Relationship between asymmetric dimethylarginine [ADMA], proteinuria and endothelial dysfunction in chronic kidney disease

ABSTRACT

The aim of this study was to assess serum asymmetric dimethylarginine [ADMA] and their relation to endothelial dysfunction in chronic kidney disease [CKD] Patients with proteinuria. A total of 54 CKD Patients with normal glomerular filtration rate [GFR] were divided into three groups based on their urinary protein excretion in 24 h 23 patients with nonnephrotic proteinuria [< 3.5 g/d], 17 patients with nephritic-range proteinuria, 14 patients with nephrotic-range proteinuria and secondary amyloidosis [SA] by renal biopsy, in addition to 18 healthy controls. Renal function was estimated with the Cockroft-Gault formula. ADMA was measured by high-performance liquid chromatography [HPLC], assessment of endothelial dysfunction by measuring flow-mediated dilatation [FMD] in brachial artery using high-resolution ultrasound. In addition, high sensitivity C-reactive protein [hsCRP], total cholesterol, triglycerides, high density lipoprotein cholesterol [HDL-C], low density lipoprotein cholesterol [LDL-C], serum albumin and insulin resistance were performed for all patients. The proteinuric patients had higher levels of serum ADMA. hsCRP and insulin resistance. Compared with controls, brachial artery FMD was significantly lower among proteinuric patients, suggesting greater endothelial dysfunction. When patients with secondary amyloidosis were compared with patients with glomerulonephritis who had similar levels of proteinuria, those with amyloidosis had higher ADMA levels and lower FMD measurements. Even after adjusting for confounders, ADMA level correlated with both proteinuria and the presence of secondary amyloidosis, and was an independent predictor of FMD. In conclusion, serum ADMA concentrations were increased in CKD, especially in secondary amyloidosis, and this may explain part of the mechanism by which proteinuria increases cardiovascular morbidity and mortality