Asymmetric Dimethylarginine Plasma Concentrations Differ in Patients with End-Stage Renal Disease

Abstract

Abstract. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Its concentration is elevated in patients with end-stage renal disease (ESRD), in part because it is excreted via the kidneys. In this study, the plasma concentrations of ADMA, symmetric dimethylarginine, and L-arginine were determined in relation to plasma nitrate levels (as an index of NO formation) for a group of 80 patients with ESRD. The effects of two treatment methods, i.e., hemodialysis (HD) and peritoneal dialysis (PD), and the role of the presence of atherosclerotic disease were evaluated. Forty-three patients receiving HD and 37 patients receiving PD were compared with healthy control subjects. Plasma L-arginine and dimethylarginine levels were determined by HPLC, using precolumn derivatization with o-phthaldialdehyde. Plasma nitrate levels were determined by gas chromatography-mass spectrometry. Predialysis ADMA concentrations in HD-treated patients were approximately sixfold higher than those in the control group (6.0 ± 0.5 versus 1.0 ± 0.1 μmol/L; P < 0.05). Plasma nitrate concentrations were significantly lower in HD-treated patients, which suggests that ADMA may inhibit NO synthase. In contrast, plasma ADMA levels and nitrate concentrations in PD-treated patients were similar to those in control subjects. Plasma L-arginine concentrations were not significantly decreased in patients with ESRD. ADMA concentrations were significantly decreased 5 h after HD, compared with baseline values. ADMA levels were significantly higher in HD-treated patients with manifest atherosclerotic disease than in HD-treated patients without atherosclerotic disease (7.31 ± 0.70 versus 3.95 ± 0.52 μmol/L; P < 0.05). This study confirms that ADMA is accumulated in ESRD. PD-treated patients exhibit significantly lower ADMA levels than do HD-treated patients. Accumulation of ADMA may be a risk factor for the development of endothelial dysfunction and cardiovascular disease in patients with ESRD.

The Role of Symmetrical and Asymmetric Dimethyl-L-Arginine as Biomarkers in Dialysis-Dependent Aki Patients

“…Another trial on preclinical models discovered a link between SDMA levels and creatinine clearance. Kielstein et al reported that SDMA levels increased by more than 400% when relative to our data (27). On the other hand, Leone et al, reported a similar (up to four-fold) increase in the construction of both ADMA and SDMA, however, their study was limited to following up only 15 volunteers (6 controls and 9 hemodialysis patients) (23).…”

CE-MS-Based Identification of Uremic Solutes Specific to Hemodialysis Patients

“…Although not statistically significant, the serum glutamate levels showed a tendency to increase after HD in our study (removal rate: −28.5%; Figure 2 ). In addition, it has been reported that the plasma ADMA concentration increased 1 h after HD compared to before HD, and decreased significantly 5 h after HD compared to 1 h after HD [ 30 ]. The authors speculated that the increase in the ADMA levels after HD could be partly the result of a redistribution of tissue ADMA into the plasma compartment during HD [ 30 ].…”

“…In addition, it has been reported that the plasma ADMA concentration increased 1 h after HD compared to before HD, and decreased significantly 5 h after HD compared to 1 h after HD [ 30 ]. The authors speculated that the increase in the ADMA levels after HD could be partly the result of a redistribution of tissue ADMA into the plasma compartment during HD [ 30 ]. Similarly, there could be a possibility that the distribution from the tissue into the serum compartment during HD affected the removal rates analyzed in this study.…”

“…As we previously reported [8], non-HD CKD patients consisted of 41 patients whose estimated glomerular filtration rate (eGFR) was below 60 mL/min/1.73 m 2 . The numbers of patients in CKD stage G3 (30 ≤ eGFR <60), G4 (15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) and G5 (<15) were 11, 17 and 13, respectively. The characteristics of CKD stage G5 patients are also shown in Table 1.…”

Hypertension in chronic kidney disease: What lies behind the scene

“…It is also reported to be elevated in CKD ( Leone et al, 1992 ; Fleck et al, 2001 ) and ESRD patients on dialysis ( Anderstam et al, 1997 ). Interestingly, ADMA levels have been found to correlate with the severity of atherosclerosis ( Kielstein et al, 1999 ), CV events, and mortality in CKD patients ( Zoccali et al, 2001 ), and even with renal disease state progression ( Fliser et al, 2005 ). Asymmetric dimethylarginine levels can be influenced by Ang II through the activation of AT 1 receptors; thus, Ang II can indirectly predispose to further NOS inhibition ( Palm et al, 2007 ), perpetuating to eNOS uncoupling with free radicals generation ( Vallance and Leiper, 2004 ).…”