Medullary Nephrocalcinosis

Medullary nephrocalcinosis is deposition of calcium salts (calcium phosphate or oxalate) in the renal medulla and papillae, and the commonest type of nephrocalcinosis.

• Causes: medullary sponge kidney (about 20 percent), distal renal tubular acidosis (the commonest cause in adults and children), primary hyperparathyroidism, hypercalcaemia of any cause (sarcoidosis, vitamin D toxicity, milk-alkali syndrome, malignancy), hyperoxaluria, hypercalciuria (idiopathic, Bartter and Dent syndromes), loop diuretics in preterm infants, hypomagnesaemia, hypophosphatasia, Lowe syndrome, renal tuberculosis, papillary necrosis, hypokalaemia, acetazolamide, amphotericin and long term high dose vitamin D or calcium.
• Risk factors for stones and obstruction: alkaline urine, low urinary citrate, high urinary calcium, dehydration.

Often asymptomatic; found on imaging.

• Stones with renal colic, haematuria, recurrent urinary tract infection, polyuria and nocturia (concentrating defect), hypokalaemic weakness (renal tubular acidosis), rickets or osteomalacia, growth failure, deafness.
• Hypercalcaemia features: polyuria, constipation, abdominal pain, depression; primary hyperparathyroidism: bone pain, peptic ulcer, pancreatitis.
• Differential diagnosis: cortical nephrocalcinosis (acute cortical necrosis, chronic glomerulonephritis, oxalosis), papillary necrosis, renal tuberculosis, nephrolithiasis, tumour calcification, vascular calcification.
• Complications: nephrolithiasis, chronic kidney disease (progressive in many), urinary tract infection, tubular dysfunction, hypertension, bone disease, end stage kidney disease.

Ultrasound shows hyperechoic medullary pyramids (with or without shadowing); CT detects calcifications in the papillae and pyramids with high sensitivity and shows the "bouquet" in medullary sponge kidney; plain radiographs show calcified pyramids.

• Cause work-up: serum calcium (corrected), phosphate, magnesium, parathyroid hormone, 25-hydroxy vitamin D, bicarbonate, potassium, chloride, creatinine, urate, alkaline phosphatase.
• Urine: pH (persistently above 5.5 in renal tubular acidosis), culture, 24-hour calcium, citrate, oxalate, urate, magnesium; ammonium chloride loading test (0.1 g/kg orally) or furosemide-fludrocortisone test for incomplete distal renal tubular acidosis.
• Intravenous urography or CT urography shows contrast pooling in dilated collecting ducts (medullary sponge kidney); genetic testing for hereditary tubulopathies; chest radiograph and angiotensin converting enzyme for sarcoidosis.

Supportive: fluids to urine output above 2.5 L daily, sodium below 2 g daily, normal dietary calcium (1000 mg daily; avoid supplements), avoid vitamin D excess, correct causes (stop loop diuretics, acetazolamide, high dose vitamin C).

Pharmacological (by cause):

• Distal renal tubular acidosis: alkali replacement with potassium citrate 1 to 2 mmol/kg/day in 3 to 4 divided doses, or sodium bicarbonate 1 to 2 mmol/kg/day, aiming for serum bicarbonate 22 mmol/L or above; potassium replacement; children need higher doses (2 to 4 mmol/kg/day); vitamin D and phosphate if rickets (with specialist advice).
• Idiopathic hypercalciuria and medullary sponge kidney: hydrochlorothiazide 25 mg twice daily (children 1 mg/kg/day) or indapamide 2.5 mg daily; potassium citrate 30 to 60 mmol daily for hypocitraturia.
• Primary hyperparathyroidism: parathyroidectomy; cinacalcet 30 mg daily increasing to 60 to 90 mg if not fit for surgery.
• Hypercalcaemia: hydration, bisphosphonate (zoledronic acid 4 mg IV), and for sarcoidosis prednisolone 20 to 40 mg daily; milk-alkali: stop calcium and antacids.
• Hyperoxaluria: low oxalate diet, calcium with meals, pyridoxine 100 to 200 mg daily.
• Renal tuberculosis: full anti-tuberculosis therapy chosen by susceptibility results.
• Infection: culture directed antibiotics; stone colic management with analgesia (diclofenac 75 mg IM or paracetamol 1 g IV).

Procedures: lithotripsy, ureteroscopy or percutaneous nephrolithotomy for stones; parathyroidectomy; no direct treatment of established calcification.

Special groups: preterm infants (stop furosemide, give hydrochlorothiazide 1 mg/kg/day if needed; resolves over months), children with renal tubular acidosis (growth monitoring), pregnancy (hydration, avoid thiazides in the first trimester if possible).

Red flags: obstructing stone with infection, rising creatinine, severe hypokalaemia with paralysis, hypercalcaemia above 3.0 mmol/L.

Follow-up: serum bicarbonate, potassium, calcium and creatinine every 3 to 6 months; 24-hour urine at 8 to 12 weeks after treatment changes; ultrasound or CT yearly for stones and calcification; renal tubular acidosis treated lifelong.