eMedicine Specialties > Nephrology > Tubulointerstitial Diseases of the Kidney
Nephrocalcinosis: Treatment & Medication
Updated: Apr 21, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- Treatment of hypercalcemia and hypercalcemic nephropathy
- Adequate hydration by isotonic sodium chloride solution is the single most effective measure to reverse hypercalcemia and protect the kidneys. This may be combined with furosemide to enhance calcium excretion only after clinical euvolemia or mild hypervolemia has been achieved.
- Other treatments include parathyroidectomy or calcium-sensing receptor stimulant cinacalcet (Sensipar), for correction of hyperparathyroidism; chemotherapy, for osteolytic malignancies; steroids, to decrease intestinal calcium absorption and vitamin-D activity; hydroxychloroquine (Plaquenil), for sarcoid granulomas33 ; and calcitonin or bisphosphonates, to inhibit bone resorption.
- Calcium-channel blockers have no role in management.
- Treatment of macroscopic nephrocalcinosis
- Thiazide diuretics and dietary salt restriction will reduce renal calcium excretion in medullary nephrocalcinosis. Potassium and magnesium supplementation will increase the solubility of urinary calcium.
- Citrate supplementation (preferably as potassium citrate) can be used in idiopathic hypercalciuria and in distal RTA, because it increases urinary citrate and decreases urinary calcium excretion.34
- In type 1 hyperoxaluria, treatment with large doses of pyridoxine can lower oxalate production.
- Magnesium supplementation in magnesium-losing nephropathy may be helpful.
- Lessening of nephrocalcinosis may occur over time, especially in idiopathic absorptive hypercalciuria and enteric hyperoxaluria after gastrointestinal bypass surgery. In most other cases, however, such as when it results from primary hyperoxaluria, distal RTA, papillary necrosis, or magnesium-losing nephropathy, nephrocalcinosis is largely irreversible. Therefore, early detection and treatment are important.
Surgical Care
- With copious fluid intake by the patient and the use of pain control, stones passing the midureter and measuring less then 5-7 mm usually pass on their own. Anecdotally, peripheral vasodilators (alpha blockers and calcium-channel blocker antihypertensive agents) are helpful in assisting stone passage.35 Surgery may be required for urinary stones causing obstruction; options include percutaneous nephrolithotomy, laser and shock wave lithotripsy, stent placement, and (rarely) open surgery.
- Parathyroidectomy to remove enlarged adenomas is very helpful in primary hyperparathyroidism and results in a low recurrence rate.
- Attempting to remove calcium nodules from within the renal parenchyma itself has no obvious benefit and causes harm.
Consultations
- Nephrology consultation - Reduced renal function and associated metabolic abnormalities; electrolyte disorders, including metabolic acidosis, hypercalcemia and hypercalciuria; and recurrent nephrolithiasis
- Endocrinology consultation: - hypercalcemia, vitamin-D and phosphate disorders, and sarcoid in association with hypercalcemia.
- Rheumatology consultation - distal RTA associated with rheumatology diseases, such us Sj ö gren's syndrome or system lupus erythematosus.
- Ear-nose-throat or endocrine surgery consultation - For surgical parathyroidectomy (the personal skill and experience of the operating surgeon are important)
Diet
Dietary interventions can be formulated, as part of consultation with an appropriate specialist, only after the underlying metabolic abnormality has been identified.
Medication
The goals of pharmacotherapy are to reduce morbidity and prevent complications.
Diuretic, Thiazide
Thiazide diuretics are extremely helpful in decreasing calcium excretion in several conditions associated with nephrocalcinosis. Hydrochlorothiazide (HCTZ), the most commonly employed thiazide diuretic, is appropriate to use if the serum calcium level is not high; it may correct coincidental high blood pressure.36 The usual dose range is 12.5-25 mg per day, although in rare cases it can reach up to 50 mg per day. However, if HCTZ is used, the dose should be split in 2 to cover a full 24-hour period.
Hydrochlorothiazide (Esidrix, HydroDIURIL, Microzide)
Inhibits reabsorption of sodium in the distal tubules, causing increased excretion of sodium and water, as well as of potassium and hydrogen ions.
Adult
25-50 mg PO divided bid
Pediatric
2-3 mg/kg/d PO divided bid
Decreases effects of anticoagulants, antigout agents, and sulfonylureas; may increase toxicity of allopurinol, anesthetics, antineoplastics, calcium salts, loop diuretics, lithium, diazoxide, digitalis, amphotericin B, and nondepolarizing muscle relaxants
Documented hypersensitivity; anuria; renal decompensation
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 renal disease/failure, hepatic disease, gout, diabetes mellitus, and lupus erythematosus; cross-sensitivity to sulfonamides
Chlorthalidone (Thalitone [US], Apo-Chlorthalidone [Canada])
Inhibits reabsorption of sodium in distal tubules, causing increased excretion of sodium and water as well as potasium and hydrogen ions. Reduces calcium excretion through direct tubular effects.
Adult
12.5 - 25 mg/d PO
Pediatric
1 mg/kg/d PO
May decrease effect of anticoagulants; increases risk of postural hypotension with coadministration of antihypertensives; increases potential for hypokalemia or hypomagnesemia and subsequent cardiotoxicity when coadministered with ACE inhibitors, digoxin, or corticosteroids; antagonizes sulfonylurea effect by decreasing glucose tolerance; increases risk of hyperglycemia when coadministered with diazoxide; increases lithium serum levels; may antagonize effect of antigout medications by causing hyperuricemia; NSAIDs decrease diuretic effect; probenecid increases thiazide levels
Documented hypersensitivity to drug or related diuretics, renal impairment (clearance less than 30% normal), anuria, breast feeding, diabetes mellitus
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal or liver function impairment; may produce electrolyte abnormalities (hypokalemia, hyponatremia); may increase uric acid or serum lipids; hypomagnesemia may occur
Bisphosphonates
These agents are used to treat hypercalcemia and to decrease calcium loss from bone.
Pamidronate (Aredia)
Inhibits bone resorption via actions on osteoclasts or on osteoclast precursors, without significant effects on renal tubular calcium handling. Indicated to treat hypercalcemia.
Adult
Moderate hypercalcemia: 60 mg IV over 4 h initially; alternatively, 90 mg initial single IV infusion over 24 h
Severe hypercalcemia: 90 mg initial IV infusion over 24 h; allow 7 d for retreatment
Pediatric
Not established
None reported
Documented hypersensitivity; hypocalcemia
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
Monitor hypercalcemia-related parameters (ie, serum levels of calcium, phosphate, and magnesium); use vein irritation and thrombophlebitis precautions during IV infusion; hypotension or hypertension may occur with higher doses; caution in patients with CKD or ESRD by significantly reducing the dosage
Calcitonins
Calcitonin is indicated to treat hypercalcemia. It maintains calcium homeostasis by increasing the mineral stores in bone and the renal excretion of calcium. Calcitonin also directly inhibits osteoclastic bone resorption. Because of its longer duration of action, salmon calcitonin is preferred over human calcitonin.
Calcitonin (Miacalcin, Osteocalcin, Cibacalcin, Calcimar)
Lowers elevated serum calcium in patients with multiple myeloma, carcinoma, or primary hyperparathyroidism. Can expect a higher response when serum calcium levels are high. Onset of action is approximately 2 h following injection, and activity lasts for 6-8 h. May lower calcium levels for 5-8 d by about 9% if administered q12h. If administered by the IM route, use multiple injection sites with dose >2 mL.
Adult
Initial dose for hypercalcemia: 4 IU/kg IM/SC q12h; increase dose to 8 IU/kg q12h if response is not satisfactory after 1-2 d and to 8 IU/kg q6h if response remains unsatisfactory >2 d
Pediatric
Not established
May decrease lithium serum levels
Documented hypersensitivity, particularly if sensitive to shellfish.
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
Most common adverse effects include nausea and vomiting, facial flushing, and edema at the site of injection; less common adverse effects include hypocalcemia with tetany and glucose intolerance; perform a skin test prior to initiating salmon calcitonin to assess potential for hypersensitivity; there are reports of autoantibody development in up to 50% of treated individuals, although the treatment remained effective; patients with Paget disease should be routinely evaluated with radiography for osteogenic sarcoma
Vitamins
Pyridoxine (vitamin B-6) deficiency is a known cause of hyperoxaluria. Used to treat nephrocalcinosis, pyridoxine decreases calcium oxalate formation and the subsequent development of kidney stones.
Pyridoxine (Nestrex)
Involved in synthesis of GABA within CNS.
Adult
1 g IV administered slowly; alternatively, 10-20 mg/d for 3 wk; maintain with 1.5-2.5 mg/d PO
Pediatric
5-20 mg/d PO for 3 wk; maintain with 1.5-2.5 mg/d PO
May decrease levodopa effectiveness when used without carbidopa due to enhanced peripheral metabolism; decreases phenytoin and phenobarbital serum levels
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
Seizures have occurred following very high IV doses; long-term administration of high doses may cause neuropathy; safety in pregnancy has not been established for doses exceeding recommended daily allowance
Antimalarial Agent
Hydroxychloroquine can be helpful in controlling hypercalcemia due to sarcoid and is utilized as a glucocorticoid-sparing agent.
Hydroxychloroquine (Plaquenil)
May be most useful in the management of osseous involvement. Inhibits chemotaxis of eosinophils, locomotion of neutrophils, and impairs complement-dependent antigen-antibody reactions.
Adult
200-400 mg PO qd with dose decreased by 50% when response noted
Pediatric
Not established
Serum levels increase with cimetidine; magnesium trisilicate may decrease absorption
Documented hypersensitivity to 4-aminoquinoline derivatives; psoriasis; retinal and visual field changes attributable to 4-aminoquinolines
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 hepatic disease, G-6-PD deficiency, psoriasis, and porphyria; not recommended for long-term use in children; perform periodic ophthalmologic examinations; test for muscle weakness; retinopathy, tinnitus, nerve deafness, skin eruption, headache, anorexia, nausea, vomiting, and diarrhea may occur
Calcimimetic Agent
These can be used in primary hyperparathyroidism to temporarily control hypercalcemia if a patient is a poor surgical risk or if surgery is not immediately available. Experience in such settings is limited.
Cinacalcet (Sensipar)
Directly lowers parathyroid hormone (PTH) 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 hypercalcemia with parathyroid carcinoma.
Adult
30 mg PO qd initially; titrate q2-4wk as needed to normalize calcium levels by sequential doses of 30 mg bid, 60 mg bid, 90 mg bid, and 90 mg tid/qid
Take with meals or immediately after; do not crush, chew or cut tablets
Pediatric
Not established
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
Alkalinizing Agent, Oral
These are used for urinary alkalinization.
Sodium citrate (Bicitra, Oracit)
Treats metabolic acidosis and used as alkalinizing agent where long-term maintenance of an alkaline urine desirable.
Adult
15-30 mL PO of a sodium citrate and citric acid solution containing 500 mg of sodium citrate and 334 mg of citric acid per 5 mL, usually in divided daily doses.
Pediatric
Infants and children: 2-3 mEq/kg/d PO of a sodium citrate and citric acid solution as in adults; usually administered in 2 equal doses.
Decreases therapeutic levels of lithium, chlorpropamide, methotrexate, tetracyclines, and salicylates due to urinary alkalinization; increases toxicity of amphetamines, ephedrine, quinine, and quinidine due to urinary alkalinization
Renal insufficiency and patients on sodium-restricted diet
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
Conversion to bicarbonate may be impaired in hepatic failure and in patients who are in shock or are severely ill.
Potassium citrate (Polycitra-K)
Alkalinizing agent indicated for treatment of systemic metabolic acidosis, urinary alkalinization, or hypocitraturia. Administered PO and metabolized to bicarbonate in the liver.
Each 5 mL of Polycitra contains sodium citrate 500 mg, citric acid 334 mg, and potassium citrate 550 mg (each mL contains 1 mEq potassium, 1 mEq sodium, and 2 mEq bicarbonate).
Adult
15-30 mL PO pc and hs based on tolerance and response
Pediatric
2-15 mEq/kg/d PO divided pc and hs
Distal RTA: 2 mEq/kg/d PO initially; titrate to maintain serum bicarbonate and urinary calcium excretion within the reference range
Hypocitraturia: 5 mEq/kg/d PO initially; adjust to maintain reference range serum bicarbonate and urine citrate
Increased drug effect with potassium-containing medications, potassium-sparing diuretics, ACE inhibitors, or cardiac glycosides (could lead to toxicity); drugs that slow GI transit time (ie, anticholinergics) are expected to increase GI side effects
Documented hypersensitivity; severe renal impairment with oliguria/azotemia; hyperkalemia; untreated Addison disease; acute dehydration
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
Frequent monitoring of serum potassium concentration is recommended; caution in CHF, hypertension, edema, or any condition sensitive to sodium or potassium intake
Conversion of citrate to bicarbonate in the liver may be blocked in severe illness, shock, hepatic failure associated with GI distress; high plasma concentrations of potassium may cause death due to cardiac depression, arrhythmias, or arrest
More on Nephrocalcinosis |
| Overview: Nephrocalcinosis |
| Differential Diagnoses & Workup: Nephrocalcinosis |
 Treatment & Medication: Nephrocalcinosis |
| Follow-up: Nephrocalcinosis |
| Multimedia: Nephrocalcinosis |
| References |
| Further Reading |
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References
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Further Reading
Clinical guidelines:
The American Association of Clinical Endocrinologists and the American Association of Endocrine Surgeons position statement on the diagnosis and management of primary hyperparathyroidism. American Association of Clinical Endocrinologists - Medical Specialty Society
American Association of Endocrine Surgeons - Medical Specialty Society. 2005 Jan-Feb. 6 pages. NGC:004187
Clinical trials:
Alkaline Citrate Treatment to Lower the Risk of Nephrocalcinosis in Preterm Infants
International Registry for Primary Hyperoxaluria
Randall's Plaque Study: Pathogenesis and Relationship to Nephrolithiasis
Treatment of Hypoparathyroidism With Synthetic Human Parathyroid Hormone 1-34
Keywords
nephrocalcinosis, kidney, kidneys, kidney stones, kidney stone, hypercalcemia, hypercalciuria, hyperparathyroidism, nephrolithiasis, urinary stones, urinary stone, medullary nephrocalcinosis, crystal-induced nephropathy, increase in renal calcium content, microscopic nephrocalcinosis, macroscopic nephrocalcinosis, hypercalcemic nephropathy
