Effect of haemodiafiltration with online regeneration of ultrafiltrate on oxidative stress in dialysis patients.
BACKGROUND
Increased oxidative stress (OxSt) as well as inflammation are risk factors for cardiovascular events and determinant of cardiovascular disease which remains the most common cause of excess morbidity and mortality for end-stage renal disease ESRD patients. Haemodiafiltration with on-line regeneration of ultrafiltrate (HFR) has been shown to have a positive impact on markers of inflammation while its effect on OxSt is not known.


METHODS
This study evaluates in haemodialysis patients the effect of HFR on the plasma level of oxidized LDL (OxLDL), a marker of OxSt, and mononuclear cell gene and protein expression of OxSt-related proteins such as p22phox (subunit of NAD(P)H oxidase), PAI-1 (induced by OxSt and atherothrombogenetic) and haeme-oxygenase-1 (HO-1) (induced by OxSt). Fourteen patients were randomized into two groups in a crossover design, treated for 6 month periods with HFR (SG8 Plus-Bellco, Mirandola, Italy) or low-flux bicarbonate dialysis (HD) using a polysulphone dialyser 1.8 m2. Blood samples were collected at the beginning of the study, after 6 months (crossover) and after 12 months.


RESULTS
ANOVA analysis of the data performed to rule out any crossover effect in either sequence was not significant and thus data from both sequences were combined and then analysed further statistically. HFR reduced mRNA production and protein expression of p22phox and PAI-1 compared with HD (-9+/-5 vs 2+/-6 Delta%, P<0.0001 and -15+/-20 vs 3+/-17 Delta%, P<0.05 for p22phox; -19+/-6 vs -5+/-5 Delta%, P<0.0001 and -24+/-12 vs 9+/-15 Delta%, P<0.0001 for PAI-1). HO-1 was unchanged (-12+/-8 vs -10+/-8 Delta% and -21+/-12 vs -14+/-8 Delta%) while plasma OxLDL was reduced (-14+/-19 vs 1+/-14 Delta%, P<0.01).


CONCLUSIONS
The results of our study indicate that HFR treatment, compared with standard dialysis, has a lower impact on OxSt. Given, the strong relationship between OxSt and inflammation and their impact on the long-term cardiovascular complications in end-stage renal disease patients, HFR might have a more beneficial impact in reducing the risk of atherosclerotic cardiovascular disease in dialysis patients.
Calò
Lorenzo A
LA
Department of Clinical and Experimental Medicine, Clinica Medica 4, University of Padova-Azienda Ospedaliera Padova, Via Giustiniani, 2, 35128 Padova, Italy. renzcalo@unipd.it
Naso
Agostino
A
Carraro
Gianni
G
Wratten
Mary Lou
ML
Pagnin
Elisa
E
Bertipaglia
Lara
L
Rebeschini
Mirka
M
Davis
Paul A
PA
Piccoli
Antonio
A
Cascone
Carmelo
C
D000328:Adult; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D018592:Cross-Over Studies; D005260:Female; D005786:Gene Expression Regulation; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D017583:Hemodiafiltration / Q000379:methods*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods*; D012307:Risk Factors; D014462:Ultrafiltration / Q000379:methods*
D008077:Lipoproteins, LDL; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases; C086986:CYBA protein, human