Influence of the dialysis membrane on markers of tissue ischemia.

BACKGROUND: Hemodialysis (HD) is often accompanied by adverse effects, such as tissue ischemia. We have already observed an increase in plasma adenosine (ADO) levels during HD sessions, which may be the result of tissue ischemia. Here we evaluate the influence of the dialysis membrane on two sensitive and early markers of ischemia: ADO and ischemia-modified albumin (IMA). METHODS: We included in the study 50 patients with end-stage renal failure, 39 hemodialyzed (mean age 61+/-24 years; 24 male; membranes: 23 synthetic and 16 cellulose based) and 11 undialyzed (mean age 55+/-12 years; 6 male), and 10 healthy subjects (mean age 47+/-11 years; 4 male). We compensated for hemoconcentration during HD by measuring either the IMA to albumin (Alb) or the ADO to Alb ratio. RESULTs: Under basal conditions, the IMA to Alb ratio was not significantly different in patients and controls and HD did not significantly modify this ratio. Conversely, the ADO to Alb ratio (mean+/-SD in micromol/g) was higher in patients before HD compared with either undialyzed patients or controls (before HD: 0.077+/-0.02; undialyzed patients: 0.026+/-0.11; controls: 0.022+/-0.01). During HD, there was a significant increase in the ADO to Alb ratio (before HD: 0.077+/-0.02; after HD: 0.09+/-0.029; p<.01). We found no significant difference in the IMA to Alb or ADO to Alb ratio using either synthetic or cellulose-based membranes. CONCLUSIONS: We concluded that ADO is a more sensitive marker of ischemia than IMA and that, under our HD conditions, the ischemia caused by HD was very weak, independent of the dialysis membrane.     

Pyridoxal 5'-phosphate deficiency in uremic undialyzed, hemodialyzed, and non-uremic kidney transplant patients

In this study, we have investigated plasma pyridoxal 5'-phosphate (PLP) concentrations in undialyzed and dialyzed uremic patients and in kidney transplant subjects, using an enzymatic technique with thermal deproteinization to liberate PLP from plasma proteins. The specificity of the reaction indicates no interference with pyridoxal and only 3% interference with pyridoxamine phosphate. In 17 hemodialyzed patients, a deficiency of about 50% of plasma PLP concentration is found as compared to 25 healthy subjects (22.2 +/- 2.47 vs. 48.8 +/- 3.00 nmol . l-1), as mean +/- SEM). In seven undialyzed uremic patients with end-stage renal failure, the plasma PLP concentration is also decreased (29.3 +/- 1.74 nmol . l-1). The absence of PLP in plasma ultrafiltrates demonstrates that no loss of PLP occurs due to hemodialysis. The daily oral supplementation with 250-750 mg pyridoxal induces a supraphysiological increase in plasma PLP concentration in hemodialyzed as well as in undialyzed patients. In 116 non-uremic kidney transplant subjects, the mean plasma PLP concentration was 33.8 +/- 3.50 nmol . l-1). In 65% of these patients, a marked deficit (below 20 nmol . l-1) was observed. In conclusion, uremic patients have a deficient vitamin B6 state. Its correction with pyridoxal to restore physiological plasma PLP concentration necessitates oral supplementation with lower doses that those widely used at present. In kidney transplant patients a similar plasma PLP deficiency is observed in the absence of chronic renal failure.     

Increase in blood plasma levels of boron and strontium in hemodialyzed patients

Boron and strontium concentrations in blood plasma of controls and hemodialyzed patients from two Centers were determined by inductively coupled plasma emission spectrometry. Boron concentrations in blood plasma were respectively, in controls 2.6 +/- 0.9 mumol/l and in hemodialyzed patients 16.1 +/- 5.6 mumol/l before the dialysis session and 9.5 +/- 3.2 mumol/l at the end. The decrease in blood plasma during the dialysis was concomitant with an increase in the dialysis fluid (1.2 +/- 0.7 mumol/l at the beginning and 4.6 +/- 1.8 mumol/l at the end). Strontium concentrations in blood plasma were respectively, in controls 0.22 +/- 0.06 mumol/l and in hemodialyzed patients 0.62 +/- 0.24 mumol/l before the dialysis session and 0.64 +/- 0.14 mumol/l at the end. The mean concentration of strontium in the dialysis fluid was the same before (0.49 +/- 0.11 mumol/l) and after the dialysis session (0.49 +/- 0.10 mumol/l), but a transfer between plasma and dialysis fluid was shown by individual changes. Some considerations about these results are put forward but their possible clinical consequences are not yet known.     

The changes in NT-proBNP plasma concentrations during dialysis are highly dependent of the dialysis membrane ultrafiltration coefficient

BACKGROUND: NT-proBNP is a powerful marker with diagnostic and pronostic value for heart failure. It is of particular interest in patients with end-stage renal disease who are at high risk for heart failure. The aim of this study was to investigate the effect of hemodialysis on plasma NT-proBNP concentrations. METHODS: NT-proBNP concentration was measured in 67 patients before and after hemodialysis. RESULTS: In the 20 patients dialyzed with a membrane whose ultrafiltration coefficient was below or equal to12, NT-proBNP concentration was comparable after and before dialysis (16611+/-21024 vs. 15216+/-19027 pg/ml, NS). At the opposite, in the 47 patients dialyzed with a membrane whose ultrafiltration coefficient was above or equal to 40, NT proBNP concentration was 35% lower after dialysis compared to before dialysis (11983+/-21819 vs. 18574+/-31862 pg/ml, p<0.0001). CONCLUSIONS: In patients dialyzed with a membrane whose ultrafiltration coefficient is high, dialysis is likely to decrease results by one third. Thus sampling blood before dialysis in hemodialyzed patients appears as the best time to stratify the cardiovascular risk in these patients.     

Lipids and Lipoproteins in Chronic Uraemia. A Study of the Influence of Regular Haemodialysis**

Plasma lipids and lipoproteins were studied in a group of chronic uraemic patients seme of whan were maintained by regular haemodialysis. Compared with healthy individuals, there was a significant increase in plasma triglycerides and in the prebeta-1- and prebeta-2-lipoprotein plasma concentrations. There was no difference between dialyzed and undialyzed patients. Carbohydrate intake was normal, basal plasma insulin and free fatty acid levels were within the normal range. There was no correlation between plasma triglyceride levels and the degree of hypoalbuminaemia, the latter being marked in 30% of the patients. Basal plasma glucagon levels were very high in nearly all dialyzed patients and post-heparin lipoprotein-lipase activity was very low in dialyzed patients. In our experience, regular haemodialysis for 32 weeks did not improve hypertriglyceridaemia.     

Lipids and lipoproteins in chronic uraemia. A study of the influence of regular haemodialysis.

Plasma lipids and lipoproteins were studied in a group of chronic uraemia patients some of whom were maintained by regular haemodialysis. Compared with healthy individuals, there was a significant increase in plasma triglycerides and in the prebeta-1- and prebeta-2-lipoprotein plasma concentrations. There was no difference between dialyzed and undialyzed patients. Carbohydrate intake was normal, basal plasma insulin and free fatty acid levels were within the normal range. There was no correlation between plasma triglyceride levels and the degree of hypoalbuminaemia, the latter being marked in 30% of the patient. Basal plasma glucagon levels were very high in nearly all dialyzed patients and post-heparin lipoprotein-lipase activity was very low in dialyzed patients. In our experience, regular haemodialysis for 32 weeks did not improve hypertriglyceridaemia.     

Cation-exchange chromatography of guanidine derivatives in plasma of patients with chronic renal failure.

Guanidine derivatives are suspected of contributing to the toxic manifestations of uremia. We describe a method for measurement of guanidine derivatives in 5-ml samples of plasma by liquid chromatography. Concentrations of guanidinosuccinate and guanidinobutyrate in plasma were significantly increased both in undialyzed patients with chronic renal failure (5.54 +/- 0.94 and 17.5 +/- 4.07 mg/liter) and those undergoing maintenance hemodialysis (2.35 +/- 0.41 and 19.4 +/- 3.99 mg/liter) when compared to healthy controls (less than 0.4 and 1.0 +/- 0.3 mg/liter, respectively). Creatine and guanidinoacetate concentrations tended to be higher in hemodialysis patients and lower in the undialyzed group of patients with chronic renal failure. This procedure provides a rapid, sensitive, and accurate method for the study of guanidine metabolism in persons with uremia.     

Influence of uremia and hemodialysis on the turnover and metabolic effects of glucagon.

To evaluate the mechanism and role of hyperglucagonemia in the carbohydrate intolerance of uremia, 19 patients with chronic renal failure (12 of whom had undergone chronic hemodialysis for at least 11 mo) and 35 healthy control subjects were studied. Plasma glucagon, glucose, and insulin were measured in the basal state, after glucose ingestion (100 g), after intravenous alanine (0.15 g/kg), and during a 3-h continuous infusion of glucagon (3 ng/kg per min) which in normal subjects, raised plasma glucagon levels into the upper physiological range. Basal concentrations of plasma glucagon, the increment in glucagon after infusion of alanine, and post-glucose glucagon levels were three- to fourfold greater in uremic patients than in controls. The plasma glucagon increments after the infusion of exogenous glucagon were also two- to threefold greater in the uremics. The metabolic clearance rate (MCR) of glucagon in uremics was reduced by 58% as compared to controls. In contrast, the basal systemic delivery rate (BSDR) of glucagon in uremics was not significantly different from controls. Comparison of dialyzed and undialyzed uremics showed no differences with respect to plasma concentrations, MCR, or BSDR of glucagon. However, during the infusion of glucagon, the increments in plasma glucose in undialyzed uremics were three- to fourfold greater than in dialyzed uremics or controls. When the glucagon infusion rate was increased in controls to 6 ng/kg per min to produce increments in plasma glucagon comparable to uremics, the glycemic response remained approximately twofold greater in the undialyzed uremics. The plasma glucose response to glucagon in the uremics showed a direct linear correlation with oral glucose tolerance which was also improved with dialysis. The glucagon infusion resulted in 24% reduction in plasma alanine in uremics but had no effect on alanine levels in controls. It is concluded that (a) hyperglucagonemia in uremia is primarily a result of decreased catabolism rather than hypersecretion of this hormone; (b) sensitivity to the hyperglycemic effect of physiological increments in glucagon is increased in undialyzed uremic patients; and (c) dialysis normalizes the glycemic response to glucagon, possibly accounting thereby for improved glucose tolerance despite persistent hyperglucagonemia. These findings thus provide evidence of decreased hormonal catabolism contributing to a hyperglucagonemic state, and of altered tissue sensitivity contributing to the pathophysiological action of this hormone.     

Comparison of hemostatic disturbances between patients on CAPD and patients on hemodialysis.

OBJECTIVE: Disturbances in hemostasis are common findings in uremic patients. Both bleeding diathesis and thrombosis are observed. The purpose of this study was to assess whether renal replacement therapy in the form of hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) affects coagulation and fibrinolysis in patients with end-stage renal failure. DESIGN: Comparison of hemostatic measures in patients on CAPD, HD, and matched healthy controls. SETTING: Department of Nephrology and Internal Medicine, Bialystok University School of Medicine. PATIENTS AND METHODS: Twenty-four HD patients and 23 CAPD patients were evaluated with respect to platelet aggregation, hemostatic parameters, serum lipids, lipoprotein(a), and cytokines [tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1)]. INTERVENTIONS: Four exchanges of CAPD per day, using 2.0 L dialysate over a period of 25 +/- 31 months; or 4-5 hours of HD 3 times per week for a period of 31 +/- 22 months. RESULTS: Platelet aggregation in whole blood and platelet-rich plasma was significantly impaired in both groups of dialyzed patients compared to healthy volunteers. Markers of endothelial cell injury (thrombomodulin and von Willebrand factor) were significantly higher in HD and CAPD patients compared to the control group. A similar pattern of changes was observed for lipoprotein(a), fibrinogen, tissue factor pathway activity, and factor VII activity. Activity of factor X was significantly enhanced in CAPD compared to HD patients and controls. Euglobulin clot lysis time was significantly prolonged in HD and CAPD patients over controls, being more prolonged in CAPD patients. Markers of ongoing coagulation (thrombin-antithrombin complexes and prothrombin fragments 1+2) were higher in uremic patients, significantly higher in CAPD than in HD. A marker of ongoing fibrinolysis (plasmin-antiplasmin complexes) was higher in uremic patients but was lower in CAPD than in HD patients. Concentrations of TNFalpha and IL-1 were higher in HD than in CAPD patients. CONCLUSION: Patients on CAPD showed evidence of a higher degree of hypercoagulation than HD patients.Thus, hemostatic abnormalities in end-stage renal failure may be affected to some extent by the choice of renal replacement therapy.     

Structural-functional alterations in the heart affecting dynamics of transmitral blood flow during a hemodialysis session

AIM: To study dynamics of transmitral circulation (TMC) during a hemodialysis (HD) session in patients with chronic renal failure (CRF) regarding structural-functional alterations of the heart and baseline condition of the diastolic function of left ventricular (LV) myocardium. MATERIAL AND METHODS: Sixty one patients (34 females and 27 males, mean age 47 +/- 11 years) on programmed HD free of heart valvular disease, ischemic heart disease, acute myocardial infarction, atrial fibrillation. Before and after HD session the patients underwent echocardiography, including Doppler regime. RESULTS: Normal LV geometry was detected in 3 (4.9%) patients, concentric remodeling - in 9 (14.8%), concentric LV hypertrophy (LVH) - in 37 (60.7%), excentric LVH - in 12 (19.7%) patients. The ejection fraction was under 45% in 5 (8.2%) patients. Diastolic dysfunction of LV myocardium was found in 42 (68.9%) patients, TMC characteristic of slow relaxation was registered most frequently (47.6%). A pseudonormal type of TMC was recorded in 16 (38.1%) patients. HD did not change TMC significantly in patients with normal diastolic function (before HD E peak velocity was 88.7 +/- 19.8 cm/s, after - 80.0 +/- 24.6 cm/s, p > 0.05). In patients with initially disturbed relaxation the velocity of early diastolic flow (Vp) (color M-mode Doppler) increased (before HD, Vp was 67.6 +/- 17.1 cm/s, after - 72.9 +/- 15.7 cm/s, p < 0.05), E/Vp reduced (before HDm E/Vp was 1.2 +/- 0.4, after 1.0 +/- 0.4, p < 0.05). The subgroup with initially pseudonormal TMC showed decreased velocity in the E peak (before HD - 103.4 +/- 13.5 cm/s, after - 76.8 +/- 24.0 cm/s, p < 0.001). In restrictive TMC this velocity also decreased - 129.0 +/- 17.8 cm/s and 108.8 +/- 14.7 cm/s, p < 0.05, respectively). CONCLUSION: TMC alteration during a HD session depends more on initial type of diastolic dysfunction than on LV geometry. A HD session improves intracardiac hemodynamics in patients with pseudonormal TMC.     

Plasma adenosine deaminase activity among HIV1 Clade C seropositives: relation to CD4 T cell population and antiretroviral therapy

BACKGROUND: Plasma adenosine deaminase and its isoenzymes(s) activities have been used as diagnostic marker for intracellular parasitism, including HIV infection, and malignancy of immune cells. HIV infection being primarily targeted against CD4 cells, it would be of interest to relate the activity of total plasma ADA and isoenzymes fractions to immune status and antiretroviral therapy. METHODS: In the present study, plasma total ADA activity (ADAT) including ADA1 and ADA2 isoenzyme(s) were assayed among HIV seropositive Clade C (n=90) comprising both asymptomatic (n=71) and symptomatic (n=19) and compared with that of HIV seronegatives (n=35). RESULTS: A significant increase in the activity of ADAT (16.30+/-0.80 v/s 6.18+/-0.30) as well as ADA1 (6.50+/-0.42 v/s 2.34+/-0.16) and ADA2 (9.79+/-0.53 v/s 3.85+/-0.23) isoenzyme(s) among the asymptomatic as well as the symptomatic subjects as compared to respective controls was noted. Increase in plasma ADAT activity, including ADA1 and ADA2 isoenzyme(s), were found to have negative correlation with CD4 counts (r, -0.273; p<0.05). The increased plasma ADAT activity among the asymptomatic HIV seropositive with CD4 counts>500 (13.2+/-1.65; p<0.01) as well as those who were on antiretroviral therapy (19.31+/-1.36; p<0.001) was evident. CONCLUSIONS: These findings suggest that plasma ADA can be a sensitive marker of an ongoing biological insult to host tissues either because of infection and/or side effects of medication. Measurement of plasma ADA activity, along with serological evidence for HIV infection may provide an alternate laboratory tool to monitor intracellular parasitism including secondary infection vis a vis the after effects of therapeutic outcome.     

Effect of hemodialysis on the plasma level of type IV collagenases and their inhibitors

OBJECTIVES: Increased cell expression of matrix metalloproteinase-9 (MMP-9) was associated with the development of atherosclerosis and osseoarticular tissue destruction in hemodialysis patients. In this study, the pre- and post-HD plasma concentrations of type IV collagenases and their inhibitors in HD patients were examined. DESIGN AND METHODS: Commercial ELISA kits and Zymography techniques were used to assay the parameters in 40 patients pre- and post-HD session. RESULTS: After the hemodialysis process, MMP-9, MMP-2 and TIMP-2 levels were 124 +/- 72, 706 +/- 242 and 248 +/- 90 ng/mL, significantly different from the pre-HD values (187 +/- 148, 759 +/- 304 and 43 +/- 14 ng/mL). TIMP-1 were not affected by HD. Female subjects and patients with chronic glomerulonephritis had higher TIMP-2 than their counterparts (p < 0.05). The effect of gender on MMP-2 levels was interacted with that of membrane types (p < 0.01). CONCLUSION: These results indicated that the hemodialysis process tends to decrease the overall activity of the peripheral plasma MMP system in HD patients.     

不同程度慢性肾功能不全患者体内氧化损伤状态的研究

目的 :观察不同程度的慢性肾功能不全 (CRI)患者体内脂质过氧化物和抗氧化酶活性的改变 ,探讨氧化损伤状态和抗氧化系统变化在 CRI发病机制中的作用 ,以及它们与肾功能改变的关系。方法 :采用化学比色法 ,对 36例 CRI患者、12例血液透析患者和 16例正常人的血清丙二醛 (MDA)、谷胱甘肽过氧化物酶(GSH Px)及血清超氧化物歧化酶 (SOD)的含量进行了检测。结果 :36例 CRI患者、12例血液透析患者的血清 MDA水平均明显高于正常对照组〔(4.0 6± 0 .6 7) μmol/ L〕,有显著性差异 (P<0 .0 1) ;GSH Px均明显低于正常对照组〔(12 0 .6 3± 2 7.5 7)× 10 4 U/ L〕,有显著性差异 (P<0 .0 1) ,血清 SOD亦明显高于正常对照组〔(110 .30± 18.6 0 ) k NU / L〕,有显著性差异 (P<0 .0 1)。 36例 CRI患者 SOD、GSH Px和 MDA含量与内生肌酐清除率 (CCr)均呈密切相关 (r G=0 .6 8,P<0 .0 1;r M=0 .5 2 ,P<0 .0 1;r S=0 .4 4 ,P<0 .0 5 )。结论 :自由基、脂质过氧化损伤和抗氧化系统的缺陷在慢性肾功能不全的发病机制中起重要作用 ,并且与肾功能的改变密切相关 ,这些酶活性还可作为临床判断病情严重程度的指标。     

Human plasma and tirilazad mesylate protect stored human erythrocytes against the oxidative damage of gamma-irradiation

Transfusion-associated graft-versus-host disease (TA-GVHD) is a serious condition that under certain circumstances can be lethal in immunosuppressed patients. The risk of TA-GVHD can be reduced in this population by gamma irradiation (gammaRad) of blood components. gammaRad results in production of reactive oxygen species which can damage red blood cells (RBC). Tirilazad mesylate (TM) is a member of the 21-aminosteroids (Lazaroids) family and is a powerful antioxidant. We investigated the ability of TM and human plasma (which contain powerful antioxidants) to protect stored human RBC against the oxidative damage of gammaRad. Fresh intact packed RBC obtained from the normal donors, with and without autologous plasma or TM (0.05 mg mL-1 RBC), were exposed to gammaRad (50 Gy) and stored for 28 days at 4 degrees C. Oxidative damage was assessed by osmotic fragility at 65 mM NaCl concentration (expressed by percentage haemolysis in 65 mM NaCl solution) and lipid peroxidation (measured by thiobarbituric acid reactive substances, TBARS). Our results showed that storage and irradiation of untreated intact RBC increased the osmotic fragility at 65 mM NaCl concentration (65.8 +/- 1.3 vs. 51.20 +/- 0.87% haemolysis; irradiated vs. controls, respectively; P = 0.002) and lipid peroxidation (TBARS = 4.47 +/- 0. 12 vs. 3.45 +/- 0.09 microM L-1 RBC; irradiated vs. controls, respectively; P = 0.001). TM protected the intact RBC against radiation-induced haemolysis (35.8 +/- 5.0 vs. 65.8 +/- 1.3% haemolysis; treated vs. untreated irradiated RBC, respectively; P = 0.02) and lipid peroxidation (TBARS = 2.91 +/- 0.2 vs. 4.47 +/- 0.12 microM L-1 RBC; treated vs. untreated irradiated RBC, respectively; P = 0.005). Addition of autologous plasma to packed RBC significantly reduced the extent of radiation-induced haemolysis by more than six-fold (12.45 +/- 0.26 vs. 65.8 +/- 2.2% haemolysis; irradiated RBC with versus without plasma, respectively; P = 0.0001). In conclusion, these results show that irradiation and storage of blood damages RBC via oxidative processes and addition of autologous plasma and/or TM protects RBC against such damage and possibly enhances their storage and survival.     

Cell-free plasma DNA: a marker for apoptosis during hemodialysis

BACKGROUND: We evaluated whether cell-free plasma DNA might be an appropriate marker for cell damage during hemodialysis (HD) and whether it correlated with annexin V expression and 7-amino-actinomycin D (7AAD) nuclear staining of blood leukocytes. METHODS: Circulating DNA, annexin V, and 7AAD were measured in HD patients before HD, 20 min after start of HD, and after HD had ended. Healthy volunteers provided control measurements. Necrosis and apoptosis were monitored by gel electrophoresis. RESULTS: Plasma DNA concentrations were not significantly different between controls and patients before HD. Circulating DNA increased significantly (P < 0.05) after 20 min of treatment with HD. Post-HD concentrations of DNA were significantly higher compared with pre-HD and controls (P < 0.005). Agarose gel electrophoresis showed ladders typical of apoptosis in post-HD samples. Two subpopulations of CD45+ leukocytes were defined by flow cytometry: annexin V+/7AAD+ population for apoptosis, and annexin V+/7AAD- for early apoptosis. Compared with healthy controls, mean fluorescence (MF) of 7AAD+ apoptotic cells in the annexin V+/7AAD+ subpopulation before HD was not significantly increased. HD increased MF of 7AAD+ cells in the annexin V+/7AAD+ subpopulation. In this subpopulation, MF of annexin V+ cells was significantly higher (P < 0.01). MF of annexin V+ cells in the annexin V+/7AAD+ subpopulation increased during HD. CONCLUSIONS: During HD, cell-free plasma DNA concentrations, annexin V expression, and 7AAD uptake in leukocytes increases. The increase in plasma DNA, appearing as ladders typical of apoptosis, and the 7AAD uptake in leukocytes demonstrate that the predominant portion of circulating DNA in HD patients originates from apoptotic leukocytes.     

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.     

Mechanisms whereby exogenous adenine nucleotides improve rabbit renal proximal function during and after anoxia.

When a suspension of rabbit proximal tubules is subjected to anoxia, ATP falls by 80-90% during 40 min of anoxia, and upon reoxygenation (reox) the cells only recover 25-50% of their initial ATP. Addition of Mg-ATP (magnesium chloride-treated ATP), Mg-ADP, or Mg-AMP (five aliquots of 200 nmol/ml added 10 min apart) during anoxia causes complete recovery of ATP levels, and respiratory and transport function after 40 min of reox. Similar additions of adenosine (ADO), or inosine (INO), or Mg-ATP only during reox are less effective. Lactate dehydrogenase (LDH) release after 40 min of anoxia is 30-40% under control conditions, only 10-15% when adenine nucleotides or ADO are added during anoxia, and 20% when INO is added, suggesting that these additions may stabilize the plasma membrane during anoxia and help preserve cellular integrity. During reox, recovery may depend on the entry of ATP precursors and, therefore, we explored the mechanism whereby exogenous ATP increases the intracellular ATP content. Additions of Mg-ATP, Mg-ADP, or Mg-AMP to continuously oxygenated tubules increase cellular ATP content three- to fourfold in 1 h. The added ATP and ADP are rapidly degraded to AMP, and more slowly to ADO, INO, and hypoxanthine. Furthermore, the ATP-induced increase in cellular ATP is abolished by the exogenous addition of adenosine deaminase, which converts extracellular ADO to INO. These results suggest that the increase in cellular ATP requires extracellular ADO. The ADO obtained from the breakdown of AMP may be preferentially transported into the renal cells to be resynthesized into cellular AMP and ATP.     

Plasma proteinase inhibitor activity and hemostasis tests in children with nephrotic syndrome. Effect of prednisone alone and prednisone plus epsilon-aminocaproic acid treatment regimens: a preliminary report

Neutrophil-derived proteinases cause glomerular injury by proteolysis of the glomerular basement membrane and alterations in glomerular metabolism. Recently, a marked elevation of the plasma elastase complex with alpha1-proteinase inhibitor (alpha 1-PI) both in the acute phase and during remission of nephrotic syndrome (NS) compared with age-matched controls was reported. In experimental immune-mediated glomerulonephritis epsilon-aminocaproic acid (EACA) significantly reduced albuminuria, and it was suggested that this may be linked with the antiproteolytic activity of the drug. We studied plasma antithrombin III (AT-III), alpha 1-PI, alpha 2-antiplasmin (alpha 2-A), alpha 2-macroglobulin (alpha 2-M) activity, and some blood coagulation and fibrinolysis tests in children with frequently relapsing prednisone-responsive NS. Also, the effect of prednisone alone (Group I, n = 9) and prednisone plus EACA (Group II, n = 10) treatment regimens on the studied parameters was estimated. All investigations were performed on admission to the hospital and after approximately 13 days of prednisone alone therapy (Group I), as well as before the administration of prednisone plus EACA and 24 hours after the last dose of EACA, ie, after approximately 5 days of treatment (Group II). Prednisone was administered at the usual dose of approximately 2 mg/kg/d and EACA was given orally at the doses of 72 to 230 mg/kg of body weight per day for 3 to 10 days. In the acute phase of disease, NS patients (n = 19) were shown to have a statistically significant decrease of plasma AT-III (16.4 +/- 4.7 vs. 21.9 +/- 2.5 IU/mL) and alpha 1-PI (1.28 +/- 0.6 vs. 1.97 +/- 0.34 IU/mL) activity, as well as a marked increase in plasma alpha 2-M activity (14.96 +/- 5.81 vs. 9.6 +/- 1.6 IU/mL), and fibrinogen concentration (5.51 +/- 1.78 vs. 2.96 +/- 0.34 g/L) compared to the age-matched controls; no significant changes in plasma alpha 2-A activity, plasminogen concentration, euglobulin clot lysis time, activated partial thromboplastin time (APTT), or thromboplastin time were noted. In children treated with prednisone alone, a marked increase in plasma AT-III (by 76%, P < 0.001) and alpha 2-A (36%, P < 0.019) activity, and a significant decrease of the plasma fibrinogen concentration (6.07 +/- 1.66 vs. 3.17 +/- 1.64 g/L, P < 0.001), and APTT (45.1 +/- 7.6 vs. 33.8 +/- 4.4 s, P < 0.001) were found. Prednisone plus EACA therapy resulted in a significant increase in plasma AT-III activity (by 53%, P < 0.003), whereas plasma fibrinogen concentration and APTT remained unchanged. However, statistically significant differences between the pre- and posttreatment plasma AT-III, alpha 1-PI, and alpha 2-A activities in these patients were observed. There was also a relationship between EACA dose and the percentage change in plasma alpha 2-A activity. In a few patients receiving prednisone plus EACA regimen, side effects that included purulent rhinitis, pharyngitis, increases in body temperature, loose stools, and an approximately 20% to 30% decrease in systolic and diastolic arterial blood pressure were observed. Thus, although the prednisone plus EACA treatment regimen seems to offer new therapeutic possibilities in some patients with NS, it should not be used in acute phase of the disease.     

Antioxidant defense capacity in scleroderma patients

BACKGROUND: Oxidative stress is associated with scleroderma (systemic sclerosis) and is supposed to favor disease progression by complex effects on the vascular endothelium and on fibroblasts. METHODS: Plasma oxidative process marker, thiobarbituric acid-reactive substances, and several markers of antioxidant defense capacity (plasma total antioxidant activity, serum albumin, uric acid and glutathione, superoxide dismutase and catalase) were evaluated by spectrophotometric methods using blood samples collected from 23 scleroderma patients and 21 healthy controls. RESULTS: In scleroderma patients, thiobarbituric acid-reactive substances levels (mmol/L plasma) were significantly elevated (29.3+/-5.8) compared with healthy controls (16.6+/-3.1, p<0.001). Total antioxidant activity (mmol Trolox/L) was significantly lower in scleroderma patients than in controls (1.29+/-0.13 vs. 1.55+/-0.23, p<0.001), as well as the antioxidant gap (mmol Trolox/L) (0.57+/-0.18 vs. 0.92+/-0.22, p<0.001). Superoxide dismutase activity (IU/g hemoglobin) was markedly decreased in patients as compared with controls (395+/-184 vs. 659+/-211, p<0.001). CONCLUSIONS: Lower plasma total antioxidant activity and plasma antioxidant gap in scleroderma patients show that plasma antioxidant defense is deficient in scleroderma patients. As previous studies on this issue are controversial, the decreased erythrocyte superoxide dismutase activity found in the patients in this study needs further investigation.     

血液透析患者超滤量与血压节律和心功能的关系

目的 探讨血液透析患者超滤与血压昼夜节律及心脏结构和功能的关系.方法 维持性血液透析患者42例,对患者加强透析超滤4周,分别检测超滤前后血肌酐、尿素氮、钾、钠及动态血压和心脏彩超.结果 根据24 h动态血压监测发现血液透析患者非杓型血压比例明显升高;超滤前后血压节律和心脏结构有显著性改变(P<0.05),平均每次超滤量与血压和心脏结构变化具有相关性(P<0.05).结论 血液透析患者的夜间高血压与高血容量有关,通过加强超滤可有效控制夜间高血压并改善心功能.