Theoretical and laboratory investigations of the effects of hydroxyproline ingestion on the metabolic and physicochemical risk factors for calcium oxalate kidney stone formation in a small group of healthy subjects

Int Urol Nephrol. 2019 Jul;51(7):1121-1127. doi: 10.1007/s11255-019-02186-2. Epub 2019 Jun 3.

Abstract

Purpose: Dietary hydroxyproline may be involved in the endogenous synthesis of oxalate. Glycolate, produced during the metabolism of hydroxyproline, may exert physicochemical effects on urinary calcium by virtue of its dihydroxycarboxylic acid structure. The aim of this study was to investigate these possible stone-risk scenarios.

Methods: We modelled the effect of different glycolic acid concentrations on ionized calcium (iCa2+) and relative supersaturation (RSS) of calcium oxalate (CaOx) using the program JESS. Thereafter, three healthy white males and two healthy black males ingested 30 g gelatin for 3 days. 24-h urines were collected at baseline and after completion of the protocol. Urines were analysed for physicochemical risk factors and for iCa2+ and glycolic acid. Speciation concentrations and RSS values were calculated.

Results: Theoretical modelling showed that binding between calcium and glycolate does not occur and that iCa2+ and RSS CaOx are unaffected. However, after ingestion of hydroxyproline, iCa2+ decreased significantly. Urinary pH and glycolate increased significantly. Oxalate excretion and RSS CaOx did not change CONCLUSIONS: We attribute the decrease in iCa2+ to increases in the concentrations of several Ca-phosphate species, the formation of which is due to the increase in pH. We speculate that the absence of an increase in oxalate excretion despite an increase in glycolate excretion may be due to the mixed racial composition of our test group in which some pathways may be preferred to others. Our findings alert stone researchers to the importance of measuring urinary pH in their workup of subjects and to select racially homogenous groups for investigation.

Keywords: Endogenous production of glycolate; Endogenous production of oxalate; Hydroxyproline ingestion; Modelling glycolate–calcium binding; Racial dependence of hydroxyproline metabolism.

MeSH terms

  • Adult
  • Biochemical Phenomena
  • Calcium Oxalate* / metabolism
  • Calcium Oxalate* / urine
  • Dietary Exposure
  • Glycolates* / metabolism
  • Glycolates* / urine
  • Healthy Volunteers
  • Humans
  • Hydrogen-Ion Concentration
  • Hydroxyproline / metabolism*
  • Male
  • Nephrolithiasis* / diagnosis
  • Nephrolithiasis* / metabolism
  • Risk Assessment / methods
  • Risk Factors
  • Urinalysis / methods

Substances

  • Glycolates
  • glycolic acid
  • Calcium Oxalate
  • Hydroxyproline

Supplementary concepts

  • Nephrolithiasis, Calcium Oxalate