Pathophysiology-based treatment of idiopathic calcium kidney stones

Clin J Am Soc Nephrol. 2011 Aug;6(8):2083-92. doi: 10.2215/CJN.11321210.


Idiopathic calcium oxalate (CaOx) stone-formers (ICSFs) differ from patients who make idiopathic calcium phosphate (CaP) stones (IPSFs). ICSFs, but not IPSFs, form their stones as overgrowths on interstitial apatite plaque; the amount of plaque covering papillary surface is positively correlated with urine calcium excretion and inversely with urine volume. The amount of plaque predicts the number of recurrent stones. The initial crystal overgrowth on plaque is CaP, although the stone is mainly composed of CaOx, meaning that lowering supersaturation (SS) for CaOx and CaP is important for CaOx stone prevention. IPSFs, unlike ICSFs, have apatite crystal deposits in inner medullary collecting ducts, which are associated with interstitial scarring. ICSFs and IPSFs have idiopathic hypercalciuria, which is due to decreased tubule calcium reabsorption, but sites of abnormal reabsorption may differ. Decreased reabsorption in proximal tubules (PTs) delivers more calcium to the thick ascending limb (TAL), where increased calcium reabsorption can load the interstitium, leading to plaque formation. The site of abnormal reabsorption in IPSFs may be the TAL, where an associated defect in bicarbonate reabsorption could produce the higher urine pH characteristic of IPSFs. Preventive treatment with fluid intake, protein and sodium restriction, and thiazide will be effective in ICSFs and IPSFs by decreasing urine calcium concentration and CaOx and CaP SS and may also decrease plaque formation by increased PT calcium reabsorption. Citrate may be detrimental for IPSFs if urine pH rises greatly, increasing CaP SS. Future trials should examine the question of appropriate treatment for IPSFs.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Calcium Oxalate / metabolism*
  • Calcium Oxalate / urine
  • Calcium Phosphates / metabolism*
  • Calcium Phosphates / urine
  • Citrates / therapeutic use
  • Crystallization
  • Diet, Protein-Restricted
  • Diet, Sodium-Restricted
  • Fluid Therapy
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism*
  • Kidney / physiopathology
  • Kidney Calculi / metabolism
  • Kidney Calculi / physiopathology
  • Kidney Calculi / prevention & control*
  • Secondary Prevention
  • Sodium Chloride Symporter Inhibitors / therapeutic use
  • Treatment Outcome


  • Calcium Phosphates
  • Citrates
  • Sodium Chloride Symporter Inhibitors
  • Calcium Oxalate