Asymmetric dimethylarginine compartmental behavior during high-flux
hemodialysis

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Abstract

Aim

The accumulation of uremic toxins, such as asymmetric dimethylarginine (ADMA), has emerged as one of the major cardiovascular disease-related risk factors in patients with end-stage renal disease (ESRD). Based on the low molecular weight of ADMA, hemodialysis (HD) should theoretically effectively remove ADMA. In this study, we investigated the clearance behavior of ADMA during high-flux HD.

Methods

Eight HD patients without residual renal function were included. Blood samples were collected at 0, 30, 60, 120 and 240 min after dialysis started, as well as 1 h and 48 h after dialysis. ADMA level was detected by HPLC-MS/MS. Herein, the ADMA level in blood cells and the ADMA protein binding rate were measured. Accordingly, the dialyzer extraction ratio was also determined.

Results

The reduction ratio (RR) of ADMA (corrected for hemoconcentration) was significantly lower, at only 37.21 ± 6.44%, than that of urea and creatinine ( p < .05). Interestingly, its clearance from plasma was precipitous early in dialysis and became slowly from 60 to 240 min. Additionally, a greater inlet erythrocyte than plasma concentration was found for ADMA. The dialyzer extraction ratio was comparable between ADMA and creatinine or urea (83 ± 5% for ADMA vs. 84 ± 3% and 88 ± 2% for creatinine and urea, respectively; both p>.05). Urea and creatinine had a slight rebound ratio of less than 10% at 1 h after the completion of HD. In contrast, considerable rebound of approximately 30% was detected in ADMA.

Conclusion

This study suggests that ADMA may present a multicompartmental distribution that cannot be representatively reflected by the urea kinetics model.

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Most cited references 29

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Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study.

C Zoccali, S Bode-Böger, F Mallamaci … (2015)

The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric-oxide synthase, which has been linked to endothelial dysfunction and atherosclerosis in the general population, is raised in patients with end-stage renal disease and could contribute to the high cardiovascular risk in patients with chronic renal failure. We investigated the relation between cardiovascular risk factors and plasma ADMA concentration in a cohort of haemodialysis patients (n=225), and tested the predictive power of ADMA for mortality and cardiovascular outcomes. Patients had standard dialysis three times a week. We accurately recorded cardiovascular events over a mean follow-up of 33.4 months (SD 14.6); these events were reviewed by a panel of physicians. We identified correlates of plasma ADMA by univariate and multivariate analyses. On univariate analysis, ADMA concentration in plasma was directly related to concentrations of fibrinogen and L-arginine in plasma, duration of dialysis treatment, and serum cholesterol concentration, and was inversely related to serum albumin concentration. On multivariate analysis, only plasma fibrinogen (p=0.0001) and serum albumin (p=0.04) concentrations were independently related to plasma ADMA concentration (multiple r=0.44, p=0.0001). 83 patients died, 53 (64%) by cardiovascular causes. In a Cox's proportional-hazards model, plasma ADMA ranked as the second factor predicting overall mortality (hazard ratio 1.26, 95% Cl 1.11-1.41, p=0.0001) and cardiovascular events (1.17, 1.04-1.33, p=0.008). In haemodialysis patients, plasma ADMA is a strong and independent predictor of overall mortality and cardiovascular outcome. These findings lend support to the hypothesis that accumulation of ADMA is an important risk factor for cardiovascular disease in chronic renal failure.

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Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly Patients

Jan Elting, Casper F.M. Franssen, Carlo A.J.M. Gaillard … (2018)

The initiation of hemodialysis is associated with an accelerated decline of cognitive function and an increased incidence of cerebrovascular accidents and white matter lesions. Investigators have hypothesized that the repetitive circulatory stress of hemodialysis induces ischemic cerebral injury, but the mechanism is unclear. We studied the acute effect of conventional hemodialysis on cerebral blood flow (CBF), measured by [ 15 O]H 2 O positron emission tomography–computed tomography (PET-CT). During a single hemodialysis session, three [ 15 O]H 2 O PET-CT scans were performed: before, early after the start of, and at the end of hemodialysis. We used linear mixed models to study global and regional CBF change during hemodialysis. Twelve patients aged ≥65 years (five women, seven men), with a median dialysis vintage of 46 months, completed the study. Mean (±SD) arterial BP declined from 101±11 mm Hg before hemodialysis to 93±17 mm Hg at the end of hemodialysis. From before the start to the end of hemodialysis, global CBF declined significantly by 10%±15%, from a mean of 34.5 to 30.5 ml/100g per minute (difference, −4.1 ml/100 g per minute; 95% confidence interval, −7.3 to −0.9 ml/100 g per minute; P =0.03). CBF decline (20%) was symptomatic in one patient. Regional CBF declined in all volumes of interest, including the frontal, parietal, temporal, and occipital lobes; cerebellum; and thalamus. Higher tympanic temperature, ultrafiltration volume, ultrafiltration rate, and pH significantly associated with lower CBF. Thus, conventional hemodialysis induces a significant reduction in global and regional CBF in elderly patients. Repetitive intradialytic decreases in CBF may be one mechanism by which hemodialysis induces cerebral ischemic injury.

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Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis.

G Hercz, A Pierratos, I Mucsi … (1998)

We compared the efficacy and the long-term effects of nocturnal hemodialysis (NHD) versus conventional hemodialysis (CHD) in controlling serum phosphate levels in patients with end-stage renal disease (ESRD). Patients underwent thrice weekly CHD and were subsequently switched to NHD six nights weekly. In the "acute" study serum and dialysate phosphate were measured during and after dialysis, and the total dialysate was collected to calculate mass solute removal. Although pre-dialysis (1.7 +/- 0.6 vs. 1.5 +/- 0.8 mM) serum phosphate levels were similar in CHD and NHD, respectively, post-dialysis levels were slightly lower with CHD (0.7 +/- 0.2 vs. 0.8 +/- 0.2 mM, P < 0.05). The measured phosphate removed per session of CHD or NHD was comparable, 25.3 +/- 7.5 versus 26.9 +/- 9.8 mumol/session, respectively. On the other hand, the cumulative weekly phosphate removal was significantly higher with NHD as compared to CHD, 75.8 +/- 22.5 versus 161.6 +/- 59.0 mumol/week (P < 0.01). In the "chronic" study serum phosphate levels were measured monthly for five months on CHD and for five months after the patients were switched to NHD. Dietary phosphate intake and the dosage of phosphate binders were tabulated. Serum phosphate levels fell during NHD: 2.1 +/- 0.5 mM at the beginning of the study and 1.3 +/- 0.2 mM five months after being switched to NHD (P < 0.001). At the same time dietary phosphate intake increased by 50%. By the fourth month of NHD therapy none of the patients was taking any phosphate binders. In conclusion, NHD is more effective in controlling serum phosphate levels than CHD, allowing patients to discontinue their phosphate binders completely and to ingest a more liberal diet.

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Author and article information

Journal

Journal ID (nlm-ta): Ren Fail

Journal ID (iso-abbrev): Ren Fail

Title: Renal Failure

Publisher: Taylor & Francis

ISSN (Print): 0886-022X

ISSN (Electronic): 1525-6049

Publication date (Electronic, pub): 30 July 2020

Publication date (Electronic, collection): 2020

Volume: 42

Issue: 1

Pages: 760-766

Affiliations

[a ]Department of Nephrology, Tongji Hospital, Tongji University School of Medicine , Shanghai, China

[b ]Department of Nephrology, Renji Hospital, Shanghai Jiaotong University School of Medicine , Shanghai, China

Author notes

CONTACT Qiuna Du duqiuna2015@ 123456163.com Department of Nephrology, Tongji Hospital, Tongji University School of Medicine , 389 Xincun Road, Putuo District, Shanghai, 200065, CN, China;

Yucheng Yan yucheng.yan@ 123456163.com Department of Nephrology, Renji Hospital, Shanghai Jiaotong University School of Medicine , No.1630, Dongfang Road, Pudong New Area, Shanghai, CN, 200127China

Article

Publisher ID: 1797790

DOI: 10.1080/0886022X.2020.1797790

PMC ID: 7470094

PubMed ID: 32727241

SO-VID: 864d6372-f915-46f4-8c04-1efa6d121aac

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Asymmetric dimethylarginine compartmental behavior during high-flux hemodialysis

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Abstract

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Methods

Results

Conclusion

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Karger: Nephrology

Most cited references 29

Plasma concentration of asymmetrical dimethylarginine and mortality in patients with end-stage renal disease: a prospective study.

Hemodialysis Induces an Acute Decline in Cerebral Blood Flow in Elderly Patients

Control of serum phosphate without any phosphate binders in patients treated with nocturnal hemodialysis.

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