Pterin Metabolism In Haemodialysis Patients

Abstract

Summary Patients undertaking maintenance haemodialysis may develop a variety of neurological disorders, the most serious of which is aluminium induced encephalopathy. Abnormally raised serum concentrations of pterins are found in dialysis patients, and neonates with tetrahydrobiopterin deficiency develop mental dysfunction. Dihydropteridine reductase, essential for maintenance of normal levels of tetrahydrobiopterin, is inhibited when aluminium is added to brain homogenate at similar concentrations to those found in aluminium encephalopathy. We have previously shown that erythrocyte dihydropteridine reductase activity was reduced in non-encephalopathic dialysis patients and inversely related to serum aluminium concentration. Concentrations of serum biopterin derivatives were raised but not related to either aluminium or dihydropteridine reductase. In this study of 17 haemodialysis patients, serum biopterin (13.6 ± 1.3 μg/l) and neopterin (66.2 ± 7.4 μg/l) concentrations were raised compared with normal subjects' biopterin (2.4 ± 0.4 g/l) and neopterin (2.8 ± 0.4 μg/l) values (p = 0.0001). When neopterin and biopterin concentrations were corrected for predialysis serum creatinine a weak relationship appeared between them (r = 0.49, P = 0.04). Erythrocyte dihydropteridine reductase was not related to the creatinine corrected neopterin (r = -0.5, p = 0.2), but there was a significant relationship between DHPR and corrected biopterin (r = 0.986, p = 0.0001) and between corrected biopterin and bone aluminium content (r = 0.68, P = 0.03). Our results support the possibility that aluminium causes changes in pterin metabolism which are analogous to those found in Type II hyperphenylalaninaemia. Serum biopterin concentration, corrected for pre-dialysis serum creatinine, can be used satisfactorily to study tetrahydrobiopterin metabolism in haemodialysis patients. However neopterin/biopterin ratios are unpredictably disturbed and cannot be so used. Serum neopterin concentrations are raised more than anticipated from the biopterin concentrations, and this may be due to neopterin release from macrophages activated by dialysis membranes and/or reduced conversion of dihydroneopterin triphosphate to tetrahydrobiopterin.