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Idiopathic hypercalciuria and formation of calcium renal stones

Nature Reviews Nephrology volume 12, pages 519–533 (2016)Cite this article

Subjects

Key Points

  • Idiopathic calcium stones are always accompanied by mineral deposits: interstitial deposits of apatite in patients with calcium oxalate (CaOx) stones or calcium phosphate (CaP) plugs in those with CaP stones

  • Overgrowth of CaOx stones on plaque depends on the formation of an initial CaP phase; urine saturations of CaP and CaOx might, therefore, be equally important

  • Microliths form on the open ends of tubule plugs but proof that these microliths can grow into clinically relevant stones is lacking

  • Patients with tubule plugs who form CaP stones show varying degrees of cortical fibrosis and nephron loss

  • Trial data support the use of high fluid intake, potassium citrate, thiazide diuretic agents and a reduced sodium diet for prevention of recurrent calcium renal stones

  • As idiopathic hypercalciuria arises from reduced renal tubule calcium reabsorption and is associated with negative calcium balance and bone disease, management with a low calcium diet is contraindicated

Abstract

The most common presentation of nephrolithiasis is idiopathic calcium stones in patients without systemic disease. Most stones are primarily composed of calcium oxalate and form on a base of interstitial apatite deposits, known as Randall's plaque. By contrast some stones are composed largely of calcium phosphate, as either hydroxyapatite or brushite (calcium monohydrogen phosphate), and are usually accompanied by deposits of calcium phosphate in the Bellini ducts. These deposits result in local tissue damage and might serve as a site of mineral overgrowth. Stone formation is driven by supersaturation of urine with calcium oxalate and brushite. The level of supersaturation is related to fluid intake as well as to the levels of urinary citrate and calcium. Risk of stone formation is increased when urine citrate excretion is <400 mg per day, and treatment with potassium citrate has been used to prevent stones. Urine calcium levels >200 mg per day also increase stone risk and often result in negative calcium balance. Reduced renal calcium reabsorption has a role in idiopathic hypercalciuria. Low sodium diets and thiazide-type diuretics lower urine calcium levels and potentially reduce the risk of stone recurrence and bone disease.

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Figure 1: Interstitial plaque and corresponding attachment site on a calcium oxalate (CaOx) stone.
Figure 2: Sites of interstitial plaque in idiopathic calcium oxalate (CaOx) stone formers.
Figure 3: Bellini duct plugs with overgrowths in patients who formed calcium stones.
Figure 4: Renal papilla of a patient who formed brushite stones.
Figure 5: Renal papilla of patients who formed idiopathic apatite stones.
Figure 6: Renal cortical changes in patients who formed calcium stones.
Figure 7: Effect of urine flow rate on calcium oxalate and calcium phosphate supersaturations.

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Acknowledgements

The authors' work is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (PO1 DK56788).

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Authors and Affiliations

  1. Nephrology Section MC 5100, University of Chicago Medicine, 5841 S. Maryland Avenue, Chicago, 60637, Illinois, USA

    Fredric L. Coe & Elaine M. Worcester

  2. Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, MS 5055, Indianapolis, IN 46220, Indiana, USA

    Andrew P. Evan

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Coe, F., Worcester, E. & Evan, A. Idiopathic hypercalciuria and formation of calcium renal stones. Nat Rev Nephrol 12, 519–533 (2016). https://doi.org/10.1038/nrneph.2016.101

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