Skip to main content
SpringerLink
Log in

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

  • Urology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Knight J, Jiang J, Assimos DG, Holmes RP (2006) Hydroxyproline ingestion and urinary oxalate and glycolate excretion. Kidney Int 70:1929–1934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Akiduki S, Ito H, Morishita K, Kamimura A (2015) A single-blind, parallel trial of L-hydroxyproline in healthy adult subjects. Urolithiasis 43:289–292

    Article  PubMed  PubMed Central  Google Scholar 

  3. Frederick EW, Rabkin MT, RitchieRH Smith LH (1963) Studies on primary hyperoxaluria—in vivo demonstration of a defect in glyoxylate metabolism. N Engl J Med 269:821–829

    Article  CAS  PubMed  Google Scholar 

  4. Robijn S, Hoppe B, Vervaet BA, D’Haese PC, Verhulst A (2011) Hyperoxaluria: a gut-kidney axis? Kidney Int 80:1146–1158

    Article  CAS  PubMed  Google Scholar 

  5. Rodgers A, Jackson G, Ravenscroft N, Cele P (2014) Effect of hydroxyproline ingestion on urinary glycolate and oxalate excretion, and calcium oxalate supersaturation. J Urol 191(supplement):270–271

    Google Scholar 

  6. Siener R, Hesse A (2002) The effect of different diets on urine composition and the risk of calcium oxalate crystallisation in healthy subjects. Eur Urol 42:289–296

    Article  PubMed  Google Scholar 

  7. May PM, Murray K (1991) JESS, a joint expert speciation system-1. Talanta 38:1409–1417

    Article  CAS  PubMed  Google Scholar 

  8. Niederwieser A, Matasovic A, Leumann E (1978) Glycolic acid in urine. A colorimetric method with values in normal adult controls and in patients with primary hyperoxaluria. Clin Chim Acta 89:13–23

    Article  CAS  PubMed  Google Scholar 

  9. Allie-Hamdulay S, Rodgers A (2005) Prophylactic and therapeutic properties of a sodium citrate preparation in the management of calcium oxalate urolithiasis: randomized, placebo-controlled trial. Urol Res 33:116–124

    Article  CAS  PubMed  Google Scholar 

  10. Ryall RL, Hibberd CM, Marshall VR (1985) A method for studying inhibitory activity in whole urine. Urol Res 13:285–289

    Article  CAS  PubMed  Google Scholar 

  11. Kim JS, Laskowich ER, Arumugham RG, Kaiser RE, MacMichael GJ (2005) Determination of saccharide content in pneumococcal polysaccharides and conjugate vaccines. Anal Biochem 347:244–262

    Article  CAS  Google Scholar 

  12. Rodgers A, Allie-Hamdulay S, Jackson G (2005) Therapeutic action of citrate in urolithiasis explained by chemical speciation: increase in pH is the determinant factor. Nephrol Dial Transplant 21:361–369

    Article  CAS  PubMed  Google Scholar 

  13. Buchinsky DA, Asplin JR, Grynpas MD, Evan AP, Parker WR, Alexander KM, Coe FL (2002) Calcium oxalate stone formation in genetic hypercalciuric stone-forming rats. Kidney Int 61:975–987

    Article  Google Scholar 

  14. Takayama T, Fujita K, Suzuki K, Sakaguchi M, Fugie M, Nagai E, Watanabe S, Ichiyama A, Ogawa Y (2003) Control of oxalate formation from L-hydroxyproline in liver mitochondria. J Am Soc Nephrol 14(4):939–946

    Article  CAS  PubMed  Google Scholar 

  15. Khan SR, Glenton PA, Byer KJ (2006) Modeling of hyperoxaluric calcium oxalate nephrolithiasis: experimental induction of hyperoxaluria by hydroxyl-L-proline. Kidney Int 70:914–923

    Article  CAS  PubMed  Google Scholar 

  16. Kaplon DM, Penniston KL, Darriet C, Crenshaw TD, Nakada SY (2010) Hydroxyproline-induced hyperoxaluria using acidified and traditional diets in the porcine model. J Endourol 24(3):355–359

    Article  PubMed  Google Scholar 

  17. Dill DB, Horvath SM (1941) The influence of gelatin ingestion upon the creatinine-creatine excretion of normal men. Am J Physiol 133(3):520–524

    Article  CAS  Google Scholar 

  18. Prockop DJ, Sjoerdsma A (1961) Significance of urinary hydroxyproline in man. J Clin Inv 40(5):843–849

    Article  CAS  Google Scholar 

  19. Swaminathan R (2003) Magnesium metabolism and its disorders. Cin Biochem Rev 24:47–66

    CAS  Google Scholar 

  20. Curhan GC, Willett WC, Speizer FE, Stamfer MJ (2001) Twenty-four-hour urine chemistries and the risk of kidney stones among women and men. Kidney Int 59:2290–2298

    Article  CAS  PubMed  Google Scholar 

  21. Holmes RP, Goodman HO, Hart LJ, Assimos DJ (1993) Relationship of protein intake to urinary oxalate and glycolate excretion. Kidney Int 44:366–372

    Article  CAS  PubMed  Google Scholar 

  22. Perinpam M, Ware EB, Smith JA, Turner ST, Kardia S, Lieske JC (2015) Effect of demographics on excretion of key urinary factors related to kidney stone risk. Urology 86:690–696

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lewandowski S, Rodgers A, Schloss I (2001) The influence of a high-oxalate/low-calcium diet on calcium oxalate renal stone risk factors in non-stone-forming black and white South African subjects. Br J Urol Int 87:307–311

    Article  CAS  Google Scholar 

  24. Rodgers A, Lewandowski S (2002) Effects of five different lithogenic diets on urinary risk factors for calcium oxalate stone formation: evidence of different renal handling mechanisms in different race groups. J Urol 168:931–936

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors wish to thank the South African National Research Foundation, the South African Medical Research Council and the University of Cape Town for financial support.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Cape Town, Rondebosch, 7701, Cape Town, South Africa

    Allen Rodgers, Phindile Cele, Neil Ravenscroft, Cesarina Edmonds-Smith & Graham Jackson

Authors
  1. Allen Rodgers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Phindile Cele
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Neil Ravenscroft
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cesarina Edmonds-Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Graham Jackson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Allen Rodgers.

Ethics declarations

Conflict of interest

The authors declare that there are no conflicts of interest.

Ethical approval

All procedures were performed in accordance with the ethical standards of the University of Cape Town and with the 1964 Helsinki Declaration and its later amendments. The study was approved by the Faculty of Human and Health Sciences Research Ethics Committee of the University of Cape Town.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rodgers, A., Cele, P., Ravenscroft, N. et al. 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 51, 1121–1127 (2019). https://doi.org/10.1007/s11255-019-02186-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-019-02186-2

Keywords

Search

Navigation