Guanidino compounds in serum and urine of nondialyzed patients with chronic renal insufficiency

Marescau, Bart; Nagels, Guy; Possemiers, Ilse; Broe, Marc E. De; Becaus, I.; Billiouw, Jean-Marie; Lornoy, W.; Deyn, Peter Paul De

doi:10.1016/s0026-0495(97)90273-0

Cited by 163 publications

(156 citation statements)

References 32 publications

Supporting

Mentioning

131

Contrasting

Unclassified

Order By: Relevance

“…9 If plasma ADMA levels increase and arginine levels are unchanged or decrease, NOS should be inhibited, as suggested by Vallance et al 9 Not all investigators agree, however, that plasma ADMA levels increase sufficiently in ESRD to have an impact on NOS activity. 10,24,25 In the present study, however, we observed marked increases in plasma ADMA levels in uremia to values that, although less than originally reported, 9 are sufficient to exert some NOS inhibitory effect. Therefore, although this area remains controversial, the present study supports the possibility that an increase in the ADMAarginine ratio contributes to NO deficiency in patients with ESRD.…”

Section: Discussioncontrasting

confidence: 70%

Indices of activity of the nitric oxide system in hemodialysis patients

Schmidt

Domico

Samsell

et al. 1999

American Journal of Kidney Diseases

102

View full text Add to dashboard Cite

Arginine deficiency and/or increased levels of circulating nitric oxide (NO) synthesis (NOS) inhibitors can cause reduced NOS, which may contribute to hypertension in patients with end-stage renal disease (ESRD). To test these hypotheses, NO oxidation products (NO 2 + NO 3 = NO x ) and cyclic guanosine monophosphate (cGMP), the vasodilatory second messenger of NO, were measured in the blood, urine, and dialysate effluent of hemodialysis (HD) patients and compared with the blood and urine of healthy subjects. The subjects ate a controlled low-nitrate diet (∼330 μmol/d) for 48 hours before and during blood, dialysis effluent, and 24-hour urine collection. NO x output was significantly reduced in HD patients versus controls (552 ± 51 v 824 ± 96 μmol/24 h; P < 0.001), whereas cGMP output was not low versus controls. Plasma arginine level was normal and plasma levels of citrulline and the endogenous NOS inhibitor, asymmetric dimethylarginine (ADMA), were markedly elevated in patients with ESRD versus controls. Systolic blood pressure was greater in HD patients compared with controls despite concurrent antihypertensive therapy in most patients with ESRD. These studies suggest NO production is low in patients with ESRD undergoing HD, possibly because of the increased ratio of plasma ADMA to arginine. Index WordsEnd-stage renal disease; hypertension; arginine; cyclic guanosine monophosphate (cGMP); endogenous nitric oxide synthases (NOS) inhibitors Nitric oxide (NO) is a potent vasodilator made from L-arginine by the enzymatic action of several widely distributed nitric oxide synthases (NOSs). The constitutively expressed, vascular endothelial and brain-type NOSs have major roles in the physiological control of vascular tone and kidney function, and many of these actions are mediated by cyclic guanosine monophosphate (cGMP). 1,2 NO deficiency can be produced experimentally by the administration of substituted L-arginine analogues that function as competitive inhibitors of NOS. Chronic experimental NOS inhibition in animals produces hypertension, and NOS may be defective in some individuals with primary and secondary hypertension. 3 Hypertension is particularly prevalent in hemodialysis (HD) patients with end-stage renal disease (ESRD), 4-7 and there are valid reasons to suspect NO deficiency might occur and contribute to the hypertension in this population. We previously reported that patients with ESRD undergoing peritoneal dialysis (PD) produce less NO, indicated by the removal rate of the stable inert oxidation products of NO (NO 2 In addition, the plasma levels of naturally occurring compounds that inhibit the L-arginine-NO pathway accumulate in patients with ESRD. For example, plasma levels of asymmetric dimethylarginine (ADMA) increase in HD patients, possibly to concentrations that inhibit NOS, although this remains controversial. 9,10 This, together with plasma arginine levels in the low-normal range, 9,11 means the ratio of plasma levels of endogenous NOS inhibitors to Larginine is high in patients wit...

show abstract

Section: Discussioncontrasting

confidence: 70%

Indices of activity of the nitric oxide system in hemodialysis patients

Schmidt

Domico

Samsell

et al. 1999

American Journal of Kidney Diseases

102

View full text Add to dashboard Cite

show abstract

“…51 However, the existence of trans-aconitate in mammals, its biological effects, and its precise role in renal failure has not been clarified, although ADMA and GSA are well-known uremic toxins. [52][53][54][55] Furthermore, trans-aconitate was identified as the uremic toxin inducing superoxide and hypertension through both in vitro and in vivo studies. It also was confirmed by CE-MS analysis of 41 CKD patients that not only ADMA and GSA, but also transaconitate, exists in human beings and that their concentrations are increased in accordance with CKD progression.…”

Section: Role Of Oatp4c1 In Uremic Toxin Clearancementioning

confidence: 99%

The Kidney and Uremic Toxin Removal: Glomerulus or Tubule?

Masereeuw

Mutsaers

Toyohara³

et al. 2014

Seminars in Nephrology

133

122

View full text Add to dashboard Cite

This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues.Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited.

show abstract

“…Only ADMA but not SDMA is metabolized by dimethylarginine dimethylaminohydrolase to citrulline and dimethylamine (15). SDMA seems to be strictly eliminated by renal excretion (16,17). A recent study by Fliser et al (18) showed a very close correlation among serum creatinine, GFR (measured by iodothalamate clearance technique), and SDMA.…”

mentioning

confidence: 97%

Symmetrical Dimethylarginine

Bode‐Böger

Scalera

Kielstein

et al. 2006

Journal of the American Society of Nephrology

253

204

View full text Add to dashboard Cite

Symmetrical dimethylarginine (SDMA) is the structural isomer of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine. Whereas the major route of asymmetric dimethylarginine elimination is the hydrolytic degradation by dimethylarginine dimethylaminohydrolase, SDMA is eliminated by renal excretion. SDMA does not directly inhibit NOS but is a competitor of arginine transport. This study showed for the first time that measurement of SDMA can be a marker of estimated GFR and extent of coronary artery disease (CAD). In 97 patients with CAD, SDMA was a marker of estimated GFR. On multiple regression analysis of the CAD parameter stenosis score, SDMA was the only parameter retained. In addition, endothelial cells from the third passage were cultured in medium that contained 70 mol/L arginine and was incubated for 24 h in the presence of various concentration of SDMA (0, 2, 5, 10, and 100 mol/L). The levels of nitrate and nitrite in conditioned media, the protein expression of NOS, and the content of reactive oxygen species in endothelial cells were determined. SDMA inhibited dose dependently the NO synthesis in intact endothelial cells, whereas it had no effect on protein expression of NOS. This effect was associated with an increase in reactive oxygen species. Co-incubation with S ymmetrical dimethylarginine (SDMA) is the structural isomer of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA). ADMA has been shown to correlate with risk factors for coronary artery disease (CAD) such as hypertension (1,2), hypercholesterolemia (3), hyperhomocysteinemia (4 -6), insulin resistance (7), age (1), and mean arterial pressure (1). Moreover, ADMA correlates with the extent and the severity of coronary atherosclerosis (8) and is a strong and independent marker of cardiovascular events and mortality in selected patient populations (9 -11). Although there is mounting evidence that chronically elevated ADMA may contribute to progression of vascular disease via endothelial damage, little attention has been paid to the role of SDMA. Both ADMA and SDMA derive from intranuclear methylation of l-arginine residuals and are released into the cytoplasm after proteolysis (12). SDMA is produced by protein-arginine methyltransferase 5 (PRMT 5) and PRMT 7 (both type II methyltransferases) (13,14). Only ADMA but not SDMA is metabolized by dimethylarginine dimethylaminohydrolase to citrulline and dimethylamine (15). SDMA seems to be strictly eliminated by renal excretion (16,17). A recent study by Fliser et al. (18) showed a very close correlation among serum creatinine, GFR (measured by iodothalamate clearance technique), and SDMA. The authors speculated that SDMA, equal to serum creatinine, can serve as a marker of renal function, but SDMA seems to be more than a simple indicator of renal function. In animals, a high-fat, high-cholesterol diet increases SDMA serum levels (19,20) without affecting renal function (20), indicating that cardiovascular risk factors other than impaired...

show abstract

Guanidino compounds in serum and urine of nondialyzed patients with chronic renal insufficiency

Cited by 163 publications

References 32 publications

Indices of activity of the nitric oxide system in hemodialysis patients

Indices of activity of the nitric oxide system in hemodialysis patients

The Kidney and Uremic Toxin Removal: Glomerulus or Tubule?

Symmetrical Dimethylarginine

Contact Info

Product

Resources

About