Evidence for disordered acid-base handling in calcium stone-forming patients

Am J Physiol Renal Physiol. 2020 Feb 1;318(2):F363-F374. doi: 10.1152/ajprenal.00400.2019. Epub 2019 Dec 2.


In stone formers (SFs) with idiopathic hypercalciuria, urine pH governs the mineral phase of stones. Calcium phosphate (CaP) SFs have higher urine pH than calcium oxalate (CaOx) SFs. Normal women have higher urine pH than men on fixed diets, accompanied by greater absorption of food alkali. Female CaP and male CaOx SFs have similar urine pH as same sex normal individuals, but male CaP and female CaOx SFs may have abnormal acid-base handling. We studied 25 normal individuals (13 men and 12 women), 17 CaOx SFs (11 men and 6 women), and 15 CaP SFs (8 men and 7 women) on fixed diets. Urine and blood samples were collected under fasting and fed conditions. Female CaOx SFs had lower urine pH and lower alkali absorption, fed, compared with normal women; their urine NH4 was higher and urine citrate excretion lower than in normal women, consistent with their higher net acid excretion. Male CaOx SFs had higher urine citrate excretion and higher serum ultrafilterable citrate levels than normal men. Both male and female CaP SFs had higher urine pH fasting than same sex normal individuals, but only men were higher in the fed period, and there were no differences from normal in gut alkali absorption. CaP SFs of both sexes had higher urine NH4 and lower urine citrate than same sex normal individuals. The lower urine pH of female CaOx SFs seems related to decreased gut alkali absorption, while the higher pH of CaP SFs, accompanied by higher urine NH4 and lower urine citrate, suggests a proximal tubule disorder.

Keywords: acid-base; calcium oxalate; calcium phosphate; kidney stones.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acid-Base Equilibrium*
  • Acid-Base Imbalance / blood
  • Acid-Base Imbalance / diagnosis
  • Acid-Base Imbalance / physiopathology
  • Acid-Base Imbalance / urine*
  • Adult
  • Ammonium Compounds / urine
  • Biomarkers / blood
  • Biomarkers / urine
  • Calcium Oxalate / urine*
  • Calcium Phosphates / urine*
  • Case-Control Studies
  • Citric Acid / urine
  • Crystallization
  • Diet / adverse effects
  • Female
  • Gastrointestinal Absorption
  • Humans
  • Hydrogen-Ion Concentration
  • Hypercalciuria / blood
  • Hypercalciuria / diagnosis
  • Hypercalciuria / physiopathology
  • Hypercalciuria / urine*
  • Kidney Calculi / blood
  • Kidney Calculi / diagnosis
  • Kidney Calculi / physiopathology
  • Kidney Calculi / urine*
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / physiopathology
  • Male
  • Middle Aged
  • Risk Factors
  • Sex Factors
  • Young Adult


  • Ammonium Compounds
  • Biomarkers
  • Calcium Phosphates
  • Calcium Oxalate
  • Citric Acid
  • calcium phosphate