Doctor123.org

Nephrocalcinosis

Doctor123.org

Nephrocalcinosis

BASICS

DESCRIPTION

Stone analysis in case of concurrent nephrolithiasis ‚

Thiazide diuretics are the drug of choice for hypertension; caution in renal impairment ‚

Oral Oxalobacter formigenes degrades oxalate in the gastrointestinal tract. Supplementation in patients with hyperoxaluria appears promising and safe (5)[C]. ‚

Oral barley, lemon juice with honey, and tea infused with lady 's mantle have been used for NC treatment but lack sufficient evidence on effectiveness and safety in humans. ‚

Admission Criteria/Initial Stabilization

Normal saline solution to reverse severe hypercalcemia and restore circulatory volume ‚

Kidney function, blood pressure, and electrolytes stable to be managed as an outpatient ‚

11 Vervaet ‚ BA, Verhulst ‚ A, D 'Haese ‚ PC, et al. Nephrocalcinosis: new insights into mechanisms and consequences. Nephrol Dial Transplant. 2009; 24(7):2030 " “2035.22 Hoppe ‚ B, Kemper ‚ MJ. Diagnostic examination of the child with urolithiasis or nephrocalcinosis. Pediatr Nephrol. 2010;25(3):403 " “413.33 Schell-Feith ‚ EA, Kist-van Holthe ‚ JE, van der Heijden ‚ AJ. Nephrocalcinosis in preterm neonates. Pediatr Nephrol. 2010;25(2):221 " “230.44 Edvardsson ‚ V, Goldfarb ‚ DS, Lieske ‚ JC, et al. Hereditary causes of kidney stones and chronic kidney disease. Pediatr Nephrol. 2013;28(10):1923 " “1942.55 Habbig ‚ S, Beck ‚ BB, Hoppe ‚ B. Nephrocalcinosis and urolithiasis in children. Kidney Int. 2011;80(12):1278 " “1291.

National Institutes of Health. Nephrocalcinosis. http://rarediseases.info.nih.gov/gard/7177/nephrocalcinosis/resources/1. Accessed 2014. ‚

  • Nephrocalcinosis (NC) is a condition where calcium salt deposits form in the renal parenchyma.
  • NC is related but distinct from nephrolithiasis, where deposits form in the renal collecting system (1).
  • Although primarily considered a radiographic diagnosis and often discovered incidentally on radiographic imaging, NC can portend more serious kidney and systemic disease (2).
  • Range of symptoms: asymptomatic to vague, nonspecific findings or symptoms related to underlying cause of hypercalcemia
  • Descriptive types of NC based on radiographic location (2):Medullary type: most commonly related to metabolic disorders; the most common type of NC (95%)Cortical type: most commonly associated with renal tubular acidosis and necrosisDiffuseMicroscopic: noted only on histologic examination of renal tissue
  • Medullary type: most commonly related to metabolic disorders; the most common type of NC (95%)
  • Cortical type: most commonly associated with renal tubular acidosis and necrosis
  • Diffuse
  • Microscopic: noted only on histologic examination of renal tissue

EPIDEMIOLOGY

  • 7 " “41% of preterm newborns (3)
  • Up to 20% of patients with hyperparathyroidism

ETIOLOGY AND PATHOPHYSIOLOGY

  • Intratubular NC: crystal adherence to damaged tubular epithelium leading to translocation or obstruction
  • Interstitial NC: plaque formation in the ascending loops of Henle and invade the medullary interstitium (4)
  • Increased prevalence of NC with certain hereditary disorders:Dent diseaseFamilial hypomagnesemia with hypercalciuria and nephrocalcinosisPrimary hyperoxaluriaBartter syndromeLiddle syndrome (5)
  • Dent disease
  • Familial hypomagnesemia with hypercalciuria and nephrocalcinosis
  • Primary hyperoxaluria
  • Bartter syndrome
  • Liddle syndrome (5)

RISK FACTORS

  • MedullaryPrimary hyperparathyroidismRenal tubular acidosisPrematurityHereditary disordersHyperthyroidismGranulomatous diseases such as sarcoidosisOversupplementation of phosphate and vitamin DMultiple myelomaCushing syndromeChronic steroid useMetastatic neoplasmMedullary sponge kidneyMilk-alkali syndromeHyperuricemiaSickle cell disease
  • CorticalRenal infarct, ischemia, or toxinsHyperoxaluriaChronic glomerulonephritisAlport syndromeAutosomal recessive polycystic kidney diseaseOpportunistic intrarenal infections such as Mycobacterium avium or Pneumocystis carinii pneumonia.
  • Primary hyperparathyroidism
  • Renal tubular acidosis
  • Prematurity
  • Hereditary disorders
  • Hyperthyroidism
  • Granulomatous diseases such as sarcoidosis
  • Oversupplementation of phosphate and vitamin D
  • Multiple myeloma
  • Cushing syndrome
  • Chronic steroid use
  • Metastatic neoplasm
  • Medullary sponge kidney
  • Milk-alkali syndrome
  • Hyperuricemia
  • Sickle cell disease
  • Renal infarct, ischemia, or toxins
  • Hyperoxaluria
  • Chronic glomerulonephritis
  • Alport syndrome
  • Autosomal recessive polycystic kidney disease
  • Opportunistic intrarenal infections such as Mycobacterium avium or Pneumocystis carinii pneumonia.

GENERAL PREVENTION

COMMONLY ASSOCIATED CONDITIONS

  • Hypercalcemia
  • Hypercalciuria
  • Renal tubular acidosis
  • Hyperoxaluria
  • Urinary stasis
  • Hyperparathyroidism
  • Treatment of hypoparathyroidism
  • Medullary sponge kidney
  • Osteoporosis

DIAGNOSIS

HISTORY

  • Preterm birth
  • Personal or family history of nephrolithiasis or heritable kidney disease
  • Polyuria and polydipsia
  • Hematuria

PHYSICAL EXAM

  • Often nonspecific
  • Blood pressure
  • Abdominal exam: may find nonspecific abdominal tenderness related to hypercalcemia or specific tenderness if coexisting symptomatic nephrolithiasis (2)
  • Flank exam: may have costovertebral angle tenderness in the presence of coexisting nephrolithiasis or renal infection

DIFFERENTIAL DIAGNOSIS

  • Nephrolithiasis
  • Urinary tract infection
  • Diabetes
  • Atherosclerotic kidney disease
  • Renal tuberculosis

DIAGNOSTIC TESTS & INTERPRETATION

  • Lab: comprehensive metabolic profile; urinalysis with culture; spot urine testing for calcium, oxalate, citrate, magnesium, and uric acid
  • Imaging: KUB or US; in adults, consider confirmation with noncontrast CT. (2)
  • PTH, vitamin D, plasma oxalates, acid " “base status
  • In older children and adults: 24-hour urine testing for calcium, citrate, uric acid, magnesium, phosphate, cystine, protein, and oxalate
  • Genetic counseling and genetic testing if inherited metabolic disorder is possible

TREATMENT

GENERAL MEASURES

  • Manage or prevent hypercalcemia.
  • Address hyperparathyroidism or other underlying cause.
  • In setting of preserved renal function, decrease solute concentration in the urine by maintaining a high-fluid intake across the length of the day. In children, the target daily oral intake of fluid should be >1.5 to 2 L per 1.73 m2 body surface area (5)[C].

MEDICATION

  • For hypercalcemic etiologies in adults:HyperparathyroidismCinacalcet: Start at 30 mg PO BID with food, and then increase every 2 to 4 weeks by an additional 30 mg per dose up to 90 mg PO BID; then may increase to a maximum of 90 mg PO TID " “QID. Dose is titrated to normal serum calcium levels.Malignancies: appropriate chemotherapySarcoid granulomasHydroxychloroquine: 400 mg PO QD " “BID with food; may decrease dose to 200 mg PO QD " “BID if intolerable gastrointestinal effectsHeightened bone resorptionCalcitonin-salmon: 4 U/kg IM/SC q12h; increase by 8 U q12h PRN. Dose is titrated to normal serum calcium levels.Bisphosphonates
  • For hypercalcemia in children:Severe hypercalciuriaHydrochlorothiazide: 0.5 to 1 mg/kg PO daily dose divided BID (5)[C]Crystallization inhibition: Citrate supplementation increases calcium oxalate, cysteine, and uric acid solubility, but pH should be monitored, as higher levels (>7.0) may cause calcium phosphate stone formation (4)[C].For infectious etiologies, determine the appropriate antibiotic.
  • HyperparathyroidismCinacalcet: Start at 30 mg PO BID with food, and then increase every 2 to 4 weeks by an additional 30 mg per dose up to 90 mg PO BID; then may increase to a maximum of 90 mg PO TID " “QID. Dose is titrated to normal serum calcium levels.
  • Malignancies: appropriate chemotherapy
  • Sarcoid granulomasHydroxychloroquine: 400 mg PO QD " “BID with food; may decrease dose to 200 mg PO QD " “BID if intolerable gastrointestinal effects
  • Heightened bone resorptionCalcitonin-salmon: 4 U/kg IM/SC q12h; increase by 8 U q12h PRN. Dose is titrated to normal serum calcium levels.Bisphosphonates
  • Cinacalcet: Start at 30 mg PO BID with food, and then increase every 2 to 4 weeks by an additional 30 mg per dose up to 90 mg PO BID; then may increase to a maximum of 90 mg PO TID " “QID. Dose is titrated to normal serum calcium levels.
  • Hydroxychloroquine: 400 mg PO QD " “BID with food; may decrease dose to 200 mg PO QD " “BID if intolerable gastrointestinal effects
  • Calcitonin-salmon: 4 U/kg IM/SC q12h; increase by 8 U q12h PRN. Dose is titrated to normal serum calcium levels.
  • Bisphosphonates
  • Severe hypercalciuriaHydrochlorothiazide: 0.5 to 1 mg/kg PO daily dose divided BID (5)[C]
  • Crystallization inhibition: Citrate supplementation increases calcium oxalate, cysteine, and uric acid solubility, but pH should be monitored, as higher levels (>7.0) may cause calcium phosphate stone formation (4)[C].
  • For infectious etiologies, determine the appropriate antibiotic.
  • Hydrochlorothiazide: 0.5 to 1 mg/kg PO daily dose divided BID (5)[C]

ISSUES FOR REFERRAL

  • Nephrologist should be considered in any patient with a hereditary disorder leading to NC or any patient with worsening renal insufficiency or failure.
  • Genetic counseling should be considered for any pediatric patient with NC, especially if not a premature infant.
  • Dietitian input, from simply counseling patients on a low-sodium diet to formulating a special diet in patients suffering from an underlying metabolic disorder
  • Infectious disease specialist in the case of renal infection or opportunistic renal infection (in HIV-positive patients)

ADDITIONAL THERAPIES

SURGERY/OTHER PROCEDURES

  • Parathyroidectomy for primary hyperparathyroidism related to a hyperfunctioning adenoma
  • Renal transplant for patients in end-stage renal failure (4)[C]
  • Combined liver " “kidney transplant in patients diagnosed with primary hyperoxaluria type 1 due to defective enzyme that is liver-specific (5)[C]

COMPLEMENTARY & ALTERNATIVE MEDICINE

INPATIENT CONSIDERATIONS

  • Hypercalcemia: rarely occurs with NC but could be a medical emergency
  • Renal failure: Early, aggressive management is the key for best long-term prognosis.
  • Maintain vigilance for signs and symptoms of hypercalcemia such as abdominal pain, bone pain, weakness, and confusion.
  • Remain attentive to renal function as demonstrated by urine output, fluid intake, and serial renal laboratories.
  • Observe for hypertension with serial blood pressure monitoring.

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

  • Based on etiology
  • Patients often need ongoing trending of serum calcium, phosphate, uric acid, and renal function.

DIET

PATIENT EDUCATION

PROGNOSIS

  • Depends on etiology
  • Best prognosis with idiopathic hypercalciuria and reversible disease; worse prognosis with type 1 hyperoxaluria and other inherited metabolic disorders
  • Majority of NC in premature neonates resolves (3)[C].
  • Primary concern in medullary NC is renal failure.
  • Once detected, initial treatment of NC should be focused on potentially reversible etiologies (e.g., infection) and then preventing or treating renal insufficiency.

COMPLICATIONS

REFERENCES

ADDITIONAL READING

CODES

ICD10

  • E83.59 Other disorders of calcium metabolism
  • N29 Oth disorders of kidney and ureter in diseases classd elswhr

ICD9

SNOMED

  • nephrocalcinosis (disorder)
  • Medullary nephrocalcinosis (disorder)
  • Cortical nephrocalcinosis (disorder)
  • Neonatal nephrocalcinosis (disorder)

CLINICAL PEARLS

  • Nephrocalcinosis is often found incidentally upon imaging.
  • Nephrocalcinosis should be considered a sign of another disease process, more than it should be considered a disease process itself (5).
  • Nephrocalcinosis is most common in premature infants receiving neonatal intensive care unit care (pediatric population) and in adults who suffer from hyperparathyroidism.
  • Rarely, nephrocalcinosis is associated with inherited metabolic disorders.