Concentration of dimethyl-L-arginine in the plasma of patients with end-stage renal failure

Abstract

Abstract. NGNG dimethyl-L-arginine (asymmetric dimethyl-L-arginine; ADMA) and NGNG dimethyl-L-arginine (symmetric dimethyl-L-arginine; SDMA) are naturally occurring analogues of L-arginine, the substrate for nitric oxide (NO) synthesis. ADMA is a potent inhibitor of NO synthesis, and accumulates in the plasma of patients with renal failure. However the precise concentration of ADMA and SDMA in renal patients is still controversial. This study was performed to measure plasma ADMA and SDMA concentrations by two different HPLC techniques in nine healthy controls and 10 uraemic subjects, and to investigate the effects of haemodialysis. In controls, the mean (+/-SEM) plasma concentrations of ADMA and SDMA were 0.36 +/- 0.09 and 0.39 +/- 0.05 mumol/l respectively, yielding an ADMA/SDMA ratio of 1.2 +/- 0.17. In uraemic patients, the plasma concentrations of ADMA and SDMA were 0.9 +/- 0.08 mumol/l (P < 0.001 compared to controls) and 3.4 +/- 0.3 mumol/l (P < 0.001 compared to controls) with an ADMA/SDMA ratio of 0.27 +/- 0.015 (P < 0.001). In the course of one 4 h haemodialysis session, ADMA concentrations decreased from 0.99 +/- 0.13 to 0.77 +/- 0.3 mumol/l and SDMA concentrations from 3.38 +/- 0.44 to 2.27 +/- 0.21 mumol/l. The plasma ADMA/creatinine ratio tended to increase from 1.26 +/- 0.20 x 10(-3) to 2.01 +/- 0.41 x 10(-3). It is concluded that there is a modest (3-fold) but definite increase in plasma ADMA concentration in uraemic patients compared to controls. SDMA accumulates to a greater degree (8-fold increase) and more closely parallels creatinine concentration than ADMA. The change in the ADMA/SDMA ratio is not accounted for by greater renal or dialysis clearance of ADMA, and, even though alternative explanations are not excluded, greater metabolism of ADMA than SDMA is the most likely explanation. Although small in magnitude, the increase in ADMA concentration might by biologically significant.

Developmental changes in the L-arginine/nitric oxide pathway from infancy to adulthood: plasma asymmetric dimethylarginine levels decrease with age

“…This lack of data makes it difficult to assess changes of these parameters, and thus of the status of the L-arginine/NO pathway under pathophysiological conditions including inborn diseases, such as citrullinemia (32) or Schimke-immuno-osseous dys- plasia (33). In our opinion, there is a need to establish comprehensive reference data for infants, children, teenagers and adolescents since the L-arginine/NO pathway is involved in the pathogenesis of different pathological states, e.g., renal (7,(14)(15)(16)(17) and cardiovascular (18-23) diseases or hyperlipidemia (26,34).…”

“…In various disorders, notably renal (7,(14)(15)(16)(17) and cardiovascular (18)(19)(20)(21)(22)(23) diseases, biosynthesis and bioavailability of NO are compromised. Infusion of ADMA in healthy adults has been shown to exert adverse effects on cardiovascular and renal function at blood concentrations similar to those found in patients with cardiovascular pathology wreviewed in ref.…”

Nitric Oxide Production Is Reduced in Patients With Chronic Renal Failure

“…23 Alternatively, impaired NO production may also have resulted from accumulation of the endogenous NOS-inhibitor ADMA in patients with end-stage renal disease, which is well documented. [7][8][9] Furthermore, the bioavailability of the NOS substrate L-arginine has been found to be decreased in subtotally nephrectomized rats 10,11 as well as in dialysis patients, possibly as a result of malnutrition or arginine loss caused by hemodialysis. 12 In the present study, plasma L-arginine levels of the CRF patients also tended to be lower than that of the other groups, although the differences were not significant.…”

“…6,7 However, the finding of a reduced NO bioavailability as demonstrated by functional studies does not provide insight into the mechanisms causing endothelial dysfunction, because reduced bioavailability can be the result of decreased NO production, increased NO degradation, or both. In patients with CRF, NO production can be reduced by a diminished NO synthase (NOS) activity, which in turn can be the result of a decreased clearance of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA), [7][8][9] or a decreased bioavailability of the NOS substrate L-arginine. 10 -12 On the other hand, CRF has also been associated with enhanced concentrations of oxygen radical species that can inactivate NO.…”

Reduced production of nitric oxide during haemodialysis

“…Renal failure is often accompanied by hypertension, and interestingly, patients with renal failure have been shown to possess high levels of guanidinosubstituted analogues of l-arginine compounds that inhibit NO synthesis. [5][6][7] Since guanidino compounds can be removed by dialysis, 8 their serum levels should decrease after haemodialysis in uraemic patients. In contrast to the hypertensionrelated effects of NO, overproduction of NO due to cantly by the end of haemodialysis (42 ؎ 26 M).…”