Altered plasma proteome during an early phase of peritonitis-induced sepsis.

Sepsis is a systemic response to infection commonly found in critically ill patients and is associated with multi-organ failure and high mortality rate. Its pathophysiology and molecular mechanisms are complicated and remain poorly understood. In the present study, we performed a proteomics investigation to characterize early host responses to sepsis as determined by an altered plasma proteome in a porcine model of peritonitis-induced sepsis, which simulated several clinical characteristics of human sepsis syndrome. Haemodynamics, oxygen exchange, inflammatory responses, oxidative and nitrosative stress, and other laboratory parameters were closely monitored. Plasma samples were obtained from seven pigs before and 12 h after the induction of sepsis, and plasma proteins were resolved with two-dimensional gel electrophoresis (n=7 gels/group; before being compared with during sepsis). The resolved proteins were stained with the SYPRO Ruby fluorescence dye and subjected to quantitative and comparative analyses. From approx. 1500 protein spots visualized in each gel, levels of 36 protein spots were significantly altered in the plasma of animals with sepsis (sepsis/basal ratios or degrees of change ranged from 0.07 to 21.24). Q-TOF (quadrupole-time-of-flight) MS and MS/MS (tandem MS) identified 30 protein forms representing 22 unique proteins whose plasma levels were increased, whereas six forms of five unique proteins were significantly decreased during sepsis. The proteomic results could be related to the clinical features of this animal model, as most of these altered proteins have important roles in inflammatory responses and some of them play roles in oxidative and nitrosative stress. In conclusion, these findings may lead to a better understanding of the pathophysiology and molecular mechanisms underlying the sepsis syndrome.

The impact of cytomegalovirus disease and asymptomatic infection on acute renal allograft rejection.

BACKGROUND: Cytomegalovirus (CMV) disease is a risk factor for allograft rejection in renal transplant (RTx) recipients. However, the role of asymptomatic CMV infection remains controversial. OBJECTIVES: To determine the impact of CMV disease and asymptomatic infection on biopsy-proven acute rejection (BPAR) during 12 months post-RTx. STUDY DESIGN: A total of 106 consecutive RTx recipients at risk for CMV (donor and/or recipient CMV seropositive) were followed prospectively for 12 months post-RTx. CMV activity was monitored using nested PCR from whole blood. Three-month prophylaxis with valacyclovir or ganciclovir was given to 94 patients. BPAR episodes were classified according to the Banff 97 criteria. Multivariate Cox proportional hazards model was used to estimate the effect of CMV disease, asymptomatic infection, and other covariates on BPAR. RESULTS: Asymptomatic CMV infection occurred in 23% of the patients and 10% developed CMV disease. The incidence of BPAR was 29%. CMV disease was an independent risk factor for BPAR (HR=3.0, P=0.014), while asymptomatic CMV infection was not (P=0.987). In addition to CMV disease, expanded criteria donor and donor age were independent predictors for BPAR. In univariate analysis, valacyclovir (HR=0.26, P=0.008) decreased the risk of BPAR. A similar trend was observed with ganciclovir (HR=0.42, P=0.058). Only valacyclovir remained significant in multivariate analysis (HR=0.18, P=0.044). CONCLUSIONS: CMV disease, but not asymptomatic infection, is an independent risk factor for BPAR during the first 12 months post-RTx.

Does an alteration of dialyzer design and geometry affect biocompatibility parameters?

The aim of the study was to assess the biocompatibility profile of a newly developed high-flux polysulfone dialyzer type (FX-class dialyzer). The new class of dialyzers incorporates a number of novel design features (including a new membrane) that have been developed specifically in order to enhance the removal of small- and middle-size molecules. The new FX dialyzer series was compared with the classical routinely used high-flux polysulfone F series of dialyzers. In an open prospective, randomized, crossover clinical study, concentrations of the C5a complement component, and leukocyte count in blood and various thrombogenicity parameters were evaluated before, and at 15 and 60 min of hemodialysis at both dialyzer inlet and outlet in 9 long-term hemodialysis patients using the FX60S dialyzers and, after crossover, the classical F60S, while in another 9 patients, the evaluation was made with the dialyzers used in reverse order. The comparison of dialyzers based on evaluation of the group including all procedures with the FX60S and the group including procedures with the F60S did not reveal significant differences in platelet count, activated partial thromboplastin times, plasma heparin levels, platelet factor-4, D-dimer, C5a, and leukocyte count at any point of the collecting period. Both dialyzer types showed a significant increase in the plasma levels of the thrombin-antithrombin III complexes; however, the measured levels were only slightly elevated compared with the upper end of the normal range. Biocompatibility parameters reflecting the behavior of platelets, fibrinolysis, complement activation, and leukopenia do not differ during dialysis with either the FX60S or the F60S despite their large differences in design and geometry features. Although coagulation activation, as evaluated by one of the parameters used, was slightly higher with the FX60S, it was still within the range seen with other highly biocompatible dialyzers and therefore is not indicative of any appreciable activation of the coagulation system. Thus, the incorporation of various performance-enhancing design features into the new FX class of dialyzers does not result in a deterioration of their biocompatibility profile, which is comparable to that of the classical F series of dialyzers.

Valacyclovir for cytomegalovirus prophylaxis reduces the risk of acute renal allograft rejection.

BACKGROUND: Both oral ganciclovir and valacyclovir decrease the incidence of cytomegalovirus (CMV) disease after renal transplantation. Moreover, valacyclovir has been shown to reduce the risk of acute rejection. Our study was designed to compare the efficacy and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease after renal transplantation. METHODS: A total of 83 patients were prospectively randomized to 3-month treatment with oral ganciclovir (3 g/day, n=36, GAN) or oral valacyclovir (8 g/day, n=35, VAL). A control group (DEF, n=12) was managed by deferred therapy. RESULTS: No differences were found in demography, immunosuppression, or donor/recipient CMV serology. The 12-month incidence of CMV disease was 67% in the DEF group compared with 6% in the GAN group and 3% in the VAL group (P<0.001 GAN or VAL vs. DEF; P=0.575 GAN vs. VAL). The biopsy-confirmed acute rejection rate at 12 months was 12% in the VAL group compared with 34% in the GAN group (P=0.030) and 58% in the DEF group (P<0.001). The difference between the GAN and DEF groups was not significant (P=0.087). The average CMV-associated costs per patient were $3,072, $2,906, and $4,906 in the GAN, VAL, and DEF groups, respectively. CONCLUSIONS: Valacyclovir and oral ganciclovir are equally effective in the prevention of CMV disease after renal transplantation. Both regimens are cost-effective. Valacyclovir is associated with a significantly reduced risk of acute rejection compared with both ganciclovir prophylaxis and deferred therapy.

Procalcitonin levels in peritoneal dialysis patients.

OBJECTIVE: To examine whether the levels of procalcitonin (PCT), a new marker of infection and/or inflammation, differ between peritoneal dialysis (PD) patients and healthy volunteers, and whether PCT is detectable in uninfected drained dialysate. DESIGN: Observational cross-sectional study. SETTING: PD unit, department of medicine, in a university hospital. PATIENTS: A total of 28 PD patients, free of systemic infection, and 28 age- and sex-matched healthy volunteers. METHODS: PCT was determined by immunoluminometry; detection range 0.01 - 500 ng/mL, reference range < 0.5 ng/mL. RESULTS: Plasma levels of PCT were significantly higher (Wilcoxon's paired test, p < 0.001) in PD patients (median 0.33 ng/mL) compared with healthy volunteers (0.18 ng/mL). Spearman's test demonstrated a significant positive correlation between PCT and serum C-reactive protein (CRP) (r = 0.59, p < 0.01); correlations between PCT and transferrin, total weekly creatinine clearance (ClCr), and the renal components of ClCr and Kt/V urea were negative. PCT levels in dialysate (PCTd) were 0.07 ng/mL and correlated positively with plasma PCT, serum CRP, and dialysate fibrinogen levels. The dialysate-to-plasma ratio (D/P) of PCT was 0.2. Neither PCTd nor D/P PCT correlated with D/P creatinine at 4-hours of dwell. CONCLUSION: Compared with healthy volunteers, PD patients without overt signs of infection showed increased plasma PCT levels. Given the study design, it is impossible to determine to what extent the increase in plasma PCT is due to reduced elimination and to what extent it reflects the microinflammation of uremia. Based on the D/P PCT gradient, we assume that PCT transport is more likely to occur from the systemic circulation to the peritoneal cavity than vice versa.

The AN69 ST haemodialysis membrane under conditions of two different extracorporeal circuit rinse protocols a comparison of thrombogenicity parameters.

BACKGROUND: Thrombogenicity is an important parameter of haemodialysis (HD) membrane biocompatibility. The surface of the polyacrylonitrile AN69 ST membrane is coated with a polyethylenimine. This modification allows heparin adsorption. The binding of heparin to the membrane surface occurs during priming of the extracorporeal circuit (ECC) by rinsing it with saline and heparin. Our aims were to assess and compare the thrombogenicity of the AN69 ST membrane under conditions of two extracorporeal circuit (ECC) rinse protocols-with and without unfractionated heparin (UFH). METHODS: In a prospective, crossover and randomized study, we examined 10 patients during HD after ECC preparation with either rinse protocols. Prior to HD and at 15, 60 and 240 min, we determined plasma levels of the thrombin-antithrombin complexes (TAT), platelet factor 4 (PF4), heparin concentration (antiXa) and thrombocyte count. Systemic anticoagulation was performed using UFH. RESULTS: During HD after ECC rinse without UFH, there was a significantly earlier and more marked increase in TAT compared with UFH-containing rinse (P <0.05). Using Spearman coefficient, we demonstrated a significant correlation between TAT and antiXa at 60 min (r = -0.534) and 240 min (r = -0.538). A comparison of the TAT/antiXa ratios between rinses at 60 min revealed a significantly higher increase in TAT following UFH-free rinse (P <0.05). There was no difference in PF4 between the rinses. Platelet count did not change significantly during HD using either rinse protocol. CONCLUSION: Based on plasma TAT levels, ECC priming with an UFH-containing solution reduces the thrombogenicity of the AN69 ST membrane. There is no significant difference between both types of priming concerning PF4 and thrombocyte count.

Citrate anticoagulation control by ionized calcium levels does not prevent hemostasis and complement activation during hemodialysis.

The purpose of this study was to determine whether or not regional citrate anticoagulation (RCA) controlled by ionized calcium (iCa(2+)) would overcome thrombogenicity, prevent hemostasis, and complement activation during hemodialysis (HD). RCA was performed in 10 patients during 10 HD sessions using a polysulfone membrane in an effort to keep iCa(2+) at dialyzer outlet at < or =0.4 mmol/L. Compared to baseline, plasma levels of thrombin-antithrombin III complexes rose significantly at 240 min, and tissue factor and complement C5a component levels at 30 and 240 min of the procedure. Thrombocyte count declined significantly at 30 and 240 min, while activated clotting time (ACT) did not increase significantly, and platelet factor 4 as well as von Willebrand factor levels did not alter significantly. While ACT correlated significantly with some thrombogenicity markers, iCa(2+) did not correlate with ACT, changes in hemostasis, or C5a. We conclude the usually recommended iCa(2+) levels in the HD extracorporeal circuit did not guarantee the complete overcoming of thrombogenicity, prevention of hemostasis, and complement activation.

The effect of intravenous iron on oxidative stress in hemodialysis patients at various levels of vitamin C.

BACKGROUND/AIMS: Vitamin C levels decrease during hemodialysis (HD), which deteriorates antioxidant defense. Vitamin C may also act pro-oxidatively, via reduction in Fe(III). We sought to determine whether intravenous iron (Fe(iv))-induced oxidative stress differs in HD patients with low and physiological vitamin C levels and whether intravenous vitamin C (C(iv)) administration during HD would change the response to Fe(iv). PATIENTS AND METHODS: Twenty patients with vitamin C deficiency (median 15.7 micromol/l, range 8.0-22.7) received Fe(iv) (100 mg iron sucrose between 150 and 180 min of HD). After 4 weeks of oral supplementation, the levels of vitamin C were comparable with those of controls (60.1 micromol/l, range 47.4-70.9). Patients were subsequently treated with (1) Fe(iv), (2) Fe(iv) and continuous 2 mg/min C(iv) throughout HD, (3) saline (S), and (4) S+C(iv). Plasma thiobarbituric acid reacting substances (TBARS) and vitamin C were assessed before, during and after FE(iv)(S), and 15, 30 and 60 min after infusion. RESULTS: Fe(iv) induced a comparable rise in TBARS in patients with vitamin C deficiency (before Fe(iv), 1.9 micromol/l, range 1.4-1.9; after Fe(iv), 2.6 micromol/l, range 2.3-2.9; p < 0.01) and in those with normal vitamin C (before Fe(iv), 1.9 micromol/l, range 1.7-2.1; after Fe(iv), 2.6 micromol/l, range 2.5-2.9; p < 0.01). Fe(iv)+C(iv) resulted in a greater increase in TBARS (after Fe(iv), 3.1 micromol/l, range 2.8-3.2) compared with Fe(iv) (p < 0.01). CONCLUSION: Iron sucrose-induced oxidative stress is comparable in HD patients with vitamin C deficiency and in those with normal vitamin C. We documented a pro-oxidative effect of vitamin C during Fe(iv)+C(iv) administration.

Effect of regional citrate anticoagulation on thrombogenicity and biocompatibility during CVVHDF.

This study was designed to assess the principal markers of thrombogenicity and biocompatibility during continuous veno-venous hemodiafiltration (CVVHDF) using regional citrate anticoagulation (RCA). In a prospective study, 11 procedures with a polysulfone membrane were performed in nine critically ill patients with acute renal failure and impaired hemostasis. Blood samples were taken before and during CVVHDF at diafilter outlet--before calcium-induced reversal of the effect of citrate--at 15, 60, 360, and 1440 minutes. In four patients, 10 CVVHDF sessions were performed with systemic heparin anticoagulation (HA) using a polyacrylonitrile membrane. During RCA, blood thrombocyte count, plasma thrombin-antithrombin III complexes, beta-thromboglobulin, and von Willebrand factor levels did not differ significantly from baseline. Plasma D dimer levels rose significantly at 360 minutes; however, the difference between diafilter inlet and outlet levels was nonsignificant. There was a significant increase in plasma C5a concentrations and a decline in blood leukocyte count in the early phase of CVVHDF. Just as in RCA, no increase in plasma thrombogenicity indices was observed during HA. However, clotting times in blood entering patients' circulation were significantly prolonged. Plasma C5a concentrations increased significantly at the beginning of CVVHDF. RCA can effectively inhibit the thrombogenic effect of the extracorporeal circuit in CVVHDF. The effect of HA may be similar, however, at the expense of systemic anticoagulation and risk of bleeding. RCA, performed in a way that overcomes thrombogenicity, does not completely eliminate complement activation and/or transient leukopenia during CVVHDF.

Tissue factor, its inhibitor, and the thrombogenicity of two new synthetic membranes.

BACKGROUND: The aim of the study was to compare the effect of new high-flux hemodialysis membranes made from polyacrylonitrile (AN69ST) and polysulfone (Helixone) on the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) playing a key role in hemostasis. Established thrombogenicity markers were also determined. METHODS: In a clinical prospective randomized study, 10 patients were examined using either membrane at the start and at minutes 15, 60, and 240 of hemodialysis. RESULTS: Increases in the plasma TF levels reached significance at the end of hemodialysis with both membranes, with the Helixone also after 15 min. TFPI levels tended to rise significantly from minute 15 onward while not differing from baseline at the end of the procedure. Judging by the increase in thrombin-antithrombin III complexes, both membranes significantly activated coagulation at the end of hemodialysis. Platelet factor 4 levels, released during thrombocyte and endothelial stimulation, were elevated from the start of procedures. There were no significant differences between the AN69ST and the Helixone in any of the assessed markers. CONCLUSIONS: The AN69ST and Helixone membranes do not differ in their effects on TF and TFPI or even in established thrombogenicity markers.

Prospective comparison of valacyclovir and oral ganciclovir for prevention of cytomegalovirus disease in high-risk renal transplant recipients.

AIMS: To compare the efficacy, costs and safety of oral ganciclovir and valacyclovir in the prophylaxis of cytomegalovirus (CMV) disease in renal transplant (RTx) recipients at high risk of CMV disease. METHODS: A total of 83 patients were prospectively randomized to 3-month treatment with either oral ganciclovir (3 g/day) or oral valacyclovir (8 g/day). A 3rd group received no prophylaxis. Forty-nine patients were considered to be at high risk of CMV disease due to D+R- serologic status, OKT3/ATG treatment and/or acute rejection within 12 months after RTx. Twenty-three high-risk patients were treated with ganciclovir (GAN group), 17 patients with valacyclovir (VAL group), and 9 patients received no prophylaxis (C group). RESULTS: No significant differences were found among the groups in their demographic characteristics, immunosuppressive protocols, D/R CMV serology, or CMV risk factors. The 12-month incidence of CMV disease was 89% in the C group compared with 9% in the GAN group and 6% in the VAL group (p < 0.001, GAN or VAL vs. C; p = 0.713, GAN vs. VAL). Treatment failure (death, graft loss, CMV disease or withdrawal from study) occurred in 17, 6, and 89% in the GAN, VAL, and C groups, respectively (p < 0.001, GAN or VAL vs. C; p = 0.285, GAN vs. VAL). The average CMV-associated costs per patient were EUR 3,161, 3,757, and 7,247 in the GAN, VAL, and C groups, respectively (p = 0.027). CONCLUSION: Valacyclovir and oral ganciclovir are equally effective in the prophylaxis of CMV disease in high-risk RTx patients. Both regimens are cost-effective and help reduce CMV-associated costs by nearly 50% compared with patients without prophylaxis.

Effects of continuous venovenous haemofiltration-induced cooling on global haemodynamics, splanchnic oxygen and energy balance in critically ill patients.

BACKGROUND: A number of haemodialysis studies have demonstrated beneficial effects of cooler dialysates on global haemodynamics in chronic dialysis patients. However, the effects of continuous venovenous haemofiltration (CVVH)-induced cooling on regional perfusion and energy metabolism in critically ill septic patients have not been well defined. METHODS: Nine septic mechanically ventilated patients (age 40-69 years) were investigated during CVVH (ultrafiltration 30-35 ml/kg/h). Baseline data (=WARM 1) were collected when core temperature (Tc) was >37.5 degrees C; the second data set (=COLD) was obtained after 120 min of 'cooling'; and a third set (=WARM 2) was obtained after 120 min of 'rewarming'. During 'warming' (WARM 1 and 2, respectively), both substitution fluids (SFs) and 'returned' blood (RB) were warmed (37 degrees C), whereas during 'cooling', the SFs were at 20 degrees C and RB was not warmed. We measured hepatic venous (HV) haemoglobin oxygen saturation (ShvO(2)), blood gases, lactate and pyruvate. Gastric mucosal PCO(2) (PgmCO(2)) was measured by air tonometry and the gastric mucosal - arterial PCO(2) difference (PCO(2) gap) was calculated. Haemodynamic monitoring was performed with arterial and pulmonary arterial thermodilution catheters. RESULTS: Tcs were significantly altered [WARM 1, 37.9 degrees C (37.6, 38.3); COLD, 36.8 degrees C (36.3, 37.1); WARM 2, 37.5 degrees C (37.0, 38.0); P<0.001; data are median, 25th and 75th percentiles, respectively]. Systemic vascular resistance significantly increased during cooling. As a result, mean arterial pressure increased. Cooling was associated with significant decreases in heart rate, cardiac output, systemic oxygen delivery and consumption. ShvO(2) did not change [WARM 1, 51.0% (44.0, 59.5); COLD, 49.0% (42.0, 58.0); WARM 2, 51.0% (46.0, 57.0); P = NS]. The splanchnic oxygen extraction ratio, the HV lactate to pyruvate ratio, HV acid base status and PCO(2) gap remained unchanged. CONCLUSION: Mild core cooling induced by CVVH may not affect hepatosplanchnic oxygen and energy balance in septic critically ill patients, even though it affects global haemodynamics.

A randomized prospective controlled trial of oral ganciclovir versus oral valacyclovir for prophylaxis of cytomegalovirus disease after renal transplantation.

Oral ganciclovir and valacyclovir reduce the incidence of cytomegalovirus (CMV) disease after renal transplantation (RTx). Our study was designed to compare the efficacy, costs, and safety of oral ganciclovir and valacyclovir in the prophylaxis of CMV disease over the first 6 months after RTx. A total of 38 patients was randomized to 3-month treatment with either oral ganciclovir (1 g t.i.d., n=14, GAN group) or oral valacyclovir (2 g q.i.d., n=12, VAL group). A third group (C, n=12) received no prophylaxis. The patients were monitored by CMV-nested PCR in whole blood. No differences were found between the groups in their demographic characteristics, immunosuppressive protocols, or donor and recipient CMV serology. Thirty-six out of 38 (94.7%) recipients were CMV-seropositive. Over the 6-month post-RTx period, there were 13 episodes of CMV disease in eight (66.7%) patients of the C group compared with none in the GAN and VAL groups ( P=0.0005, GAN vs C; P=0.001, VAL vs C). The incidence of CMV viremia was 30.8%, 50.0%, and 91.7% in the GAN, VAL, and C groups, respectively ( P=0.004, GAN vs C; P=0.07, VAL vs C; P=NS, GAN vs VAL). Treatment failure (death, graft loss, CMV disease, or withdrawal from study) occurred in 14.3%, 0% and 66.7% in the GAN, VAL, and C groups, respectively ( P=0.014, GAN vs C; P=0.001, VAL vs C; P=NS, GAN vs VAL). The average CMV-associated costs per patient (in 2001 euros) were 2,449+/-1,178, 2,485+/-581, and 4,259+/-4,616 in the GAN, VAL, and C groups, respectively. Ganciclovir and valacyclovir were well tolerated, with ganciclovir having had to be withdrawn shortly in one patient only because of thrombocytopenia. In conclusion, oral ganciclovir and valacyclovir are equally safe and effective in the prophylaxis of CMV disease after RTx. Both are cost-effective and help reduce CMV-associated costs by some 40% compared with patients without prophylaxis.

Tissue factor, its pathway inhibitor, and metabolic disturbances in long-term peritoneal dialysis.

BACKGROUND/AIM: The tissue factor (TF) plays a key role in triggering the coagulation system in vivo. Our study was designed to determine whether or not the plasma levels of TF and its pathway inhibitor (TF pathway inhibitor; TFPI) in patients with chronic renal failure (CRF) treated by peritoneal dialysis (PD) (1) are pathologically altered; (2) differ between diabetics and nondiabetics, and (3) depend on the metabolic disorders associated with CRF and/or diabetes. METHODS: Using ELISA, plasma TF and TFPI levels were measured once in 21 PD patients (10 with diabetes, 11 without diabetes) and in 21 healthy subjects. RESULTS: As compared with healthy subjects (TF 282 pg/ml; TFPI 73 ng/ml), both TF and TFPI levels were significantly higher in PD patients with diabetes (485 pg/ml, p < 0.001, and 106 ng/ml, p < 0.01, respectively) and in PD patients without diabetes (480 pg/ml, p < 0,001, and 121 ng/ml, p < 0.001, respectively). The difference between diabetics and nondiabetics was not significant. In stepwise regression analysis, the TF levels depended on serum creatinine (partial correlation 0.39, p < 0.05), glycemia (0.43, p < 0.01), and insulin (-0.43, p < 0.05), and the TFPI levels depended on creatinine (partial correlation 0.67, p < 0.001), apolipoprotein B (0.46, p < 0.01), and plasma fibrinogen (0.43, p < 0.01). CONCLUSIONS: CRF patients on PD show increased plasma TF and TFPI levels. There is no difference between diabetics and nondiabetics. The TF and TFPI levels depend significantly on the renal function, as assessed by serum creatinine, and on some metabolic disorders. Elevated TF and TFPI levels may be related to thrombosis and atherosclerosis in CRF patients on PD.

Does treatment modality have an impact on anemia in patients with chronic renal failure? Effect of low- and high-flux biocompatible dialysis.

Renal anemia significantly affects the morbidity and mortality of dialysis patients. The aim of the present study was to establish whether the severity of anemia and success of its treatment differs when using high-flux (HF) or low-flux (LF) hemodialysis. Twenty-five patients on long-term hemodialysis with a mean hematocrit (Hct) of 33%, S alb of 36 g/L, and Kt/V urea of 1.5 were divided into Groups X (n = 13) and Y (n = 12) in a prospective randomized crossover study. Group X was initially treated with LF hemodialysis to be followed by HF hemodialysis for 8 weeks each time. Group Y started with 8 week HF hemodialysis and continued, after crossover, with 8 weeks of LF hemodialysis. HF and LF hemodialysis were performed with polysulfone dialyzers F 7HPS and F60S (Fresenius Medical Care, Bad Homburg, Germany). Hct values, examined at 2 week intervals, did not differ significantly between Groups X and Y during 16 weeks of the study at any measuring interval. In another analysis, all results of HF hemodialysis (first 8 weeks of Y + second 8 weeks of X) were pooled as were all data of LF hemodialysis (first 8 weeks of X + second 8 weeks of Y). No significant relationships were noted between duration of treatment with HF hemodialysis and Hct (n = 72, rS = 0.11, p = 0.36) and between duration of LF hemodialysis and Hct (n = 74, rS = 0.02, p = 0.87) in the newly formed groups. The Hct measured during HF hemodialysis and LF hemodialysis did not differ significantly. Analysis of variance did not reveal a relationship between Hct and the HF or LF membrane. As HF and LF hemodialysis differed significantly in Kt/V urea, the variables were adjusted to identical Kt/V urea using analysis of covariance. No relationship between Hct and dialysis membrane permeability was demonstrated even in this case. Use of biocompatible LF and HF membranes in standard hemodialysis modes under conditions of adequate dose of dialysis and the time period studied did not result in different effects on anemia.

Fibrinolysis defect in long-term hemodialysis patients with type 2 diabetes mellitus and its relation to metabolic disorders.

BACKGROUND/AIMS: Patients with chronic renal failure (CRF) secondary to diabetes mellitus show a high incidence of atherosclerosis with its thrombotic complications. Both CRF and type 2 diabetes mellitus (DM2) results in fibrinolysis defects causally related to atherogenesis and thrombogenesis. It is not well known whether or not and, if so, how fibrinolysis is altered in patients with both CRF and DM2. Our study was designed (1) to identify the fibrinolysis defect present in patients with DM2-mediated CRF and treated by long-term hemodialysis (DM2HD), and (2) to establish whether the fibrinolysis defect is related to the metabolic abnormalities observed in CRF or DM2. METHODS: Sixteen DM2HD patients and 23 healthy individuals (HI) had their euglobulin clot lysis time (ECLT), and tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) activities (act) and concentrations (ag) assessed before and after standard fibrinolytic stimulus (i.v. administration of 0.4 microg/kg BW 1-deamino-8-D-arginine vasopressin, DDAVP) along with metabolic status markers. RESULTS: DDAVP caused a significant shortening of ECLT, rises in tPA act and ag, and a significant decrease in PAI-1 act. PAI-1 ag declined significantly in HI, but not in DM2HD. A comparison of responses to DDAVP revealed the groups differed significantly in the change in PAI-1 ag. Whereas, in HI, PAI-1 ag decreased by 11.8 ng/ml, no decrease was seen in DM2HD (0.0 ng/ml) (p < 0.0001; medians given; unpaired Wilcoxon's test). Stepwise regression analysis showed the change in PAI-1 ag was highly group-specific (DM2HD vs. HI, regression coefficient 21.22; partial correlation 0.58; p < 0.0001) and, also dependent on the serum concentrations of apolipoprotein A-I (-32.41; -0.46; p < 0.01) and homocysteine (0.35; 0.36; p < 0.05). CONCLUSIONS: Patients with type 2 DM and CRF on long-term hemodialysis have a fibrinolysis defect manifesting itself after standard fibrinolytic stimulus by an insufficient decrease in PAI-1 concentrations. The defect is related to decreased serum levels of apolipoprotein A-I and increased serum levels of homocysteine. The defect might be a factor contributing to accelerated atherosclerosis and thrombotic complications in these patients.