Oxidative stress: does it play a role in the genesis of essential hypertension and hypertension of uraemia?

Reactive oxygen species: general aspects Reactive oxygen species, including superoxide radicals, hydrogenperoxide, nitric oxide, peroxynitrite, hydroxyl radicals andhypochlorous acid are by-products of normal metabolic processesin cells. Reactive oxygen species can be found in several cellsincluding macrophages and vascular smooth muscle cells. At lowconcentrations reactive oxygen species can act as physiologicalmediators of cellular responses whereas higher concentrationsmay cause cell damage [1,2]. The major sources of reactive oxygenspecies are leakages from the electron transport chains of mitochondriaand endoplasmic reticulum. Cellular energy metabolism is basedon the production of ATP through the electron transport reactionin which O₂ accepts electrons and H⁺ and then is eventuallyreduced to water. Only 1–2% of the electrons are leakedto generate superoxide radicals in reactions mediated by coenzymeQ and ubiquinone and its complexes. During ageing (and probablyin patients     

Plasma kinetics of 125I-labelled amyloid P component in {beta}2M amyloidosis: A possible approach to quantitate disease activity

Dialysis amyloidosis is one of the most incapacitating complicationsof long-term dialysis treatment. Quantitative assessment ofamyloid deposition using radiolabelled tracers has been recentlyproposed but convincing evidence of its validity in uraemicpatients remains to be provided. We studied the plasma kineticsof i.v. administered ¹²⁵I-labelled serum amyloid P component(¹²⁵I-SAP) in 20 chronic haemodialysis patients compared withthose of nine healthy volunteers and three non-dialysed patientswith systemic amyloidosis. Plasma clearance of the tracer wasabnormal in 17 of 20 dialysis patients in whom plasma radioactivitydeclined in a bi-exponential mode, in contrast to the single-exponentialslope observed in all healthy controls. ¹²⁵I-SAP plasma half-lifeof the second component, probably reflecting metabolic clearance,was significantly prolonged in these dialysis patients comparedwith the healthy controls (35.3 versus 24.6 h, P<0.001).Among the long-term haemodialysis patients the calculated extravasculardistribution of ¹²⁵I-SAP was significantly greater in thosewith severe arthropathy than in asymptomatic patients. Thesefindings demonstrate for the first time that SAP clearance isdisturbed in haemodialysis patients due to both failing renalelimination and retention in extravascular sites. The extravasculardiffusion is greatly enhanced in patients with clinical evidenceof amyloidosis. Therefore the study of plasma ¹²⁵I-SAP kineticspromises to be a valuable tool to quantitate the extent of amyloidosis.     

Relations between vasoactive hormones and diastolic function in hypertensive uraemic patients

Background. Arterial hypertension is a significant risk factor for the high rate of cardiovascular disease in chronic uraemic (CU) patients. Any role that hypertension may play in CU patient outcomes assumes added significance. The elevation of some hormonal factors in early clinical stage could represent a valuable marker of cardiac disease in CU. Aim. This study first investigated the role of several hormones on cardiac diastolic properties in CU patients. Moreover, the study investigated the association of hypertension with both diastolic function and release of vasoactive hormones in CU patients. Results. We have reported that the early impairment of diastolic function is correlated with the elevation of both circulating plasma atrial natriuretic factor and endothelin-1 (ET-1) in hypertensive CU patients. Since the effect of ET-1 on diastolic function is still poorly understood, we have investigated also this issue. In eight additional patients with reduced E/A ratio, but without uraemia, hypertension or chronic heart failure, we have showed a high inverse correlation between the values of E/A ratio and ET-1 plasma concentrations. Conclusions. These results strongly suggest that the elevation in ET-1 levels was correlated with diastolic dysfunction in man. This phenomenon may have important pathophysiological implications suggesting the possibility of an early therapeutic approach in these patients.     

Left ventricular function before and after kidney transplantation. A prospective study in patients with juvenile-onset diabetes mellitus

The aim of the present investigation was to discover whetherdisturbed left ventricular (LV) function limits renal replacementtherapy in patients with juvenile onset diabetes mellitus. Seventeenpatients given functioning kidney grafts were studied non-invasively(M-mode echocardiography, apexcardiography, phonocardiography)before renal transplant and an average of six, 13 and 44 monthsafter transplant. The main pretransplant findings were pronouncedLV hypertrophy with impaired diastolic LV function (prolongedrelaxation time + signs of decreased LV distensibility) anda hyperdynamic circulation. Most of these abnormalities were significantly less severe aftersuccessful kidney transplantation. LV mass decreased by 37%44 months after transplant (p<0.01) and LV diastolic andsystolic volumes decreased with a subsequent increase in ejectionfraction from 0.65 to 0.78 (p<0.01). The LV distensibilityand filling pattern improved significantly while the prolongedrelaxation time was unchanged. These findings imply that pretransplant disturbances in LV functionare related more to factors such as hypertension, volume overloadand uraemia than to diabetes per se because no pronounced improvementin the metabolic disorder resulting from diabetes can be expected,even after the most successful transplant. Disturbed LV functionshould not, therefore, exclude uraemic diabetics from renalreplacement.     

Binding of aprindine and moxaprindine to human serum, α1-acid glycoprotein and serum of healthy and diseased humans

Summary A comparison was made between the binding of the anti-arrhythmic agents aprindine and moxaprindine to human serum, to human serum albumin (HSA), to ₁-acid glycoprotein (₁-AGP) and to a mixture of HSA and ₁-AGP. In serum from healthy volunteers (n=4) the binding of aprindine-HCl 5 µg/ml (13.8 µM) was 93.8% (SD±1.0), and that of moxaprindine-HCl 5 µg/ml (12.8 µM) was 94.1% (SD±1.1). Their binding to the mixture of ₁-AGP and albumin approximated their binding to serum. For ₁-AGP, the binding was similar for both compounds, whereas for HSA the binding of aprindine was more pronounced than that of moxaprindine: for both products the affinity coefficient for binding to ₁-AGP was about 100 times greater than that for binding to albumin. In serum from rheumatoid patients and from patients with renal failure a small but significant increase in binding of aprindine and moxaprindine was observed, approximately 1%. Increased and decreased binding was seen in serum from cirrhotic patients; for example, for aprindine the range in cirrhosis was 96.7%–79.8%, and the range in controls was 95.0%–92.4%. Free drug fraction and ₁-AGP concentration were inversely correlated. The results show that ₁-AGP plays an important role in the binding of aprindine and moxaprindine, and that alteration in the binding of the two compounds in disease states to a large extent can be explained by changes in serum ₁-AGP concentration.     

尿毒症患者甲状旁腺素水平与营养关系的探讨

目的探讨尿毒症患者甲状旁腺素与营养状况的关系,为延缓慢性肾功能不全进展而改善患者营养状况提供临床依据。方法测定患者血清甲状旁腺素(PTH)、ALB、Hb;使用改良定量主观评估表 MQSGA 评估患者营养状况。结果 PTH 与 MQSGA、ALB,存在相关关系(P<0.05),与 Hb 存在显著相关关系( P<0.001);PTH 与 MQSGA、Hb 之间 Logistic 回归分析(P<0.05)。结论 PTH 是影响尿毒症患者营养状况的重要尿毒素。清除血清 PTH 能改善患者营养状况。     

Effects of Three Treatment Modes on Plasma Lipids and Lipoproteins in Uraemic Patients

Plasma lipids, chemical composition of various lipoprotein fractions, apolipoprotein B concentrations and apolipoprotein E phenotypes were studied in 12 uraemic patients on conservative treatment (CT), in 16 patients on haemodialysis (HD) and in 18 patients on continuous ambulatory peritoneal dialysis treatment (CAPD). Plasma total cholesterol and triglyceride concentrations were increased in the CAPD patients in comparison to the HD patients and the control subjects. Moreover, the CAPD patients had higher LDL cholesterol concentration than the CT and HD patients. The HDL cholesterol concentration was lower in the HD and CAPD patients than in the control subjects. The chemical composition of lipoproteins in all fractions of the CT and HD patients and in VLDL, IDL and LDL fractions of the CAPD patients differed from those of the control subjects. The main differences were the increased proportion of triglycerides in VLDL and LDL fractions of all the patient groups and in HDL fraction of the CT and HD patients in comparison to the control subjects. Moreover, the proportion of cholesterol was increased in VLDL and IDL fractions of the CT and the CAPD patients and decreased in HDL fraction of the CT and HD patients compared to the control subjects. In conclusion, in addition to the alterations in the lipoprotein concentrations in uraemic patients there are also marked changes in the chemical composition of the lipoprotein particles that may further contribute to the accelerated atherosclerosis among uraemic patients. The abnormalities are particularly prevalent in CAPD patients.     

Ascorbate-induced hyperoxalaemia has no significant effect on lactate generation or erythrocyte 2,3, diphosphoglycerate in dialysis patients

To examine the possible effects of hyperoxalaemia on anaerobic metabolism and erythrocyte pyruvate kinase activity, we induced a rise in plasma oxalate in 11 dialysis patients by the oral administration of ascorbic acid, 500 mg day-1 for 3 weeks. Blood samples were taken from the same antecubital vein before and after the supplementation period, without venous stasis, after an overnight fast. This protocol allowed patients to be used as their own controls. Five healthy subjects underwent an identical protocol to exclude any effect of ascorbate per se. Mean (SEM) plasma oxalate (mumol l-1) rose from 30.3 (3.5) to 48.4 (6.1) in patients and from 1.4 (0.2) to 6.8 (0.9) in healthy subjects. Whole blood ascorbate (mg l-1) rose from 7.0 (0.7) to 26.6 (2.5) in patients and from 9.3 (1.2) to 17.8 (1.8) in healthy subjects (reference range 7.5-20.0 mg l-1). No changes were observed in either group in plasma creatinine, bicarbonate, haemoglobin, or erythrocyte 2,3,diphosphoglycerate (2,3 DPG) after the 3 week supplementation period. Before supplementation lactate generation (area under curve, mmol min l-1) in the 5 min following a 60 s period of standardized ischaemic forearm exercise was significantly (P = 0.026) greater in patients [69.1 (4.7)] than in healthy subjects [46.9 (6.7)]; no significant change in lactate generation occurred in either group after ascorbate-induced hyperoxalaemia. We conclude that changes in plasma oxalate of the order of 20 mumol l-1 have no significant effect on lactate generation or 2,3,DPG levels in uraemic subjects.     

Erosive Prepyloric Changes in Patients with End-Stage Renal Failure Undergoing Maintenance Dialysis Treatment

We endoscoped 322 of 422 patients with end-stage renal failure undergoing maintenance dialysis treatment to determine the prevalence of erosive prepyloric changes (EPC) in uraemia. EPC grade 1 was found in 79 patients (25%), grade 2 in 16 (5%), and grade 3 in 43 (13%). EPC grades 2 and 3 were commoner among uraemic patients than among non-uraemic patients presenting for gastroduodenoscopy (13 of 198 = 6%; p < 0.001). Patients with EPC grades 2 and 3 were older, had been receiving dialysis longer, and were more likely to be receiving haemodialysis rather than peritoneal dialysis when compared with patients without EPC. Histologic gastritis of the body and antrum was less common among patients with EPC grades 2 and 3 than among patients without EPC. The prevalence of Campylobacter-like organisms was similar in patients with and without EPC.