| Background and objectiveUric acid(UA) is the final product of purine catabolism in humans.In most other mammals,UA is further oxidized to a more soluble allantoin by the enzyme urate oxidase which is not present in humans.UA is formed primarily in the liver.About two thirds of UA is excreted by the kidney,and the rest is eliminated by the gastrointestinal tract.An increase in serum UA results from the overproduction, impaired excretion,or combined mechanisms.In humans,about half the antioxidant capacity of plasma comes from UA. Whereas UA is a strong reducing agent and potent antioxidant,it is also pro-oxidative under certain conditions,especially when other antioxidants are at low levels. Hyperuricemia has been shown associated with increased cardiovascular mortality and is a risk factor for cardiovascular events.In the paper published in 1879 that originally described essential hypertension,Frederick Akbar Mohamed noted that many of his subjects came from gouty families.He hypothesized that uric acid might be integral to the development of essential hypertension.Ten years later,this hypothesis reemerged when Haig proposed low-purine diets as a means to prevent hypertension and vascular disease.It is interesting that the development of arteriolosclerosis can be prevented using allopurinol to control uric acid levels; however,hydrochlorothiazide,which normalizes BP without lowering serum uric acid, does not prevent the development of arteriolosclerosis,indicating that uric acid,not hypertension,is the causative stimulus.Vascular endothelial cells play an important role in maintaining cardiovascular homeostasis and cardiovascular events are always triggered by endothelial dysfunction.Endothelial function has been assessed in humans both invasively and non-invasively.The current standard for noninvasive assessment of endothelial function is the flow-mediated dilatation(FMD) test which has significant advantages in studying clinical populations.To date,the relationship of UA to endothelial dysfunction has been evaluated in a group of essential hypertensive patients but not in CKD population and the development of arteriolosclerosis can be prevented using allopurinol to control uric acid levels.In the present study,we aimed to investigate the possible link of UA with endothelial function and the effect of treatment of hyperuricemia with allopurinol on endothelial function in a group of peritoneal dialysis patients,Methods1.In this cross-sectional study,the relationship of UA and endothelial dysfunction was investigated in 189 stable PD patients.The clinical and laboratory data were collected.Endothelial function was estimated by flow-mediated dilatation (FMD) of the brachial artery and expressed as percentage change relative to baseline diameter.2.In this randomize controlled trial,a total of 113(75 hyperuricemia and 38 normal uric acid) individuals were included.Hyperuricemia individuals were divided into test(38 individuals) and control(37 individuals) groups randomly.38 patients in test group with serum uric acid levels≥420μmol/L(19 women,19 men) were treated with allopurinol 200mg/day for one month.Individuals in control and normal uric acid groups were not treated with allopurinol.Patients and normal uric acid subjects were examined at baseline and after one month of therapy with allopurinol(200 mg/day) in test group.Results1.Cross-sectional study:UA levels did not differ between 93 male and 96 female patients(416.31±86.93 vs 395.52±87.47μmol/L,p＞0.05).Patients were grouped into 3 tertiles on the basis of their serum UA levels.Systolic blood pressure(SBP) (p=0.007),serum phosphate(p=0.005),high sensitive C-reactive protein(hs-CRP) (p＜0.001),and FMD(p=0.016) were all different among UA tertiles.FMD was found to be related with UA(p=0.002) and hs-CRP(p=0.006) in a Pearson's correlation analysis.Multivariate regression analysis showed that only UA was an independent determinant of FMD(β=-0.237,p=0.036).2.Randomize controlled trial:A total of 108 patients(33/38 from the initial allopurinol group,37/37 from the control group and 38/38 from the normal uric acid group) completed the one-month treatment and follow-up period of observation.No significant differences were observed among the test,the control and the normal uric acid groups in baseline demographic parameters,medications,peritoneal glucose exposure and laboratory parameters except systolic blood pressure,serum uric acid, hs-CRP and flow-mediated dilation.Baseline SBP(p＜0.05),serum uric acid(p＜0.05) and hs-CRP(p＜0.05) was lower and flow-mediated dilation(p＜0.05) was higher in the normal uric acid group.After one month of allopurinol therapy,in the test group, uric acid levels(p＜0.01) and flow-mediated dilation(p＜0.05) improved significantly but not SBP and hs-CRP,whereas in the control and normal uric acid groups no significant changes were recorded(p＞0.05).Baseline FMD was inversely related to UA levels(r=-0.322,p＜0.05).FMD improved significantly in comparison with baseline in the test group(p＜0.05),which was also positively correlated with the degree of allopurinol induced UA level percentage reduction(r=0.463,p＜0.01). Conversely,neither change in FMD nor correlation between this parameter and changes in UA levels of statistical relevance were observed in the control and normal uric acid groups.Conclusion1.In peritoneal dialysis patients,there was independent correlation between UA and FMD.2.In peritoneal dialysis patients,allopurinol can improve FMD significantly and the beneficial effect of allopurinol could have been a direct consequence of the reduced UA levels... |
PDF Full Text Request