Plasma pteridine concentrations in patients with chronic renal failure

Keitaro Yokoyama, Masamich Tajima, Hiraku Yoshida, Masaaki Nakayama, Goro Tokutome, Hiroshi Sakagami, Tatsuo Hosoya

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Abstract

Background. Pteridine metabolism is impaired in the uraemic state. This may affect cardiovascular function and contribute to malnutrition. We wished to clarify further the impact of impaired pteridine metabolism. Methods. Using the HPLC method, the plasma concentrations of endogenous pteridines were determined in 64 patients with chronic renal failure (33 on intermittent haemodialysis (HD) treatment vs 31 not yet on renal replacement therapy), and in 18 healthy controls. The patients were classified into three groups on the basis of creatinine clearance (Ccr): group (a), Ccr > 60 ml/min; group (b), Ccr=10-60 ml/min; group (c), all patients receiving HD. Results. Total neopterin (NP) and biopterin (BP) levels and the NP/BP ratio (a biomarker for macrophage activity) were significantly higher, whereas tetrahydrobiopterin (BH4)/dihydrobiopterin (BH2) ratio (a biomarker for nitric oxide synthase and phenylalanine hydroxylase activities) was significantly lower in group (c) (118.9 ± 11.7 ng/ml, 18.8 ± 1.2 ng/ml, 6.79 ± 0.53, and 0.26 ± 0.06) than in healthy subjects (5.17 ± 0.29 ng/ml, 2.83 ± 0.19 ng/ml, 1.92 ± 0.13, and 1.15 ± 0.11; P<0.01). These significant differences were also observed between control and group (b) (12.4 ± 2.20 ng/ml, 4.48 ± 0.36 ng/ml, 2.81 ± 0.48, and 0.74 ± 0.08; P<0.01). In groups (a) and (b), significant negative correlations were found between Ccr and the total NP level (r = -0.663, P < 0.01), the total BP level (r = -0.492, P < 0.01), the BH2 level (r = -0.677, P < 0.01), and the NP/BP ratio (r = -0.493, P < 0.01). Conversely, significant positive correlations were found between Ccr and the BH4/BH2 ratio (r = 0.602, P < 0.01). Conclusion. The reduction of quinoid-type BH2 to BH4 is modified in patients with advanced chronic renal failure, before and after the initiation of regular HD treatment. These metabolic alterations may play a role in the impaired macrophage, endothelial constitutive nitric oxide synthase, or phenylalanine hydroxylase (PH) activities observed in such patients.

Original languageEnglish
Pages (from-to)1032-1036
Number of pages5
JournalNephrology Dialysis Transplantation
Volume17
Issue number6
Publication statusPublished - 2002 Jul 20

Keywords

  • Chronic renal failure
  • Dihydrobiopterin
  • NADH
  • Nitric oxide
  • Superoxide
  • Tetrabiopterin

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

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  • Cite this

    Yokoyama, K., Tajima, M., Yoshida, H., Nakayama, M., Tokutome, G., Sakagami, H., & Hosoya, T. (2002). Plasma pteridine concentrations in patients with chronic renal failure. Nephrology Dialysis Transplantation, 17(6), 1032-1036.