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).


CONCLUSIONS
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.
Lücke
Thomas
T
Department of Paediatric, Kidney, Liver and Metabolic and Nephrologic Diseases, Hannover Medical School, Carl Neuberg Str.1, D-30625, Hannover, Germany. luecke.thomas@mh-hannover.de
Kanzelmeyer
Nele
N
Chobanyan
Kristine
K
Tsikas
Dimitrios
D
Franke
Doris
D
Kemper
Markus J
MJ
Ehrich
Jochen H H
JH
Das
Anibh M
AM
D000293:Adolescent; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005919:Glomerular Filtration Rate; D005923:Glomerulosclerosis, Focal Segmental / Q000097:blood* / Q000503:physiopathology*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis
D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine