ADMA, proteinuria, and insulin resistance in non-diabetic stage I chronic kidney disease

Abstract

The rationale of this study is based on the fact that, both proteinuria and elevated asymmetric dimethyl arginine (ADMA) levels have been linked to the progression of vascular disease. Currently, there is not enough knowledge about any association between the levels of proteinuria and ADMA levels. Seventy-eight non-diabetic patients (42 men, 36 women, mean age of 26.1+/-5.2 years) with proteinuria having normal glomerular filtration rate were enrolled along with 38 healthy subjects (20 men, 18 women, mean age of 26.9+/-5.9 years). Proteinuria was below 3.5 g/day in 40 patients and above 3.5 g/day in 38 patients. Both groups had similar age, gender, and body mass index distributions. Serum ADMA, symmetric dimethyl arginine (SDMA), immunoreactive insulin, and high sensitivity C reactive protein (hsCRP) levels were measured. Insulin resistance was determined by homeostasis model assessment (HOMA). Serum ADMA, SDMA, insulin, hsCRP levels, and HOMA indexes were significantly higher in patients than in healthy control subjects. The above parameters were higher in the nephrotic range proteinuria group when compared to patients having protein levels below 3.5 g/day. There were significant correlations between the levels of proteinuria and the above parameters. According to the regression analysis, levels of proteinuria and hsCRP were significant determinants of serum ADMA levels. Our results indicate that, independent of other risk factors, ADMA is directly associated with proteinuria. Further studies are recommended to find out whether elevated ADMA levels are implicated in the high cardiovascular risk of proteinuric nephropathies.

Inflammation and Asymmetric Dimethylarginine for Predicting Death and Cardiovascular Events in ESRD Patients

“…Both dialysis-related and dialysis-independent factors may promote inflammation by stimulating the synthesis and/or release of several pro-inflammatory cytokines like CRP, IL-1, IL-6, TNF-␣, and IFN-␥ (23). Impaired endothelium-dependent vasodilation is a hallmark in patients with ESRD (31), and high ADMA levels are considered as a major factor in endothelial dysfunction in chronic renal failure (31,32). In our study, the majority of ESRD patients had circulating levels of ADMA and CRP above the corresponding upper limit of the normal range (59% and 55%, respectively).…”

ADMA Levels Correlate with Proteinuria, Secondary Amyloidosis, and Endothelial Dysfunction

“…14,15 Because the kidneys provide a significant route for clearance of methylarginines, 16,17 it is perhaps not surprising that ADMA 18 and SDMA concentrations increase in CKD patients even without proteinuria, 19,20 or that proteinuria with reduced renal function is associated with both elevated ADMA and endothelial dysfunction. 10,21,22 However, the patients in our study all had a nearly normal renal function. Inflammation, defined here as an elevated serum hsCRP, is also known to influence ADMA and has been proposed to be one factor linking ADMA to CVD.…”

“…9 We recently reported that nondiabetic proteinuria is associated with elevation of ADMA in CKD. 10 In this study, we hypothesized that this might be the result of an abnormal protein turnover in proteinuria, which might be further exacerbated in SA. We furthermore hypothesized that an ADMA-associated endothelial dysfunction would be yet another factor linking proteinuric CKD to an increase in cardiovascular risk.…”

Coronary Artery Calcification, ADMA, and Insulin Resistance in CKD Patients

“…Recently, it has been reported that the patients with proteinuria have higher ADMA levels along with impaired insulin sensitivity (35). Increased ADMA appears to be a potential link between proteinuria and endothelial dysfunction and atherosclerotic complications.…”