Impaired renal function and duration of dialysis therapy are associated with oxidative stress and proatherogenic cytokine levels in patients with end-stage renal disease

OBJECTIVES: The present study was undertaken to clarify the role of the impaired renal function and the dialysis therapy on plasma levels of proatherogenic cytokines and Cu/Zn superoxide dismutase (Cu/Zn SOD)--as a marker of oxidative stress (SOX) in uraemia. DESIGN AND METHODS: We have measured the levels of Cu/Zn SOD, monocyte chemoattractant protein-1 (MCP-1) macrophage inflammatory proteins (MIP-1alpha, MIP-1beta) and vascular endothelial growth factor (VEGF) in the plasma of predialysis (CRF) (n=42), on maintenance hemodialysis (HD) (n=25) or peritoneal dialysis (PD) (n=45) patients and in the healthy volunteers (n=20). RESULTS: The increase in Cu/Zn SOD levels was in PD and HD patients compared to controls (215.56+/-125.18 and 356.28+/-122.57 versus 53.53+/-23.65 ng/ml, respectively). In plasma of the CRF, PD and HD subjects we have also observed the significant increase in the levels of MIP-1beta: [31.5 (2-149), 33.0 (1-203) and 76.0 (9-345), respectively]; MCP-1 (616.50+/-240.15, 943.64+/-348.99 and 968.50+/-355.85, respectively) and VEGF (387.93+/-184.63, 371.56+/-125.18 and 645.56+/-136.30, respectively) compared to healthy people. In the predialysis group, creatinine clearance correlated with Cu/Zn SOD and cytokine levels. Moreover, the cytokine levels were also associated with age. In dialysis patients, the correlations were between duration of dialysis treatment and both Cu/Zn SOD and cytokine levels. There was also a direct relationship between Cu/Zn SOD and both MIP-1beta and VEGF levels. CONCLUSIONS: This study has shown that impaired renal function, age and duration of dialysis treatment are associated with increased oxidative stress and proatherogenic cytokine levels in uremic patients.     

LDL and HDL subclass distribution in patients with end-stage renal diseases

OBJECTIVES: To examine the alterations in LDL and HDL subclass distribution in ESRD patients compared with a control group and to investigate the relationship of LDL particle size to the other plasma lipoproteins levels. DESIGN AND METHODS: Plasma lipids, LDL and HDL subclasses were determined in 63 hemodialysis patients (HD), 42 predialysis patients and 345 control subjects. Lipoprotein subclasses were separated by polyacrylamide 3 to 31% gradient gel electrophoresis. RESULTS: In predialysis group, 88% subjects had small LDL particles compared with 58.5% of hemodialysis patients and 16.5% of control subjects. Mean LDL size particle diameter was significantly smaller in HD and predialysis patients in comparison with controls (p < 0,0005, p < 0,0001; respectively). Significant inverse correlation between LDL particle size and triglyceride level was observed for both patient groups. Decreased levels of the largest HDL2b subclass was found in both predialysis (16.5%) and in HD patients (30%) as compared with controls (50%), and increased levels of the small HDL3a subclass was found only in predialysis group (21%) in comparison with controls (4.5%). CONCLUSIONS: Alterations in LDL and HDL subclass distribution toward smaller particles is the main lipid abnormality associated with atherogensis found in ESRD. ESRD is associated with reduced levels of HDL2b subclass and increased levels of HDL3c subclass, which occurs in coronary artery disease (CAD) as well.     

The effect of different dialysis membranes on oxidative stress and selenium status

BACKGROUND: Oxidative stress is an important risk factor for the development and progression of several complications in hemodialysis patients. The aim of this study was to evaluate the effects of two different dialysis membranes on oxidative stress and selenium status. METHODS: Forty long-term dialysis patients and 20 age-matched healthy controls were enrolled into our study. Serum malondialdehyde (MDA) and selenium (Se) concentrations, and glutathione peroxidase (GSH-Px) activities were determined before and after hemodialysis (HD) using a hemophan (H) or a polysulfone (PS) membrane. RESULTS: MDA levels in the HD patients were significantly higher than those in the control group (p < 0.001). GSH-Px activity and selenium concentrations were significantly lower in HD patients compared to the control group (p < 0.001). MDA levels were significantly increased (p < 0.05); GSH-Px activity and selenium concentrations were significantly reduced (p < 0.001) in the PS membrane group compared to H membrane group after HD. CONCLUSIONS: Comparing with H membrane, PS membrane caused more oxidative stress and lower levels of Se in HD patients.     

Oxidative stress biomarkers and chromogranin A in uremic patients: Effects of dialytic treatment

Objective

To evaluate oxidative stress in uremia and dialysis and chromogranin A, a stress hormone that could be related to oxidative processes.

Methods

Plasma oxidative stress biomarkers (–SH, 8-OHdG, and ox-LDL) and chromogranin A were measured in 89 outpatients (21 uremic patients, 17 in peritoneal dialysis, and 51 in haemodialysis), and in 18 subjects with normal renal function.

Results

–SH groups were significantly reduced in heamodialysis, peritoneal, and uremic patients as compared with the control group (p = 0.01), while 8-OHdG was increased (p < 0.01). No differences were observed for ox-LDL. Chromogranin A was increased in uremic, peritoneal and haemodialysis patients (p < 0.01), showing a positive correlation to 8-OHdG (p < 0.01).

Conclusion

Oxidative stress biomarkers and chromogranin A levels differ between control subjects when compared to both uremic and dialysis patients. No differences were observed between uremic and dialysis patients, suggesting that uremia is the major source of the increase in oxidative stress and CgA levels in patients with end stage renal disease.     

Comparison of oxidative damage in Malaysian end-stage renal disease patients with or without non-insulin-dependent diabetes mellitus

BACKGROUND: Comparisons of oxidative indices and total antioxidant status between end-stage renal disease (ESRD) patients with or without diabetes is scant, especially in the Asian population. METHOD: The assays were carried out according to known established protocols. RESULT: The present study showed that ESRD patients with or without non-insulin-dependent diabetes mellitus (NIDDM) did not have any significant differences in antioxidant enzyme activities, advanced glycated end products (AGE), advanced oxidized protein products (AOPP) and ferric reducing ability of plasma (FRAP), indicating that hyperglycemia does not exacerbate oxidative damage in ESRD. The regulation of catalase and glutathione peroxidase is also altered in ESRD. Elevated FRAP was observed in both ESRD groups (with and without NIDDM). The dialysis process did not alter the antioxidant enzyme activities but decreased AGEs and FRAP and increased AOPP levels. CONCLUSION: Oxidative stress is present in ESRD but this is not significantly exacerbated by hyperglycemia. The contribution of components in the pathology of renal failure towards oxidative stress exceeds that of hyperglycemia.     

Plasma total antioxidant capacity in hemodialyzed patients and its relationships to other biomarkers of oxidative stress and lipid peroxidation.

Patients undergoing long-term hemodialysis (HD) exhibit increased levels of oxidative stress, likely contributing to the increased rate of cardiovascular disease. The present study represents a critical evaluation of some of the most widely used oxidative indicators, as applied to the monitoring of hemodialysis-associated oxidative stress. Total plasma antioxidant capacity was determined by two independent procedures, the total antioxidant status (TAS) and the ferric reducing ability of plasma (FRAP) methods. Plasma lipid peroxidation was assessed by determining the peroxidation products malonaldehyde and 4-hydroxynonenal (MDA-4HNE) as well as lipid hydroperoxides ("Fox-2" and "d-ROMs" methods). Total plasma thiols and plasma alpha-tocopherol were also determined. MDA-4HNE levels were higher in HD patients and decreased following HD, possibly due to passive diffusion across dialysis filters. d-ROMs were also higher in HD patients but exhibited a further increase following the dialysis procedure. Serum alpha-tocopherol did not show any significant differences. Plasma thiols were lower in HD patients and were restored following HD. Plasma total antioxidant capacity determined with either method was unexpectedly higher in HD patients compared to controls, and decreased following HD. These data indicate that, of the biomarkers studied, d-ROMs level is the one more accurately reflecting the oxidative alterations taking place in HD patients, while determination of MDA-4HNE fails to detect oxidation occurring during the HD sessions. In addition, our findings point out that the determination of total antioxidant capacity in HD patients is severely affected by the concomitant fluctuations in plasma urate levels and therefore needs careful interpretation.     

Reliability of oxidative stress biomarkers in hemodialysis patients: a comparative study.

BACKGROUND: Oxidative stress (OS) is considered to play a major role in the development of end-stage renal disease (ESRD) complications. However, conflicting and inconsistent data have been reported on OS in ESRD patients. Our aim was to investigate the reliability of the most popular non-enzymatic plasma OS biomarkers in ESRD. METHODS: Vitamins A (VitA), E and C (VitC), uric acid, plasma antioxidant and ferric-reducing potential (PAP and PRP), thiols (SH), malondialdehyde (MDA) and lipid hydroperoxides (HPO) were determined before and after dialysis in plasma from 33 ESRD patients on hemodialysis, hemodiafiltration or peritoneal dialysis and 20 control subjects. RESULTS: In ESRD patients, high PRP and normal PAP values were positively correlated with VitC levels. After dialysis, PRP levels decreased, while unchanged PAP levels correlated positively with high VitA and transiently recovered SH values. All patients showed high levels of both MDA and cholesterol-normalized HPO. However, while the former significantly decreased after dialysis, the latter were unaffected by treatment. Paradoxical correlations of MDA with both VitA and HPO were found. CONCLUSIONS: Plasma PRP and MDA levels may be dramatically affected by both uremia and dialysis; their use in ESRD patients may therefore lead to OS misevaluation and should be avoided. More reliable results can be obtained using physiologically relevant OS functional tests, such as PAP, and early biomarkers of OS damage, such as SH and HPO.     

尿毒症患者血清氧化蛋白产物水平及不同透析方式的清除效果

目的分析尿毒症患者血清氧化物蛋白产物水平与不同血液透析方式的清除效果。方法将尿毒症患者120例随机分成3组:HD组(单纯的血液透析)、HD+HP组(血液透析+血液灌流)、HD+HDP组(血液透析+血液透析过滤),每组各40例患者,同时以同期健康人、尿毒症没有进行透析者各40例作为参照。对尿毒症患者和健康组的D-二聚体、FIB(纤维蛋白原)、CRP(C反应蛋白)等指标进行检测。同时记录尿毒症患者血液透析前后血清氧化蛋白产物与颈动脉粥样斑块的变化。结果血液透析组与尿毒症没有透析组的D-二聚体、FIB、CRP、氧化蛋白产物指标明显高于健康组(P均0.05),且血液透析组患者的指标高于尿毒症没有透析组(P0.05)。1年后,HD+HP组与HD+HDP组患者血清氧化蛋白产物比HD组更低(P均0.05),且粥样斑块面积更小(P均0.05),颈动脉内膜厚度增加值更少(P均0.05)。结论 HD+HP和HD+HDP模式均能有效清除血清氧化蛋白产物和D-二聚体、FIB、CRP等指标,且HD+HDP模式清除氧化蛋白产物的效果更佳,有利于动脉粥样硬化的延缓。     

The effect of vitamin E supplementation on antioxidant enzyme activities and lipid peroxidation levels in hemodialysis patients

BACKGROUND: This study has been undertaken to investigate the possible alterations of oxidant/antioxidant status in uremic patients undergoing hemodialysis (HD) and the effects of vitamin E supplementation. METHODS: Erythrocyte antioxidant enzyme activities [glutathione peroxidase (GSHPx), superoxide dismutase (SOD) and catalase (CAT)] and thiobarbituric acid reactive substance (TBARS) concentrations as a measure of lipid peroxidation in HD patients have been determined and compared with healthy controls. The patient group consisted of 36 uremic patients 21-75 years of age undergoing maintenance HD three times weekly for an average of 41 months. The efficiency of Vitamin E therapy in dialysis patients was also assessed by re-evaluating antioxidant status of the same patients after supplementation of the vitamin E in a dosage of 600 mg/daily for 14 weeks. RESULTS: A significant decrease in the activities of erythrocyte SOD, CAT and GSHPx and a significant increase in TBARS concentrations were found in patient group compared to control group (p<0.001). A significant correlation between GSHPx activities and duration of HD therapy was also observed (r=-0.46, p<0.01). Vitamin E supplementation caused an increase in GSHPx and SOD activities and a decrease in TBARS concentrations. A slight but not significant increase in CAT activity was also observed by Vitamin E. CONCLUSIONS: The results suggest the presence of an oxidative activity and the possible preventive role of Vitamin E therapy in uremic patients undergoing HD.     

Erythrocyte glutathione peroxidase activity,plasma malondialdehyde and erythrocyte glutathione levels in hemodialysis and CAPD patients

OBJECTIVES: Cardiovascular disease is the major cause of mortality in patients receiving hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) due to chronic renal failure. Increased lipid peroxidation and depletion of antioxidants may contribute to increased risk of atherosclerosis. We have therefore assessed the effect of hemodialysis and CAPD on oxidant and antioxidant status. DESIGN AND METHODS: Plasma malondialdehyde (MDA), Glutathione (GSH) levels and glutathione peroxidase (Gpx) activities were determined in 20 healthy persons (control), 20 patients on HD, 16 patients on CAPD. RESULTS: MDA was elevated in posthemodialysis and CAPD patients in comparison to prehemodialysis and control groups (posthemodialysis 1.39 +/- 0.38 nmol/mL, CAPD 1.26 +/- 0.27 nmol/mL, prehemodilaysis 0.83 +/- 0.22 nmol/mL, controls 0.72 +/- 0.21 nmol/mL p < 0.0001). With respect to antioxidants, glutathione levels were significantly lower in prehemodialysis, posthemodialysis and CAPD groups than those in control group (prehemodialysis 16.82 +/- 6.73 mg/dL RBC, posthemodialysis 31.43 +/- 11.88 mg/dL RBC, CAPD 40 +/- 12.72 mg/dL RBC, controls 62.26 +/- 24.01 mg/dL RBC, p < 0.0001). While erythrocyte GSH levels were significantly lower in the prehemodialysis patients than those in posthemodialysis and CAPD patients (p < 0.0001), it was significantly lower in posthemodialysis patients than those in CAPD patients (p < 0.05). There were no significant differences with respect to erythrocyte Gpx levels among the groups (p > 0.05). CONCLUSIONS: These findings indicate oxidative stress in patients with chronic renal failure which is further exacerbated by hemodialysis and CAPD, as evidenced by increased lipid peroxidation and low antioxidant levels.     

维持性血透患者血浆抗凝血因子的变化及意义

目的 探讨血浆抗凝血因子PC，PC，TM在尿毒症止血、凝血异常导致出血并发症中的作用。方法 采用双抗夹心ELJSA法，发色底物法测定45例尿毒症血透患者血浆PC(PCAg，APC)，PC(TPS，FPS)，TM含量。结果尿毒症患者PCAg,TPS，FPS，TM含量明显高于正常对照组(P＜0．05，P＜0．001)，而PC活性(APC)明显低于对照组(P＜0．001)。维持性血透患者血浆APC，TPS，FPS血透后明显升高(P＜0．05，P＜0．001)；TM血透后明显降低(P＜0．001)。有出血倾向的尿毒症患者血浆APC均明显升高(P＜0．05)。结论 尿毒症患者蛋白C抗凝活性降低(APC)，与尿毒症时高凝倾向和血栓形成有关。血液透析治疗的尿毒症患者在原有高凝状态基础上，透析后仍可激活凝血系统，使体内蛋白C抗凝途径的抗凝活性增强。     

Concentration of Lp(a) and other apolipoproteins in predialysis, hemodialysis, chronic ambulatory peritoneal dialysis and post-transplant patients.

Serum levels of lipids, lipoprotein(a) Lp(a) and other apolipoproteins were determined in 47 predialysis patients, 40 hemodialysis (HD) patients, 39 chronic ambulatory peritoneal dialysis (CAPD) patients, 11 patients after kidney transplantation and 47 healthy subjects as reference group. The predialysis, HD, and CAPD patients had disturbances in the concentration of serum triglyceride (TG), high density lipoprotein (HDL)-cholesterol, apolipoprotein AI (apoAI), total apoCIII, apoCIII present in the particles without apoB (apoCIII non B), and Lp(a) and HDL-cholesterol, low density lipoprotein (LDL)-cholesterol/HDL-cholesterol, HDL-cholesterol/apoAI, apoAI/apoB, and apoAI/apoCIII ratios. Predialysis patients had significantly lower concentrations of HDL-cholesterol and total apoE levels than CAPD patients and total apoE level than HD patients. Moreover, both HD and CAPD patients had significantly increased levels of apoB containing apoE (apoB:E) and apoB containing apoCIII (apoB:CIII). The concentrations of serum TG, total cholesterol, LDL-cholesterol, apoB, Lp(a) in CAPD patients were statistically higher than in HD patients. The patients after transplantation demonstrated normalization of lipid and lipoprotein parameters and lipoprotein ratios except serum levels of TG, total apoCIII, apoCIII non B and the apoAI/apoCIII ratio. We concluded that abnormal lipid and lipoprotein concentrations in patients with uremia may be the cause of their high risk of atherosclerosis, but posttransplant patients exhibited improved levels of serum lipids, Lp(a) and other lipoprotein parameters and lipoprotein composition, which could be an index of decreased atherogenic status.     

不同透析膜对血透患者血清C-反应蛋白及白细胞介素-6水平的影响

目的:探讨不同透析膜对维持性血液透析患者血清C-反应蛋白(CRP)及白细胞介素-6(IL-6)水平的影响。方法:选取尿毒症透析患者54例,分为醋酸纤维素膜(CA130)组、低通量聚砜膜(F6)组及高通量聚砜膜(F60)组,另选取30例尿毒症非透析患者作为非透析组,30例健康体检者作为正常对照组,监测透析前后患者炎症指标水平的变化。结果:透析组患者透析前及非透析组患者CRP、IL-6水平均较正常对照组显著升高(P<0.01)。F6组及F60组透析后CRP、IL-6水平与透析前相比差异均无统计学意义(P>0.05),CA130组透析后CRP、IL-6水平与透析前相比明显升高(P<0.01)。结论:尿毒症患者存在着微炎症状态,这种炎症状态与透析膜的生物相容性有关,而采用高通量透析器透析并不增加这种炎症反应。     

Erythrocyte Na,K pump in uremia. Acute correction of a transport defect by hemodialysis.

We studied the erythrocyte Na,K-pump in chronically hemodialyzed uremic patients, immediately before and after a 4-h period of hemodialysis. Using [3H]ouabain as a probe, the number of Na,K-pump units per erythrocyte did not differ in uremic and control subjects, and hemodialysis had no acute effect on this parameter. In contrast, in these same cells the mean level of Na,K-pump-mediated 86Rb transport was 30% lower in predialysis uremic patients than in controls, and this diminution in the rate of 86Rb transport per pump unit was improved after 4 h of hemodialysis in 17 of 18 subjects. The results of in vitro incubation of normal cells with pre- and post-dialysis sera from uremic patients suggested that a serum factor is responsible for the observed inhibition of Na,K-pump activity. Changes in cell Na concentration during dialysis did not appear to be responsible for the increased rate of Na,K-pump turnover after hemodialysis. However, there was a significant correlation between the extent of rise in pump-mediated 86Rb uptake and the weight loss that occurred during dialysis. We conclude that the ion transport turnover rate of the erythrocyte Na,K-pump is impaired in uremia by a nonouabain like circulating factor. This factor, whose activity is diminished acutely by hemodialysis, may play an important role in the systemic manifestations of the uremic syndrome, and could be an important endogenous regulator of the Na,K-ATPase.     

Paraoxonase-1 concentrations in end-stage renal disease patients increase after hemodialysis: correlation with low molecular AGE adduct clearance

BACKGROUND: Hemorrhagic stroke and ischemic heart disease continue to be key problems in patients with end stage renal failure. Reduced serum paraoxonase (PON-1) activity has been described in these patients, which could contribute to the accelerated development of atherosclerosis. We hypothesized that retention of uremic toxins and or "middle molecules" including advanced glycation (AGE) free adducts and peptides could play a mechanistic role in decreasing PON-1 activity. METHODS: We enrolled 22 ESRD patients undergoing hemodialysis in whom paired pre- and post-dialysis samples were studied along with 30 age-matched control subjects. RESULTS: ESRD patients showed a 76% decrease in PON-1 activity. As expected, ESRD patients had an increase in lipoperoxides and advanced oxidation protein products (AOPP). Our patients had a 3-fold increase in serum AGEs and a striking 10-fold increase in low molecular weight (<10 kDa) AGEs. Post-dialysis samples in all patients displayed an increase in PON-1 activity, which ranged from 4 to 40% of the predialysis value. HDL-cholesterol, apoAI, free cholesterol (as a LCAT surrogate), HDL-subclasses and TG did not change significantly after dialysis. Changes in PON-1 activity display a good correlation (r=0.66, p<0.001) with rates in which creatinine and urea are cleared. Clearance of low molecular weight AGEs after hemodialysis explains 79% of the changes in PON-1 activity and are hence a much better predictor than creatinine changes (r=0.89, p<0.00). In vitro incubation of paraoxonase with serum ultrafiltrates show a time and concentration dependent inhibition of PON-1 by the ultrafiltrates, an inhibition that is up to 3 times higher (from 8 to 24%) when chronic renal failure patients are the source of the ultrafiltrate. CONCLUSION: We showed that HD results in a significant, consistent increase in the activity of the antioxidant enzyme PON-1. The effect, correlates with the effectiveness of dialysis to clear creatinine and urea, and with the clearance of AGE adducts of low molecular weight. This effect was replicated in vitro, showing time and dose dependency. Our results suggest that another cause for the observed lower PON-1 concentrations in CRF are the retention of low-middle molecules and demonstrate a positive effect of hemodialysis in the delicate oxidant-antioxidant state of these patients, that should be weighted against other pro-oxidant effects that have also been shown to occur previously. If the hypothesis that AGEs are the main culprits is proved in further research, this opens a putative therapeutic avenue for AGE blockers in ESRD.     

终末期肾病患者的获得性免疫缺陷和甲状旁腺激素水平的关系

目的 观察维持性血液透析的终末期肾脏病(end-stage renal disease,ESRD)患者的B和T细胞亚群分型,评价T细胞功能与血浆甲状旁腺激素(parathyroid hormone,PTH)之间的相关性.方法 检测接受血液透析和腹膜透析的257例ESRD患者血常规淋巴细胞计数,根据患者是否血液透析和血P...     

Peripheral blood level alterations of MMP-2 and MMP-9 in patients with chronic kidney disease on conservative treatment and on hemodialysis

ObjectivesData concerning the levels of metalloproteinase-2 (MMP-2) and MMP-9 in uremia and dialysis are conflicting and incomplete.Design and methodsWe measured the serum MMP levels in patients with chronic kidney disease (CKD) and undergoing maintenance hemodialysis (HD), and we tried to identify factors that could affect their levels.ResultsMMP-2 and the high sensitivity C-reactive protein (hsCRP) were inversely correlated with hematological parameters in the whole CKD group. CKD patients with stages 3 + 4 showed a significant increase in the MMP-9 levels compared to the other studied groups; this metalloproteinase was inversely correlated with lymphocyte count, and positively correlated with the hsCRP. The MMP-2 levels were higher in pre and post HD patients compared to the control group and CKD stage 1 + 2. In contrast, there was no difference in the MMP-9 levels. Both MMP-2 and MMP-9 were associated with the leukocyte count in pre HD group.ConclusionsThis study suggests a connection between an inflammatory state, biochemical response and the MMP levels in uremic and dialysis patients.     

血液透析对尿毒症患者血清NO-2/NO-3水平的影响

目的　探讨血液透析对尿毒症患者血清NO2 -/NO3 -水平的影响。方法　选择 2 3例尿毒症患者 (血液透析组 12例 ,非血液透析组 11例 ) ,测定血液透析组患者透析前 ,透析 10分钟 ,透析 1小时 ,透析2小时 ,透析后和非血液透析组患者血清NO2 -/NO3 -的水平。结果　血液透析组和非血液透析组尿毒症患者血清NO2 -/NO3 -水平均明显高于正常对照组 ,分别为 (6 7.0± 13.9)umol/l和 (86 .5± 18.2 )umol/l,其中非血液透析组高于血液透析组 (P <0 .0 5 )。血液透析 10分钟时血清NO2 -/NO3 -水平明显高于透析前 ,透析 1小时 ,透析 2小时和透析后。血清NO2 -/NO3 -水平在血液透析前 (6 7.0± 13.9)umol/l与血液透析后 (6 0 .2± 14 .1)umol/l相比无统计学差异。结论　尿毒症患者血清NO2 -/NO3 -水平是升高的 ,血液透析自身可以导致尿毒症患者出现一过性血清NO2 -/NO3 -水平的升高 ,但维持性血液透析可以减少尿毒症患者体内NO的产生。     

Oxidative stress and delta-ALA-D activity in chronic renal failure patients.

In this paper, we studied the influence of uremia and hemodialysis on oxidative parameters and delta-aminolevulinic acid dehydratase (delta-ALA-D) activity in control subjects, patients with chronic renal failure (CRF) on hemodialysis treatment (HD) and in patients not undergoing hemodialysis (ND). An increased lipid peroxidation was observed in the serum of HD and ND patients, as measured by the MDA serum levels. However, the level of MDA from erythrocytes was only elevated in HD patients. Blood catalase activity was increased in HD and ND groups. This study also showed a decreased activity of blood delta-aminolevulinic acid dehydratase (delta-ALA-D) in both groups of patients. This study demonstrated a positive correlation between ALA-D activity and hemoglobin, suggesting that inhibition of this enzyme might enhance anemia in CRF. A negative correlation was found between the alteration in delta-ALA-D activity and oxidative stress, which may indicate that the inhibition of ALA-D can be used as an index of oxidative stress.     

Pituitary adrenal responsiveness to corticotropin-releasing hormone in chronic uremic patients

We investigated the effect of exogenous ovine corticotropin-releasing hormone (oCRH) on plasma levels of adrenocorticotropic hormone (ACTH) and cortisol in 24 chronic renal failure patients: 8 nondialysis (NDCRF), 8 on hemodialysis (HD), and 8 on continuous ambulatory peritoneal dialysis (CAPD). In all groups the acute administration of oCRH caused a further increase (less pronounced in NDCRF patients) in the already elevated levels of cortisol. Following oCRH administration, plasma ACTH rose significantly in CAPD patients, but there was a blunted response of the hormone in the NDCRF and HD groups. The patterns of the ACTH and cortisol response in the last two groups, resemble those observed in chronic stress. We conclude that the hypothalamic-pituitary-adrenal axis in chronic uremic patients, retains the ability to respond to exogenous oCRH. Patients on CAPD, however, display a better, identical to normal response, which can be due to less chronic stress and/or to the more effective clearance of uremic toxins.