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Nephrocalcinosis

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find one of our health articles more useful.

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What is nephrocalcinosis?1 2 3

Nephrocalcinosis is defined as generalised deposition of calcium phosphate and/or calcium oxalate in the kidney, predominantly in the interstitium. Calcifications in renal pyramids, characteristic of medullary nephrocalcinosis, are seen in 98% of nephrocalcinosis patients.

Clinical presentation and course are not dependent on the severity of nephrocalcinosis. The critical feature in nephrocalcinosis is hypercalciuria with or without hypercalcaemia.

Nephrocalcinosis is closely associated with renal stone formation (urolithiasis) resulting from increased urinary calcium levels (hypercalciuria).4

Advances in uroendoscopy have led to a further definition: the radiographic demonstration of diffuse, fine renal parenchymal calcifications.5

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

  • Chemical nephrocalcinosis: increased concentration of calcium in renal cells, especially the tubular epithelium, causing adverse effects on renal structure and function - eg, increased excretion of water, sodium, potassium, calcium and magnesium.

  • Microscopic nephrocalcinosis: calcium precipitates in crystalline form as oxalate and/or phosphate; however, 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:

    • The most frequent form, characterised by the exclusive involvement of the medullary pyramids.

    • It is usually associated with disordered calcium homeostasis.

  • Cortical nephrocalcinosis:

    • Rarer and involving all the renal parenchyma.

    • Frequently associated with severe metabolic defects, such as primary hyperoxaluria or end-stage kidney disease.

    • 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.

Nephrocalcinosis epidemiology

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

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What causes nephrocalcinosis? (Aetiology)2

Medullary nephrocalcinosis

Cortical nephrocalcinosis

Nephrocalcinosis symptoms (presentation)2

  • 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.

  • May cause hypertension.

  • 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 kidney injury or chronic kidney disease.

Presenting symptoms in children include failure to thrive in the first year of life, urinary tract infections, bladder voiding dysfunction or abdominal pain, and psychomotor delay.7

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Investigations2

Blood tests

  • Serum calcium, phosphate, albumin: to establish the presence of hypercalcaemia.

  • Serum electrolytes and assessment of renal function.

  • Parathyroid hormone levels.

  • Thyroid-stimulating hormone (TSH) levels.

Urine investigations

  • Urinalysis with microscopy and culture: evidence of urinary tract infection.

  • 24-hour urinary excretion of calcium, oxalate, citrate and protein: assessment of hypercalciuria and possible nephrotic syndrome.

  • Urinary magnesium: magnesium-losing nephropathy.

Radiology

  • Abdominal X-rays: detection of nephrocalcinosis, urinary stones.

  • Ultrasound: more sensitive than conventional radiography and can be superior to CT scan in some clinical scenarios (eg, nephrocalcinosis associated with hypoparathyroidism).8

  • CT scan: more effective in detecting calcification and can be used to differentiate medullary and cortical deposition.

Endoscopy
When calcification in close association with the renal papillae is seen on CT scans, distinguishing nephrolithiasis from nephrocalcinosis may require direct visual inspection using endoscopy.5

Renal biopsy
May be required in the assessment of the underlying cause.

Genetic testing
May play an increasing role in nephrocalcinosis presenting in children in the future.9

Associated diseases

Nephrocalcinosis and urinary calculi may co-exist. Nephrocalcinosis and calcium nephrolithiasis are considered as two independent pathologies.10

Common associated conditions include:

Rarer associated conditions include:

Nephrocalcinosis treatment and management11

See also separate Hypercalcaemia article.

  • Ensure adequate fluid intake.

  • Treatment of the underlying condition - eg, 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. See separate Acute Kidney Injury and Chronic Kidney Disease articles.

  • 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.

Complications11

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

Prognosis

The prognosis depends mainly on the aetiology of the nephrocalcinosis.

Early diagnosis and treatment of the underlying condition in children is associated with catch-up growth and stabilisation of glomerular function in many children but not with the reduction in the degree of nephrocalcinosis in the majority of cases.7

Further reading and references

  1. Shavit L, Jaeger P, Unwin RJ; What is nephrocalcinosis? Kidney Int. 2015 Jul;88(1):35-43. doi: 10.1038/ki.2015.76. Epub 2015 Mar 25.
  2. 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. doi: 10.1152/ajprenal.00211.2016. Epub 2016 Sep 7.
  3. Kumbar L, Yee J; Nephrocalcinosis: A Diagnostic Conundrum. Am J Kidney Dis. 2018 Apr;71(4):A12-A14. doi: 10.1053/j.ajkd.2017.11.025.
  4. Dickson FJ, Sayer JA; Nephrocalcinosis: A Review of Monogenic Causes and Insights They Provide into This Heterogeneous Condition. Int J Mol Sci. 2020 Jan 6;21(1):369. doi: 10.3390/ijms21010369.
  5. Miller NL, Humphreys MR, Coe FL, et al; Nephrocalcinosis: re-defined in the era of endourology. Urol Res. 2010 Dec;38(6):421-7. Epub 2010 Nov 6.
  6. Schepens D, Verswijvel G, Kuypers D, et al; Images in Nephrology. Renal cortical nephrocalcinosis. Nephrol Dial Transplant. 2000 Jul;15(7):1080-2.
  7. Ammenti A, Pelizzoni A, Cecconi M, et al; Nephrocalcinosis in children: a retrospective multi-centre study. Acta Paediatr. 2009 Oct;98(10):1628-31. Epub 2009 Jul 1.
  8. Boyce AM, Shawker TH, Hill SC, 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. doi: 10.1210/jc.2012-2747. Epub 2013 Jan 24.
  9. Halbritter J, Baum M, Hynes AM, et al; Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J Am Soc Nephrol. 2015 Mar;26(3):543-51. doi: 10.1681/ASN.2014040388. Epub 2014 Oct 8.
  10. Vervaet BA, Verhulst A, D'Haese PC, et al; Nephrocalcinosis: new insights into mechanisms and consequences. Nephrol Dial Transplant. 2009 Jul;24(7):2030-5. Epub 2009 Mar 18.
  11. Gambaro G, Trinchieri A; Recent advances in managing and understanding nephrolithiasis/nephrocalcinosis. F1000Res. 2016 Apr 18;5:F1000 Faculty Rev-695. doi: 10.12688/f1000research.7126.1. eCollection 2016.

Article history

The information on this page is written and peer reviewed by qualified clinicians.

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