PTH of more than 300 pg/mL may be treated with active vitamin D sterols to maintain PTH levels at about 2-4 times the reference range.
Cardiovascular manifestations
Cardiovascular disease is the major cause of mortality in both adults and children on long-term dialysis and in adults after kidney transplantation. The prevalence of coronary artery disease (CAD) and left ventricular hypertrophy (LVH), which are precursors of cardiovascular disease mortality and morbidity, is high. The prevalence of congestive heart failure (CHF), which is an independent predictor of death in chronic renal disease, is also high. Strategies should include identification and treatment of modifiable risk factors for cardiovascular disease such as smoking, obesity, hypertension, hyperlipidemia, hypertriglyceridemia, anemia, hypercalcemia, and hyperphosphatemia.
Both hypertension and anemia are associated with LVH in chronic renal disease. Treatment of each condition causes regression of LVH in chronic renal disease.
Homocysteine levels are elevated in chronic kidney disease, and elevated homocysteine levels are associated with cardiovascular disease. The effect of dietary fortification with folic acid on homocysteine levels in chronic kidney disease is unknown.
Elevated levels of total and low-density lipoprotein (LDL) cholesterol are associated with cardiovascular disease in chronic renal disease. The systematic treatment of dyslipidemia in children with chronic renal disease is controversial because conclusive data regarding the risks and benefits are lacking. Hepatic 3-methylglutaryl coenzyme A reductase inhibitors (statins), fibrates, plant stanols, bile acid–binding resins, and dietary manipulation are options for individualized treatment.
Hyperlipidemia
The KDOQI guidelines on dyslipidemias recommend that all children as well as adults with chronic kidney disease should be evaluated for dyslipidemia.10,4 The patients should be evaluated with a complete fasting lipid profile, including total cholesterol, LDL, high-density lipoprotein (HDL), and triglycerides at presentation, and should be evaluated annually thereafter or 2-3 months after a change in treatment or other conditions known to cause dyslipidemia. Elevated levels of total and LDL cholesterol are associated with cardiovascular disease in chronic renal disease.
The National Cholesterol Expert Panel on Children (NCEP-C) treatment guidelines should be followed for children with chronic kidney disease (stages I-IV) and prepubertal children on dialysis. The approach for pubertal children with stage V chronic kidney disease is similar to that for adults, but higher thresholds are used for treating LDL and non-HDL cholesterol. Recommendations for adolescents are discussed in detail elsewhere
Hepatic 3-methylglutaryl coenzyme A reductase inhibitors (statins), fibrates, plant stanols, bile acid–binding resins, and dietary manipulation are options for individualized treatment.
Hypertension
Hypertension is a highly significant and independent predictor for progression of chronic kidney disease in children. The most recent data available (2003) indicate that at least 38% of children with chronic kidney disease in the United States are receiving antihypertensive therapy.13
The optimal target blood pressure for children with chronic renal failure is currently recommended to be below the 90th percentile for age. Treatment of even mild hypertension is important in patients with chronic renal failure to protect against both progressive renal failure and cardiovascular disease, which is markedly increased in even moderate chronic renal disease.
Treatment of hypertension in children, with and without chronic kidney disease, is based on 3 factors: degree of blood pressure elevation, the presence of cardiovascular risk factors, and the presence of end-organ damage. Additionally, the initial antihypertensive agent may be selected based on cause of chronic kidney disease and age.
ACE inhibitors and angiotensin II receptor blockers have an additional benefit in at least some patients with chronic renal disease, slowing the rate of progressive renal injury, independent of the activity of the underlying disease.
Metabolic acidosis
The kidneys play a critical role in acid-base homeostasis by excreting an acid load (produced by cellular metabolism and skeletal growth in children) and preventing bicarbonate loss in the urine. An increasing tendency to retain hydrogen ions has been observed among patients with chronic renal disease, eventually leading to a progressive metabolic acidosis. In children, overt acidosis is characteristically present when the eGFR is less than 30 mL/min per 1.73 m2 (stage IV).
The acidosis in chronic kidney disease in children can be associated with an increased or normal anion gap. Current guidelines recommend maintaining a serum bicarbonate level of 22 mmol/L. If necessary, the authors recommend supplementation with sodium bicarbonate. Sodium bicarbonate therapy is started at 1-2 mEq/kg/d in 2-3 divided doses; the dose is titrated to the clinical target.
Growth
Disruption of the hypothalamic-pituitary growth hormone axis contributes to the growth hormone–resistant state in uremia. Long-term growth hormone treatment in children with chronic kidney disease induces catch-up growth, and most patients may achieve normal adult height if treatment is initiated prior to ESRD.
Based on the current KDOQI guidelines, treatment with recombinant human growth hormone (hGH) should be considered under the following conditions:10,4
- Children whose height for chronological age varies by more than 2 negative standard deviation scores (SDS)
- Children whose height velocity for chronological age varies by more than 2 negative SDS
- Children with growth potential documented by open epiphyses
- No other contraindication for recombinant hGH use
Additionally, the following nutritional and metabolic imbalances should be corrected prior to use of recombinant hGH:
- Insufficient intake of energy, protein, and other nutrients
- Acidosis
- Hyperphosphatemia (correct serum phosphorus level to <1.5 times the upper limit for age)
- Secondary hyperparathyroidism
Surgical Care
Surgical intervention is often recommended in children with obstructive uropathy to relieve acute kidney failure due to initial or recurrent obstruction. These children should be provided follow-up because, despite surgical intervention, they have persistent underlying chronic kidney disease. In those children who opt for hemodialysis, an arteriovenous fistula needs to be created by the vascular surgery team as an access for hemodialysis.
Major clinical predictors to be used for the perioperative management of a patient with chronic renal failure.
Intermediate clinical predictors to be used for the perioperative management of a patient with chronic renal failure.
Minor clinical predictors to be used for the perioperative management of a patient with chronic renal failure.
Diet
Dietary management is of paramount importance in children with chronic kidney disease. These patients have an altered metabolic milieu due to deranged kidney function. The challenge for pediatricians is to optimize the growth and development of children in this setting. The challenge for both pediatricians and dietitians is to make the diet interesting and palatable in order to ensure compliance. The goal is not only to add years to life but also to life to years.
- Energy
- Energy requirement should meet at least recommended dietary allowance (RDA) for normal children of same height age.
- If protein energy malnutrition (PEM) is present, it needs to be increased further to improve weight gain and linear growth. Calorie intake should be enough to enhance the efficiency of protein (protein-sparing effect) and to prevent the patient from lapsing into a catabolic state.
- Poor intake is common in these patients due to anorexia, nausea and dietary restrictions.
- When use of chronological age does not account for the growth, height age should be the basis for energy estimation. Supplementation can be used as per requirement (enteral or parenteral nutrition as needed).
- Protein
- The diet should include 1.1-1.2 g/kg/d protein, with 60-70% protein from high biological value origin.
- Protein is required to maintain positive nitrogen balance for growth and maintain body protein turn over.
- The protein intake must be carefully controlled, avoiding protein malnutrition from an excessively restricted diet while avoiding toxicity from nitrogenous waste products from an excessively generous diet.
- High biological value proteins are of utmost importance because they are beneficial in promoting muscle anabolism and decreasing muscle wasting.
- Protein restriction is not recommended in children because it has not been shown to influence the decrease in renal function in children with chronic kidney disease.
- Phosphorus and calcium
- As the GFR progressively declines, excretion of phosphate decreases, and, hence, serum phosphorus levels increase. Because of this, care must be taken for the following:
- Dietary phosphorus restriction
- Regular phosphate binders with the meals
- The elemental calcium intake recommended for pediatric patients with chronic kidney disease is as follows:
- Age 1-10 years: 500-600 mg/d
- Age 11-18 years: 800-1000 mg/d
- High amounts of phosphorus affects growth in children and, if levels are high over a long period, may cause renal osteodystrophy. Prolonged elevation of serum calcium and phosphorus levels leads to vascular calcification. The daily elemental calcium requirement is about 80-100 mg/kg/d.
- As the GFR progressively declines, excretion of phosphate decreases, and, hence, serum phosphorus levels increase. Because of this, care must be taken for the following:
- Potassium
- The potassium requirement should be individualized depending on the serum potassium levels. Approximately 1600-2400 mg of potassium can be given.
- Close watch should be kept on the potassium levels, and modifications can be made accordingly.
- Hyperkalemia may occur due to excessive intake of high-potassium foods, catabolism, and other causes.
- Special attention should be given if the child is anuric.
- Leaching of pulses and vegetables should be suggested if the child is hyperkalemic.
- Daily bowel movements are important because the GI route accounts for as much as 30% of potassium excretion in patients with chronic renal failure.
- Sodium and fluid
- No added salt (NAS) and restriction of salty snacks is recommended.
- If the child is hypertensive and edematous, further restriction of salt and fluid is emphasized. However, exceptions include diseases in which sodium is lost in the urine (salt-losing nephropathies).
- The allowance of salt depends on the presence of edema, hypertension, and administration of sodium-containing medications. Salt intake should be kept to less than 2400 mg/d.
- Once these children progress to dialysis or opt for kidney transplantation, a dietician should be consulted again because the dietary requirements change.
Medication
Iron salts
These agents 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, Feostat)
Source of iron for hemoglobin synthesis in treating anemia of chronic renal failure. Also used with erythropoietin to prevent iron stores depletion. PO solutions and chewable tabs of ferrous iron salts are available for use in pediatric populations.
Adult
325 mg (60 mg elemental iron) PO qd/tid
Pediatric
2-6 mg/kg/d PO; may administer qd or divided bid
Absorption is enhanced by ascorbic acid; interferes with tetracycline absorption; food and antacids impair absorption
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
GI tract upset; iron toxicity is observed with ingestion of large amount and can be fatal, especially in children
Sodium ferric gluconate complex (Ferrlecit)
Used to treat microcytic hypochromic anemia due to iron deficiency when PO administration is unfeasible or ineffective. Used to replenish iron stores in individuals on erythropoietin therapy who cannot take or tolerate PO iron supplementation.
Adult
125 mg (as elemental iron)/dose IV diluted in 100 mL of 0.9% NaCl solution and infused over at least 1 h with each hemodialysis session; may repeat for a total of 8 doses
Can be administered in combination with erythropoietin
Pediatric
<6 years: Not established
>6 years: 1.5 mg elemental Fe (0.12 mL) per kg IV; dilute in 25 mL 0.9% NaCl and infuse over 1 h for 8 consecutive dialysis sessions; not to exceed 125 mg/session
Alpha tocopherol may decrease stores if administered in combination; coadministration with ACE inhibitors may increase adverse events with IV iron therapy
Documented hypersensitivity; anemias that are not involved with iron deficiency; hemochromatosis; hemolytic anemia; acute phase of infectious kidney disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Contains benzyl alcohol (do not use in neonates); serious hypersensitivity reactions may occur, including first dose; may cause hypotension, malaise, fatigue, weakness, or pain in chest, back, flanks, or groin during administration; monitor Hgb to avoid iron overload
Iron sucrose (Venofer)
Polynuclear iron (III) hydroxide in sucrose for IV use. Contains no preservatives or dextran polysaccharides. Used to treat microcytic hypochromic anemia due to iron deficiency when PO administration is unfeasible or ineffective. Used to replenish iron stores in individuals on erythropoietin therapy who cannot take or tolerate PO iron supplementation.
Adult
100 mg (as elemental iron)/dose undiluted by slow IV injection (20 mg iron/min) or IV infusion (6.7 mg iron/min; diluted in 100 mL of 0.9% NaCl solution) with each hemodialysis session; may repeat for a total of 8 doses; typically requires a minimum cumulative dose of 1000 mg of elemental iron to achieve a favorable hemoglobin or hematocrit response; not to exceed 3 doses per wk
Can be administered in combination with erythropoietin
Pediatric
Not established
Alpha tocopherol may decreased stores if administered in combination; coadministration with ACE inhibitors may increase adverse events with IV iron therapy; decreases bioavailability of PO administered iron
Documented hypersensitivity; anemia unrelated to iron deficiency; hemochromatosis; hemolytic anemia; acute phase of infectious kidney disease
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hypersensitivity reactions have been reported with injectable iron products; may cause hypotension (related to IV administration rate or cumulative dose), cramps, headache, nausea, vomiting, or diarrhea; monitor Hgb to avoid iron overload
Hematopoietic growth factors
These agents are used to stimulate blood cell production. Endogenous erythropoietin stimulates RBC hematopoiesis. Recombinant human erythropoietin (epoetin alfa) and darbepoetin stimulate erythropoiesis in anemic conditions.
Epoetin alfa (Epogen, Procrit)
Stimulates division and differentiation of committed erythroid progenitor cells. Induces release of reticulocytes from bone marrow into blood stream.
Adult
50 U/kg IV/SC 3 times qwk initially; depending on Hct target, may gradually increase dose each mo up to 150 U/kg IV/SC 3 times qwk
Pediatric
<1 month: Not established
>1 month: 50 U/kg IV/SC 1-3 times qwk initially; depending on Hct target, may gradually increase dose each mo up to 250 U/kg 3 times qwk if needed
None reported
Documented hypersensitivity; uncontrolled hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hypertension, history of seizures, or porphyria; decrease dose if Hct increase exceeds 4 U in any 2-wk period or approaching Hct upper target of 36%; caution in iron deficiency or folate/B12 deficiency; do not use multidose vial (contains benzyl alcohol) in premature or young infants; treatment results depend on adequate iron supplementation
Darbepoetin alfa (Aranesp)
Indicated for treatment of hyperphosphatemia secondary to chronic renal failure. Combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces. Calcium acetate 667 mg equivalent to 169-mg elemental calcium.
Stimulates division and differentiation of committed erythroid progenitor cells. Induces release of reticulocytes from bone marrow into blood stream.
Adult
0.45 mcg/kg/wk SC
Pediatric
<11 years: Not established
>11 years (based on European Best Practice Guidelines): 0.45 mcg/kg/wk SC/IV
Coadministration with thalidomide increases thromboembolic risk
Documented hypersensitivity; uncontrolled hypertension
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hypertension, history of seizures, porphyria, liver disease, sickle cell anemia, hypercoagulable disorders, red cell aplasia, or conditions with enhanced thrombotic tendency; decrease dose if Hct increase exceeds 2.5 g/dL in any 4-wk period; complete iron repletion before initiating
Phosphate binders
These 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 possibly also be used for hypocalcemia.
Calcium acetate (Calphron, PhosLo)
Indicated for treatment of hyperphosphatemia secondary to chronic renal failure. Combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces. One cap or tab of calcium acetate 667 mg is equivalent to 169-mg elemental calcium (ie, 1 g calcium acetate equivalent to 250-mg of elemental calcium).
Adult
1334 mg (2 tab/cap) PO tid pc; increase to bring serum phosphate value to 6 mg/dL as long as hypercalcemia does not develop
Pediatric
50-150 mg/kg/d (as elemental calcium) PO divided tid pc for hyperphosphatemia; administer between meals for hypocalcemia
May increase effect of quinidine; may decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; IV administration antagonizes effects of verapamil; large intakes of dietary fiber may decrease calcium absorption and levels
Documented hypersensitivity; hypercalcemia; hypophosphatemia; renal calculi
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypercalcemia or hypercalcuria may occur when therapeutic amounts are administered
Calcium carbonate (Caltrate, Tums)
Used to treat hyperphosphatemia in chronic renal failure. Combines with dietary phosphorus to form insoluble calcium phosphate, which is excreted in feces. Also indicated for hypocalcemia. Calcium carbonate 1 g is equivalent to 400 mg of elemental calcium.
Adult
1-2 g/d PO tid pc; increase dose to lower serum phosphate value to 6 mg/dL as long as hypercalcemia does not develop
Pediatric
50-150 mg/kg/d (as elemental calcium) PO divided tid pc for hyperphosphatemia; administer between meals for hypocalcemia
May decrease effects of tetracyclines, atenolol, salicylates, iron salts, and fluoroquinolones; IV administration antagonizes effects of verapamil; large intakes of dietary fiber may decrease calcium absorption and levels
Renal calculi; hypercalcemia; hypophosphatemia; renal or cardiac disease; digitalis toxicity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypercalcemia or hypercalcuria may occur at therapeutic doses
Sevelamer (Renagel)
Indicated to reduce serum phosphorous in patients with ESRD. Binds dietary phosphate in the intestine, thus inhibiting its absorption. Reduces incidence of hypercalcemic episodes in patients on hemodialysis compared with patients receiving calcium acetate treatment.
Adult
Initial: 800-1600 mg PO tid pc
Maintenance: Increase or decrease by 400-800 mg per meal q2wk to maintain serum phosphorous at 6 mg/dL or less
Pediatric
Not established; limited data suggest 800-1200 mg PO tid pc
May reduce absorption of drugs coadministered with sevelamer; when changes in absorption of PO medications may have clinical consequences (eg, antiseizure or antiarrhythmic drugs), medications should be taken 1 h before or 3 h after a dose of sevelamer
Documented hypersensitivity; bowel obstruction; hypophosphatemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients with dysphagia, severe GI tract motility disorders, or swallowing disorders; does not contain calcium or alkali supplementation (monitor serum calcium, bicarbonate, and chloride levels); may cause or worsen metabolic acidosis with high doses
Vitamin D analogs
Hyperparathyroidism is treated with calcitriol or other active vitamin D analogs. These drugs may also be used to treat hypocalcemia.
Calcitriol (Rocaltrol, Calcijex)
Primary active metabolite of vitamin D-3. Increases calcium levels in serum by promoting absorption of calcium in intestines and retention in kidneys. Decreases excessive serum phosphatase levels and parathyroid levels. Decreases bone resorption.
Should be used in patients with renal failure who are unable to convert the inactive prohormone forms to the active metabolite. Available in PO and parenteral form. Active form of vitamin D. Used in cases of pRTA as multitherapy with large quantities of alkali and potassium supplementation.
Used to suppress parathyroid production and secretion in secondary hyperparathyroidism and for treatment of hypocalcemia in CRF by increasing intestinal calcium absorption.
Adult
0.25 mcg PO qd/qod
0.5 mcg IV qd 3 times qwk
Increase at 4- to 8-wk intervals by 0.25 mcg/d to achieve target PTH level
Pediatric
<3 years: 0.01-0.05 mcg/kg/d PO qd
>3 years: 0.25-0.5 mcg PO qd
Cholestyramine and other bile acid–binding resins decrease absorption; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects
Documented hypersensitivity; hypercalcemia; hyperphosphatemia; hypervitaminosis D; malabsorption syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adequate response in improving hypocalcemia depends on adequate dietary calcium intake; serum calcium phosphate product must not exceed 55 mg/dL to minimize metastatic tissue and blood vessel calcification; avoid hypercalcemia
Paricalcitol (Zemplar)
Formed through the removal of the 19th carbon group and modifications to the side chain of calcitriol, thus reducing the calcemic effect. It has been reported to suppress PTH without significant impact on calcium, phosphorus, or calcium-phosphorus product. Increases calcium levels in serum by promoting absorption of calcium in intestines and retention in kidneys.
Decreases excessive serum phosphatase levels and parathyroid levels. Decreases bone resorption.
Should be used in patients with renal failure who are unable to convert the inactive prohormone forms to the active metabolite. Available in PO and parenteral form. Active form of vitamin D.
Used to suppress parathyroid production and secretion in secondary hyperparathyroidism and for treatment of hypocalcemia in CRF by increasing intestinal calcium absorption.
Adult
Initial dose based on the serum PTH levels:
<500 pg/mL: 1 mcg/d PO
>500 pg/mL: 2 mcg/d PO
Increase at 2- to 4-wk intervals to achieve target PTH level
Pediatric
<5 years: Not established
5-19 years: Data limited; one clinical trial suggests initial dose based on PTH levels:
PTH <500 pg/mL: 0.04 IV 3 times/wk
PTH >500 pg/mL: 0.08 mcg/kg IV 3 times/wk
Adjust dose at 2- to 4-wk intervals based on PTH levels
Cholestyramine and other bile acid-binding resins decrease absorption; magnesium-containing antacids and thiazide diuretics can increase calcitriol effects; do not use phosphate or vitamin D-related compounds concomitantly with paricalcitol; caution if administered with digoxin (digitalis toxicity is potentiated by hypercalcemia)
Documented hypersensitivity; hypercalcemia; hyperphosphatemia; hypervitaminosis D; malabsorption syndrome
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Adequate response to paricalcitol in improving hypocalcemia depends on adequate dietary calcium intake; serum calcium phosphate product must not exceed 55 mg/dL to minimize metastatic tissue and blood vessel calcification; avoid hypercalcemia; caution in breastfeeding; adverse effects include GI tract distress, dry mouth, lightheadedness, edema, chills, or fever
Doxercalciferol (Hectorol)
Vitamin D analog (1-alpha-hydroxyergocalciferol) that does not require activation by kidneys. Requires hydroxylation in liver to be converted to an active vitamin D metabolite. Controls intestinal absorption of dietary calcium, tubular reabsorption of calcium by kidneys, and in conjunction with parathyroid hormone, the mobilization of calcium from skeleton. Indicated for treatment of secondary hyperparathyroidism in ESRD.
Adult
10 mcg PO 3 times/wk at dialysis; adjust dose as needed to lower blood iPTH to 150-300 pg/mL; increase dose by 2.5 mcg/8 wk if iPTH is not lowered by 50% and fails to reach the target range; not to exceed 20 mcg PO 3 times/wk
Alternatively, 4 mcg IV 3 times/wk; may adjust dose by 1-2 mcg/8 wk to maintain iPTH levels
Pediatric
Not established
Cholestyramine and mineral oil may reduce absorption; concurrent use with other vitamin D supplements or magnesium containing antacids (or supplements) may increase toxicity
Documented hypersensitivity; hyperphosphatemia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue other forms of vitamin D before initiating therapy; avoid overdose; monitor calcium levels carefully; hyperphosphatemia may reduce effects; caution in hepatic impairment
Growth hormones
These agents are used pharmacologically as a growth-promoting agent to help optimize growth in developing children with chronic kidney disease (CKD).
Growth hormone (Nutropin, Saizen)
hGH produced by recombinant DNA technology. Results in stimulation of linear growth.
Stimulates erythropoietin, which increases red blood cell mass.
Currently widely available in SC injection form. Adjust dose gradually based on clinical and biochemical responses assessed at monthly intervals, including body weight, waist circumference, serum IGF-1, IGFBP-3, serum glucose, lipids, thyroid function, and whole body dual-energy x-ray absorptiometry. In children, assess response based on height and growth velocity. Continue treatment until final height or epiphysial closure or both have been recorded.
Adult
Not indicated
Pediatric
0.35 mg/kg/wk SC initially, divided into daily or 6 times qwk SC injections
Glucocorticoids may decrease growth-promoting effects
Documented hypersensitivity; closed epiphysis; intracranial lesion; malignancy; acidosis; malnutrition
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May cause injection site pain, lipodystrophy, headache, or intracranial hypertension
Calcimimetic Agent
These agents reduce PTH levels. A small clinical trial by Muscheites et al in children showed an 80% decrease in serum PTH levels.14
Cinacalcet (Sensipar)
Directly lowers iPTH levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease. Indicated for secondary hyperparathyroidism in patients with chronic kidney disease on dialysis.
Adult
30 mg PO qd initially; titrate upward slowly (no more frequent than q2-4wk intervals) by 30 mg increments to target iPTH of 150-300 pg/mL
Take with meals or immediately following; do not crush, chew or cut tablets
Pediatric
Not established, but 0.25 mg/kg PO qd for 4 wk has been shown to lower circulating PTH levels (Muscheites et al, 2008)
Strong CYP450 2D6 inhibitor; may increase serum levels of CYP 2D6 substrates (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants); coadministration with CYP450 3A4 inhibitors (eg, ketoconazole, erythromycin, itraconazole) may decrease cinacalcet clearance
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany; monitor calcium and phosphorus levels closely within 1 wk following initial dose or dose changes, and then monthly (secondary hyperparathyroidism) and q2 mo (parathyroid carcinoma); do not initiate treatment if serum calcium below 8.4 mg/dL; adynamic bone disease may occur if iPTH levels suppressed below 100 pg/mL; caution with hepatic impairment; common adverse effects include nausea and vomiting
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References
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Further Reading
Keywords
chronic kidney disease, CKD, end-stage renal disease, ESRD, end-stage kidney disease, ESKD, chronic renal disease, CRD, chronic renal insufficiency, CRI, adaptive hyperfiltration, end-stage kidney failure, proteinuria, progressive kidney insufficiency, anemia, osteodystrophy, systemic hypertension, intraglomerular hypertension, glomerular hypertrophy, metabolic acidosis, hyperlipidemia, tubulointerstitial disease, systemic inflammation, altered prostanoid metabolism, cardiac arrest, myocardial ischemia, pulmonary edema, hyperkalemia, obstructive uropathy, polydipsia, nocturia, treatment, diagnosis
