NDT Advance Access published online on January 5, 2008
Nephrology Dialysis Transplantation, 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)
1 Department of Paediatric, Kidney, Liver and Metabolic and Nephrologic Diseases, Hannover Medical School, Hannover, Germany 2 Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany 3 Department 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