Nephrocalcinosis

Nephrocalcinosis refers to increased calcium content of the kidneys. Nephrocalcinosis usually applies to a generalised increase in renal calcium content rather than the localised increase seen in calcified renal infarction and renal tuberculosis.¹

Nephrocalcinosis can be divided into 3 categories (there is invariably a degree of overlap between the categories):¹

• Chemical nephrocalcinosis: 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 nephrocalcinosis: calcium precipitates in crystalline form as oxalate and/or phosphate, but it is only seen with the aid of a microscope.
• Macroscopic nephrocalcinosis: large areas of calcification can be seen.

Nephrocalcinosis may be associated with renal calculi but is more likely to represent an underlying metabolic disorder. It can also be differentiated into:

• Medullary nephrocalcinosis:
  • is the most frequent form and is characterised by the exclusive involvement of the medullary pyramids
  • is usually associated with disordered calcium homeostasis
• Cortical nephrocalcinosis:
  • rarer and involves all the renal parenchyma
  • frequently associated with severe metabolic defects, such as primary hyperoxaluria or end-stage renal failure
  • the most frequent causes are chronic glomerulonephritis and acute cortical necrosis
  • other causes include haemolytic uraemic syndrome, chronic pyelonephritis, vesicoureteral reflux, renal transplantation and polycystic kidney disease

Microscopic nephrocalcinosis is a common incidental finding at post-mortem, but macroscopic nephrocalcinosis is uncommon.

Medullary nephrocalcinosis

• Hypercalcaemia: for example, diet, hyperparathyroidism, vitamin D excess, bone metastases, bone loss from chronic immobilisation and severe osteoporosis, sarcoidosis, idiopathic hypercalcaemia of infancy (Williams' disease).
• Hypercalciuria:
  • Altered renal tubular handling, e.g. idiopathic hypercalciuria, distal renal tubular acidosis (is associated with low urinary excretion of citrate), hypothyroidism, inherited tubular disorders (e.g. Bartter's syndrome and familial magnesium-losing nephropathy), and may follow intensive loop diuretic treatment in premature infants.
  • Hypercalciuria is also a feature of Fanconi's syndrome and proximal renal tubular acidosis, but these conditions are less commonly associated with nephrocalcinosis.
• Absence of factors in urine (e.g. citrate) that help to maintain calcium salts in solution, e.g. in conditions causing chronic hypokalaemia, e.g. primary hyperaldosteronism.
• Medullary sponge kidney.²

Cortical nephrocalcinosis

• Acute renal cortical necrosis: causes include infection, extracorporeal shock wave lithotripsy, haemolytic uraemic syndrome.
• Primary and secondary oxalosis.
• Chronic glomerulonephritis.
• Intrarenal infections in HIV-seropositive patients.
• Chronic pyelonephritis.
• Renal graft rejection.
• Autosomal recessive polycystic disease.

• The underlying aetiology primarily determines the presentation of nephrocalcinosis, although in most cases it is asymptomatic and is identified as an abnormality on imaging of the renal tract.
• Presentation can range from incidental detection on abdominal X-rays or ultrasounds performed for another reason, to life-threatening.
• Hypercalcaemia: polyuria and polydipsia, nausea and vomiting.
• In medullary nephrocalcinosis, calcium nodules commonly rupture into the calyceal system to form urinary stones and cause renal colic, haematuria, urinary tract infections or the passage of urinary stones.
• May rarely present with features of acute renal failure or chronic renal failure.

• Serum calcium, phosphate, albumin: to establish presence of hypercalcaemia.
• Serum electrolytes and assessment of renal function.
• Urinalysis with microscopy and culture: evidence of urinary tract infection.
• Twenty-four hour urinary excretion of calcium, oxalate, citrate, and protein: assessment of hypercalciuria and possible nephrotic syndrome.
• Parathyroid hormone levels.
• Thyroid-stimulating hormone.
• Urinary magnesium: magnesium-losing nephropathy.
• Abdominal X-rays: detection of nephrocalcinosis, urinary stones.
• Ultrasound: more sensitive than conventional radiography.
• CT scan is more effective in detecting calcification and can be used to differentiate medullary and cortical deposition.
• Renal biopsy: may be required in the assessment of the underlying cause.

Nephrocalcinosis and urinary calculi may co-exist.

• Ensure adequate fluid intake.
• Treatment of the underlying condition, e.g. parathyroidectomy to control a hyperfunctioning parathyroid gland.
• Early treatment of reversible causes of renal failure, such as treatment of urinary infections, calculous obstruction, and hypertension, is essential.
• Once renal failure is established, it must be treated accordingly.
• Surgical intervention may be required for significant stone formation in the renal tract, especially if causing obstruction or infection.
• Lithotripsy may cause renal damage, as the calcium deposition is largely parenchymal.

May lead to uncontrolled hypertension, renal infection, scarring, renal colic, defects of renal tubular function and renal failure.

The prognosis depends mainly on the aetiology of the nephrocalcinosis.