Nephrol Dial Transplant (2002) 17: 1032-1036
© 2002 European Renal Association-European Dialysis and Transplant Association
Plasma pteridine concentrations in patients with chronic renal failure
1 The Division of Nephrology and Hypertension, Jikei University School of Medicine, Tokyo and 2 Department of Dental Pharmacology, Meikai University School of Dentistry, Sakado, Saitama, Japan
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.
Keywords: chronic renal failure; dihydrobiopterin; NADH; nitric oxide; superoxide; tetrabiopterin
Correspondence and offprint requests to: Keitaro Yokoyama MD, The Division of Nephrology and Hypertension, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo 105-8471, Japan. Email: keitaro{at}mrj.biglobe.ne.jp
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