Low dialysance of asymmetric dimethylarginine (ADMA) - in vivo and in vitro evidence of significant protein binding

Jt, Kielstein; Rh, Böger; Sm, Bode-Böger; Martens‐Lobenhoffer, Jens; Lonnemann, Gerhard; Jc, Frölich; Haller, Hermann; Fliser, Danilo

doi:10.5414/cnp62295

Cited by 77 publications

(69 citation statements)

References 20 publications

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“…The findings of recent studies, showing no differences in ADMA elimination neither between hemodiafiltration and low-flux HD 17,18 nor among different membrane dialyzers, 18 suggest that plasma proteins that bind ADMA are larger than 40 kDa. 7 Whether ADMA levels reduced in the long-term treatment or modalities with increased convective transport remain to be established.…”

Section: Discussionmentioning

confidence: 99%

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Differences in Bio-incompatibility among Four Biocompatible Dialyzer Membranes Using in Maintenance Hemodialysis Patients

et al. 2011

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Background: Following the introduction of modified cellulosic and then synthetic membrane dialyzers, it was realized that the dialyzer bio-incompatibility depends on the membrane composition. We designed a prospective, randomized, cohort study of 6 months to determine several parameters of biocompatibility in maintenance hemodialysis (MHD) patients treated with four different membrane dialyzers. Methods: There were 60 MHD patients enrolled in the study. In baseline, synthetic low-flux dialyzer, polysulfone (PS) membrane was used in all patients for at least 3 months. Then the patients were randomly divided into three groups according to different dialyzer membranes. Synthetic highflux dialyzer group, ployethersulfone membrane, cellulose triacetate (CTA) high-flux membrane, and synthetic low-flux dialyzer, polymethylmethacrylate (PMMA) membrane were used in 6 months. A new dialyzer was used for each study treatment, and there was no dialyzer reuse. The biocompatibility markers and solutes removal markers were detected repeatedly at different time points. Results: The blood levels of highly sensitive C reactive protein, interleukin (IL)-1β, and interleukin (IL)-13 showed no difference among different groups at al time points. However, the blood complement levels and white blood cell counts were significantly different among three groups. When the dialyzers changed from PS to PMMA membrane, C3a levels and white blood cell counts changed significantly (p < 0.05). Moreover, the changes of C5a levels were significantly different between group CTA and group PMMA in month 3 (p < 0.05). Conclusion: There were much more differences on bio-incompatibility among different dialyzer membranes.

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Section: Discussionmentioning

confidence: 99%

“…Among these parameters, urea, Cr, and UA were regarded as small-molecule solutes, β 2 -microglobulin as a middle molecule solute, and ADMA as a protein-bonded solute. 6,7 The pre-to post-dialysis change in solute concentration was calculated from …”

Section: Measurements Of Solute Removalmentioning

confidence: 99%

Differences in Bio-incompatibility among Four Biocompatible Dialyzer Membranes Using in Maintenance Hemodialysis Patients

et al. 2011

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“…Data conflict as to whether hemodialysis removes ADMA. Most groups report significant removal of ADMA by this modality 60,110,111 whereas Kielstein and colleagues reported low rates of elimination, 112 which they attribute to plasma proteins binding ADMA. Boosting the activity of DDAH enzymes (e.g.…”

Section: Discussionmentioning

confidence: 99%

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

2006

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SummaryNitric oxide (NO) production is reduced in renal disease, partially due to decreased endothelial NO production. Evidence indicates that NO deficiency contributes to cardiovascular events and progression of kidney damage. Two possible causes of NO deficiency are substrate (L-arginine) limitation and increased levels of circulating endogenous inhibitors of NO synthase (particularly asymmetric dimethylarginine [ADMA]). Decreased L-arginine availability in chronic kidney disease (CKD) is due to perturbed renal biosynthesis of this amino acid. In addition, inhibition of transport of L-arginine into endothelial cells and shunting of L-arginine into other metabolic pathways (e.g. those involving arginase) might also decrease availability. Elevated plasma and tissue levels of ADMA in CKD are functions of both reduced renal excretion and reduced catabolism by dimethylarginine dimethylaminohydrolase (DDAH). The latter might be associated with loss-offunction polymorphisms of a DDAH gene, functional inhibition of the enzyme by oxidative stress in CKD and end-stage renal disease, or both. These findings provide the rationale for novel therapies, including supplementation of dietary L-arginine or its precursor L-citrulline, inhibition of non-NOproducing pathways of L-arginine utilization, or both. Because an increase in ADMA has emerged as a major independent risk factor in end-stage renal disease (and probably also in CKD), lowering ADMA concentration is a major therapeutic goal; interventions that enhance the activity of the ADMA-hydrolyzing enzyme DDAH are under investigation.

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“…8 ADMA is a residue of proteolysis of arginine-methylated pro- teins, and it is a potent inhibitor of nitric oxide synthesis. 9 It is cleared by the kidney in vivo, and is found in elevated circulating levels in CKD. 9 We recently reported that nondiabetic proteinuria is associated with elevation of ADMA in CKD.…”

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confidence: 99%

“…9 It is cleared by the kidney in vivo, and is found in elevated circulating levels in CKD. 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.…”

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confidence: 99%

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

Yılmaz¹,

Sönmez²,

Sağlam³

et al. 2008

Journal of the American Society of Nephrology

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Asymmetric dimethyl-arginine (ADMA), a residue of the proteolysis of arginine-methylated proteins, is a potent inhibitor of nitric oxide synthesis. The increased protein turnover that accompanies proteinuric secondary amyloidosis may increase circulating levels of ADMA, and this may contribute to endothelial dysfunction. We performed a cross-sectional study of 121 nondiabetic proteinuric patients with normal GFR (including 39 patients with nephrotic-range proteinuria and secondary amyloidosis) and 50 age-, sex-, and BMI-matched healthy controls. The proteinuric patients had higher levels of serum ADMA, symmetric dimethyl-arginine (SDMA), high-sensitivity C-reactive protein (hsCRP), and insulin resistance (homeostasis model assessment index) than controls. Compared with controls, brachial artery flow-mediated dilatation (FMD), serum L-Arginine, and the L-Arginine/ADMA ratio were 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 and SDMA levels and lower L-Arginine/ADMA ratios and FMD measurements (P Ͻ 0.001 for all). Finally, even after adjusting for confounders, ADMA level correlated with both proteinuria and the presence of secondary amyloidosis, and was an independent predictor of FMD. We propose that ADMA synthesis may be increased in chronic kidney disease, especially in secondary amyloidosis, and this may explain part of the mechanism by which proteinuria increases cardiovascular morbidity and mortality.

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Low dialysance of asymmetric dimethylarginine (ADMA) - in vivo and in vitro evidence of significant protein binding

Cited by 77 publications

References 20 publications

Differences in Bio-incompatibility among Four Biocompatible Dialyzer Membranes Using in Maintenance Hemodialysis Patients

Differences in Bio-incompatibility among Four Biocompatible Dialyzer Membranes Using in Maintenance Hemodialysis Patients

Arginine, arginine analogs and nitric oxide production in chronic kidney disease

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

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