L-arginine/NO pathway is altered in children with haemolytic-uraemic syndrome (HUS).
The haemolytic uraemic syndrome (HUS) is the most frequent cause of acute renal failure in childhood. We investigated L-arginine/NO pathway in 12 children with typical HUS and 12 age-matched healthy control subjects. Nitrite and nitrate, the major NO metabolites in plasma and urine, asymmetric dimethylarginine (ADMA) in plasma and urine, and dimethylamine (DMA) in urine were determined by GC-MS and GC-MS/MS techniques. Urinary measurements were corrected for creatinine excretion. Plasma nitrate was significantly higher in HUS patients compared to healthy controls (P = 0.021), whereas urine nitrate was borderline lower in HUS patients compared to healthy controls (P = 0.24). ADMA plasma concentrations were insignificantly lower, but urine ADMA levels were significantly lower in the HUS patients (P = 0.019). Urinary DMA was not significantly elevated. In HUS patients, nitrate (R = 0.91) but not nitrite, L-arginine, or ADMA concentrations in plasma correlated with free haemoglobin concentration. Our results suggest that both NO production and ADMA synthesis are decreased in children with typical HUS. We hypothesize that in the circulation of children with HUS a vicious circle between the L-arginine/NO pathway and free haemoglobin-mediated oxidative stress exists. Disruption of this vicious circle by drugs that release NO and/or sulphydryl groups-containing drugs may offer new therapeutic options in HUS.
Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Nele Kirsten
NK
Kanzelmeyer
Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Lars
L
Pape
Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany ; Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Kristine
K
Chobanyan-Jürgens
Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Dimitrios
D
Tsikas
Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Hans
0000-0002-4333-3839
H
Hartmann
Department of Paediatrics, University of Mainz, Langenbeckstraße 1, 55131 Mainz, Germany.
Anne-Jule
AJ
Fuchs
Institute of Biometry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Bernhard
B
Vaske
Department of Paediatric Kidney, Liver and Metabolic Diseases, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Anibh Martin
AM
Das
Department of Medicine III, Klinikum Fulda, Pacelliallee 4, 36043 Fulda, Germany.
Marion
M
Haubitz
Institute of Clinical Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625 Hannover, Germany.
Jens
J
Jordan
Department of Neuropaediatrics, University Children's Hospital, Ruhr University Bochum, Gudrunstraße 56, 44791 Bochum, Germany.
Thomas
T
Lücke
D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism* / Q000652:urine; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D006463:Hemolytic-Uremic Syndrome / Q000097:blood / Q000378:metabolism* / Q000652:urine; D006760:Hospitalization; D006801:Humans; D008297:Male; D009566:Nitrates / Q000097:blood / Q000652:urine; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000097:blood / Q000652:urine; D010530:Peritoneal Dialysis; D015398:Signal Transduction
D006454:Hemoglobins; D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine