Increased protein intake on controlled oxalate diets does not increase urinary oxalate excretion


High animal protein intake is a risk factor for calcium oxalate stone disease. The effect of dietary protein on the urinary excretion of calcium, acid and citrate is well established. However, its effect on oxalate excretion is unclear, due in part to an inadequate control of dietary oxalate intake in previous studies. This relationship warrants clarification due to the proposed important role of the metabolism of amino acids in endogenous oxalate synthesis. In this study, 11 normal subjects consumed controlled oxalate diets containing 0.6, 1.2 and 1.8 g protein/kg body weight/day. The analysis of 24 h urine collections confirmed that as protein intake increased, urinary calcium and glycolate increased and urinary pH and citrate decreased. The increased glycolate excretion was due in part to an increased hydroxyproline, but not glycolate consumption. Total daily urinary oxalate excretion did not change. When indexed to creatinine there was a small but significant decrease in oxalate excretion. This is most likely due to hyperfiltration. These results indicate that as dietary protein intake increases, the catabolism of diet-derived amino acids is not associated with an increased endogenous oxalate synthesis in normal subjects.

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  1. 1.

    Goodman HO, Holmes RP, Assimos DG (1995) Genetic factors in calcium oxalate stone disease. J Urol 153:301–307. doi:10.1097/00005392-199502000-00003

    PubMed  Article  CAS  Google Scholar 

  2. 2.

    Taylor EN, Stampfer MJ, Curhan GC (2004) Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 15:3225–3232. doi:10.1097/01.ASN.0000146012.44570.20

    PubMed  Article  Google Scholar 

  3. 3.

    Taylor EN, Curhan GC (2007) Oxalate intake and the risk for nephrolithiasis. J Am Soc Nephrol 18:2198–2204. doi:10.1681/ASN.2007020219

    PubMed  Article  CAS  Google Scholar 

  4. 4.

    Taylor EN, Curhan GC (2008) Fructose consumption and the risk of kidney stones. Kidney Int 73:207–212. doi:10.1038/

    PubMed  Article  CAS  Google Scholar 

  5. 5.

    Breslau NA, Brinkley L, Hill KD et al (1988) Relationship of animal protein-rich diet to kidney stone formation and calcium metabolism. J Clin Endocrinol Metab 66:140–146

    PubMed  CAS  Article  Google Scholar 

  6. 6.

    Nguyen Q-V, Kalin A, Drouve U et al (2001) Sensitivity to meat protein intake and hyperoxaluria in idiopathic calcium oxalate stone formers. Kidney Int 59:2273–2281

    PubMed  CAS  Google Scholar 

  7. 7.

    Holmes RP, Goodman HO, Hart LJ et al (1993) Relationship of protein intake to urinary oxalate and glycolate excretion. Kidney Int 44:366–372. doi:10.1038/ki.1993.253

    PubMed  Article  CAS  Google Scholar 

  8. 8.

    Robertson WG, Heyburn PJ, Peacock M et al (1979) The effect of high animal protein intake on the risk of calcium stone-formation in the urinary tract. Clin Sci (Lond) 57:285–288

    CAS  Google Scholar 

  9. 9.

    Robertson WG, Peacock M, Heyburn PJ et al (1979) Should recurrent calcium oxalate stone formers become vegetarians? Br J Urol 51:427–431. doi:10.1111/j.1464-410X.1979.tb03570.x

    PubMed  Article  CAS  Google Scholar 

  10. 10.

    Giannini S, Nobile M, Sartori L et al (1999) Acute effects of moderate dietary protein restriction in patients with idiopathic hypercalciuria and calcium nephrolithiasis. Am J Clin Nutr 69:267–271

    PubMed  CAS  Google Scholar 

  11. 11.

    Butz M, Hoffmann H, Kohlbecker G (1980) Dietary influence on serum and urinary oxalate in healthy subjects and oxalate stone formers. Urol Int 35:309–315

    PubMed  CAS  Article  Google Scholar 

  12. 12.

    Conyers RA, Need AG, Bracken A et al (1985) The effect of short-term dietary changes on biochemical values in blood and urine and on some urinary risk factors for calcium oxalate stone formation in humans. Int J Vitam Nutr Res Suppl 28:135–152

    PubMed  CAS  Google Scholar 

  13. 13.

    Fellstrom B, Danielson BG, Karlstrom B et al (1984) Effects of high intake of dietary animal protein on mineral metabolism and urinary supersaturation of calcium oxalate in renal stone formers. Br J Urol 56:263–269. doi:10.1111/j.1464-410X.1984.tb05384.x

    PubMed  Article  CAS  Google Scholar 

  14. 14.

    Marangella M, Bianco O, Martini C et al (1989) Effect of animal and vegetable protein intake on oxalate excretion in idiopathic calcium stone disease. Br J Urol 63:348–351. doi:10.1111/j.1464-410X.1989.tb05214.x

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Holmes RP, Assimos DG (1998) Glyoxylate synthesis, and its modulation and its influence on oxalate synthesis. J Urol 160:1617–1624. doi:10.1016/S0022-5347(01)62363-2

    PubMed  Article  CAS  Google Scholar 

  16. 16.

    Cook DA, Henderson LM (1969) The formation of oxalic acid from the side chain of aromatic amino acids in the rat. Biochim Biophys Acta 184:404–411

    PubMed  CAS  Google Scholar 

  17. 17.

    Gambardella RL, Richardson KE (1977) The pathways of oxalate formation from phenylalanine, tyrosine, tryptophan and ascorbic acid. Biochim Biophys Acta 499:156–168

    PubMed  CAS  Google Scholar 

  18. 18.

    Knight J, Jiang J, Assimos DG et al (2006) Hydroxyproline ingestion and urinary oxalate and glycolate excretion. Kidney Int 70:1929–1934. doi:10.1038/

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Schwarz K (1961) Separation of enol and keto tautomers of aromatic pyruvic acids by paper chromatography. Arch Biochem Biophys 92:168–175. doi:10.1016/0003-9861(61)90232-6

    PubMed  Article  CAS  Google Scholar 

  20. 20.

    Juillet B, Fouillet H, Bos C et al (2008) Increasing habitual protein intake results in reduced postprandial efficiency of peripheral, anabolic wheat protein nitrogen use in humans. Am J Clin Nutr 87:666–678

    PubMed  CAS  Google Scholar 

  21. 21.

    Holmes RP, Kennedy M (2000) Estimation of the oxalate content of foods and daily oxalate intake. Kidney Int 57:1662–1667. doi:10.1046/j.1523-1755.2000.00010.x

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Tiselius HG (1991) Aspects on estimation of the risk of calcium oxalate crystallization in urine. Urol Int 47:255–259

    PubMed  CAS  Google Scholar 

  23. 23.

    Wagner EA, Falciglia GA, Amlal H et al (2007) Short-term exposure to a high-protein diet differentially affects glomerular filtration rate but not acid–base balance in older compared to younger adults. J Am Diet Assoc 107:1404–1408. doi:10.1016/j.jada.2007.05.003

    PubMed  Article  CAS  Google Scholar 

  24. 24.

    Siener R, Ebert D, Nicolav C et al (2003) Dietary risk factors for hyperoxaluria in calcium oxalate stone formers. Kidney Int 63:1037–1043. doi:10.1046/j.1523-1755.2003.00807.x

    PubMed  Article  Google Scholar 

  25. 25.

    Nguyen NU, Dumoulin G, Henriet M-T et al (1995) Increase in urinary calcium and oxalate after fructose infusion. Horm Metab Res 27:155–158. doi:10.1055/s-2007-979929

    PubMed  Article  CAS  Google Scholar 

  26. 26.

    Rofe AM, James HM, Bais R et al (1980) The production of [14C] oxalate during the metabolism of [14C] carbohydrates in isolated rat hepatocytes. Aust J Exp Biol Med Sci 58:103–116. doi:10.1038/icb.1980.10

    PubMed  Article  CAS  Google Scholar 

  27. 27.

    Holmes RP, Goodman HO, Assimos DG (2001) Contribution of dietary oxalate to urinary oxalate excretion. Kidney Int 59:270–276. doi:10.1046/j.1523-1755.2001.00488.x

    PubMed  Article  CAS  Google Scholar 

  28. 28.

    Reddy ST, Wang CY, Sakhaee K et al (2002) Effect of low-carbohydrate high-protein diets on acid-base balance, stone-forming propensity, and calcium metabolism. Am J Kidney Dis 40:265–274. doi:10.1053/ajkd.2002.34504

    PubMed  Article  CAS  Google Scholar 

  29. 29.

    Gill HS, Rose GA (1986) Mild metabolic hyperoxaluria and its response to pyridoxine. Urol Int 41:393–396

    PubMed  CAS  Article  Google Scholar 

  30. 30.

    Harris KS, Richardson KE (1980) Glycolate in the diet and its conversion to urinary oxalate in the rat. Invest Urol 18:106–109

    PubMed  CAS  Google Scholar 

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This research was supported by NIH grants RO1 DK73732 and MO1 RR07122. We gratefully acknowledge the skilled assistance of Martha Kennedy, Diane Dezern and the staff of the GCRC with these experiments.

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Correspondence to John Knight.

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Knight, J., Easter, L.H., Neiberg, R. et al. Increased protein intake on controlled oxalate diets does not increase urinary oxalate excretion. Urol Res 37, 63–68 (2009).

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  • Dietary protein
  • Oxalate excretion
  • Oxalate synthesis
  • Glycolate
  • Hydroxyproline