Nephrocalcinosis

Nephrocalcinosis refers to generalized calcium deposition in the kidney and does not include the focal calcium deposition associated with focal renal injury. It is caused by diseases that cause hypercalcemia, hyperphosphatemia, hypercalciuria, hyperphosphaturia, and hyperoxaluria. The result is patchy atrophy and calcification of the kidney.

It can be divided into three categories: (1)

• Chemical: increased concentration of calcium in renal cells, especially the tubular epithelium, causing adverse effects on renal structure and function - e.g. increased excretion of water, sodium, potassium, calcium and magnesium.
• Microscopic: calcium precipitates in crystalline form as oxalate and/or phosphate.
• Macroscopic: large areas of calcification can be seen.

1. Conditions causing both hypercalcemia and hypercalciuria

• Primary hyperparathyroidism
• Vitamin D therapy
• Sarcoidosis
• Milk-alkali syndrome
• Congenital hypothyroidism

2. Conditions causing hypercalciuria without hypercalcemia

• Distal renal tubular acidosis
• Medullary sponge kidney
• Neonatal nephrocalcinosis and loop diuretics
• Inherited tubulopathies
• Chronic hypokalaemia
• Beta thalassemia

3. Conditions causing Hyper-phosphaturia and hyperphosphatemia

• Tumour lysis syndrome
• Oral sodium phosphate bowel preparations

4. Conditions causing Hyper-phosphaturia without hyperphosphatemia

• Inherited tubulopathies such as Dent disease, Lowe syndrome
• X-linked, autosomal dominant, and autosomal recessive hypophosphatemic rickets.

Investigations:(1)

• blood tests - Serum calcium, phosphate, albumin, renal function, parathyroid hormone levels, TSH.
• urine tests - haematuria, proteinuria, pyuria, hypercalciuria, urinary magnesium
• abdominal X-ray - may reveal renal calculi or nephrocalcinosis
• ultrasound: more sensitive than conventional radiography and can be superior to CT scan in some clinical scenarios (eg, nephrocalcinosis associated with hypoparathyroidism). (2)
• CT scan: more effective in detecting calcification and can be used to differentiate medullary and cortical deposition.

Treatment is directed to treat the underlying cause of nephrocalcinosis. Strategies to reduce the urinary concentration of calcium, phosphate, or oxalate are used. Fluid intake is increased to produce at least 2 litres of urine a day. (3)

Among patients with hypercalciuria, urinary calcium excretion can be reduced by restricting the amount of animal protein, decreasing the sodium intake to less than 100 milliequivalents /day, increasing the potassium intake, and using a thiazide diuretic to reduce the urinary calcium excretion. However, patients with hypercalcemia should not use a thiazide diuretic.

In nephrocalcinosis due to distal renal tubular acidosis, potassium citrate is used in patients with hypocitraturia and pH less than 7. This not only replenishes the potassium loss but also achieves a normal urinary citrate level, thereby increasing the solubility of calcium.

References:

1. Oliveira B, Kleta R, Bockenhauer D, et al; Genetic, pathophysiological, and clinical aspects of nephrocalcinosis. Am J Physiol Renal Physiol. 2016 Dec 1;311(6):F1243-F1252.
2. Boyce AM et al. Ultrasound is superior to computed tomography for assessment of medullary nephrocalcinosis in hypoparathyroidism. J Clin Endocrinol Metab. 2013 Mar;98(3):989-94.
3. Gambaro G, Trinchieri A; Recent advances in managing and understanding nephrolithiasis/nephrocalcinosis. F1000Res. 2016 Apr 18;5:F1000 Faculty Rev-695