Urinary ortho-tyrosine excretion in diabetes mellitus and renal failure: evidence for hydroxyl radical production

Kidney Int. 2005 Nov;68(5):2281-7. doi: 10.1111/j.1523-1755.2005.00687.x.


Background: Phenylalanine is converted to para- and ortho-tyrosine by hydroxyl free radical, or to para-tyrosine by the phenylalanine hydroxylase enzyme. The aim of this study was to measure para- and ortho-tyrosine in the urine and plasma of patients with chronic renal disease and/or diabetes, to obtain information on the renal handling of the different tyrosine isomers and, furthermore, to measure urinary levels of 8-epi-prostaglandin-F(2alpha), a marker of lipid peroxidation.

Methods: In our cross-sectional study we measured para-, ortho-tyrosine, and phenylalanine levels, using high performance liquid chromatography and 8-epi-prostaglandin-F(2alpha) with enzyme-linked immunosorbent assay (ELISA). We compared 4 groups: (1) controls (CONTR, N = 14), (2) patients with chronic kidney disease (CKD, N = 12), (3) patients with type 2 diabetes mellitus (DIAB, N = 17), (4) patients with chronic kidney disease and type 2 diabetes (DIAB-CKD, N = 19).

Results: We found a decreased plasma para-tyrosine level and decreased urinary para-tyrosine excretion in CKD patients, while the fractional excretion of para-tyrosine was similar in all 4 groups, approximately 1%. There was no difference in the plasma ortho-tyrosine levels between the groups. However, urinary ortho-tyrosine excretion was higher in all 3 groups of patients than in the CONTR group, and higher in DIAB and in DIAB-CKD patients than in CKD patients. The fractional excretion of ortho-tyrosine was significantly higher in DIAB and in DIAB-CKD patients than in the CONTR group. The fractional excretion of ortho-tyrosine exceeded 100% in the 2 diabetic groups. Urinary 8-epi-prostaglandin-F(2alpha)/creatinine ratio did not correlate with urinary ortho-tyrosine excretion.

Conclusion: The difference between para-tyrosine levels of the groups is probably due to renal impairment, while there is indirect evidence for an increased tubular secretion or production of ortho-tyrosine in the kidney in diabetic patients with or without CKD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cross-Sectional Studies
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / urine*
  • Female
  • Humans
  • Hydroxyl Radical / metabolism*
  • Kidney / metabolism
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / urine*
  • Male
  • Middle Aged
  • Phenylalanine / chemistry
  • Phenylalanine / metabolism
  • Tyrosine / blood
  • Tyrosine / chemistry
  • Tyrosine / urine*


  • Hydroxyl Radical
  • Tyrosine
  • Phenylalanine
  • 2-tyrosine