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

TY - JOUR

T1 - Elevated asymmetric dimethylarginine (ADMA) and inverse correlation between circulating ADMA and glomerular filtration rate in children with sporadic focal segmental glomerulosclerosis (FSGS).

AU - Lücke, Thomas

AU - Kanzelmeyer, Nele

AU - Chobanyan, Kristine

AU - Tsikas, Dimitrios

AU - Franke, Doris

AU - Kemper, Markus J.

AU - Ehrich, Jochen H H

AU - Das, Anibh M

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

M3 - SCORING: Zeitschriftenaufsatz

VL - 23

SP - 734

EP - 740

JO - NEPHROL DIAL TRANSPL

JF - NEPHROL DIAL TRANSPL

SN - 0931-0509

IS - 2

M1 - 2

ER -