Elevated asymmetric dimethylarginine (ADMA) and inverse correlation between circulating ADMA and glomerular filtration rate in children with sporadic focal segmental glomerulosclerosis (FSGS)

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