NDT Advance Access originally published online on January 5, 2008
Nephrology Dialysis Transplantation 2008 23(2):734-740; doi:10.1093/ndt/gfm761
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Elevated asymmetric dimethylarginine (ADMA) and inverse correlation between circulating ADMA and glomerular filtration rate in children with sporadic focal segmental glomerulosclerosis (FSGS)
1Department of Paediatric, Kidney, Liver and Metabolic and Nephrologic Diseases, Hannover Medical School, Hannover, Germany, 2Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany and 3Department of Paediatrics, University of Zurich, Zurich, Switzerland
Correspondence and offprint requests to: Thomas Lücke, Department of Paediatrics, Hannover Medical School, Carl Neuberg Str.1, D-30625, Hannover, Germany. Tel: +49-0511-532-3220; Fax: +49-0511-532-8073; E-mail: luecke.thomas{at}mh-hannover.de
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Abstract |
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Background. Steroid-resistant nephrotic syndromes (NS) with focal and segmental glomerulosclerosis (FSGS) can be differentiated into sporadic and syndromic forms. In sporadic NS, a circulating FSGS-factor is discussed in the pathogenesis and is thought to inhibit the synthesis of nitric oxide (NO) from L-arginine by blocking the NO synthase (NOS). Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of all types of NOS. In a previous study we did not find an elevation of ADMA in a syndromic form of FSGS, the Schimke-immuno-osseous dysplasia. Here we report for the first time data on the L-arginine/NO pathway in sporadic FSGS of childhood.
Methods. Nine children (5 to 18 years of age) suffering from sporadic FSGS and age-matched healthy controls were investigated. ADMA in plasma and urine as well as L-arginine in plasma were determined by gas chromatography–tandem mass spectrometry. The NO metabolites nitrate and nitrite were measured in plasma and urine by gas chromatography–mass spectrometry (GC-MS). The ADMA metabolite dimethylamine (DMA) was measured in urine by GC-MS.
Results. We found elevated plasma levels of ADMA in children suffering from sporadic FSGS compared to healthy controls (851 nmol/L versus 684 nmol/L, P = 0.008). An inverse correlation between ADMA and glomerular filtration rate (GFR) was found in sporadic FSGS (Pearson's correlation coefficient –0.784, P = 0.012).
Conclusion. Our study suggests that ADMA synthesis is elevated in sporadic FSGS. This finding argues for the involvement of ADMA in the pathogenesis of this disease in childhood.
Keywords: ADMA; DMA; FSGS; NO pathway; sporadic
Received for publication: 19.10.06
Accepted in revised form: 24. 9.07