Extracorporeal detoxification for hepatic failure using molecular adsorbent recirculating system: depurative efficiency and clinical results in a long-term follow-up.

Acute liver failure and acute-on-chronic liver failure still show a poor prognosis. The molecular adsorbent recirculating system (MARS) has been extensively used as the most promising detoxifying therapy for patients with these conditions. Sixty-four patients with life-threatening liver failure were selected, and 269 MARS treatments were carried out as a bridge for orthotopic liver transplantation (OLT) or for liver function recovery. All patients were grouped according to the aim of MARS therapy. Group A consisted of 47 patients treated for liver function recovery (median age 59 years, range 23-82). Group B consisted of 11 patients on the waiting list who underwent OLT (median age 47 years, range 32-62). Group C consisted of 6 patients on the waiting list who did not undergo OLT (median age 45.5 years, range 36-54, P = 0.001). MARS depurative efficiency in terms of liver toxins, cytokines, and growth factors was assessed together with the clinical outcome of the patients during a 1-year follow-up. Total bilirubin reduction rate per session (RRs) for each MARS session was 23% (range 17-29); direct bilirubin RRs was 28% (21-35), and indirect bilirubin RRs was 8% (3-21). Ammonia RRs was 34% (12-86). Conjugated cholic acid RRs was 58% (48-61); chenodeoxycholic acid RRs was 34% (18-48). No differences were found between groups. Hepatocyte growth factor (HGF) values on starting MARS were 4.1 ng/mL (1.9-7.9) versus 7.9 ng/mL (3.2-14.1) at MARS end (P < 0.01). Cox regression analysis to determine the risk factors predicting patient outcomes showed that age, male gender, and Sequential Organ Failure Assessment score (but not Model for End-stage Liver Disease score) were factors predicting death, whereas the number of MARS sessions and the ΔHGF proved protective factors. Kaplan-Meier survival analysis was also used; after 12 months, 21.3% of patients in Group A survived, while 90.9% were alive in Group B and 16.7% in Group C (log rank = 0.002). In conclusion, MARS was clinically well tolerated by all patients and significantly reduced hepatic toxins. Better survival rates were linked to an OLT program, but patients' clinical characteristics on starting MARS therapy were the main factors predicting survival. The role of HGF should be evaluated in larger clinical trials.

Effect of a plasma sodium biofeedback system applied to HFR on the intradialytic cardiovascular stability. Results from a randomized controlled study.

BACKGROUND: Intradialytic hypotension (IDH) is still a major clinical problem for haemodialysis (HD) patients. Haemodiafiltration (HDF) has been shown to be able to reduce the incidence of IDH. METHODS: Fifty patients were enrolled in a prospective, randomized, crossover international study focussed on a variant of traditional HDF, haemofiltration with endogenous reinfusion (HFR). After a 1-month run-in period on HFR, the patients were randomized to two treatments of 2 months duration: HFR (Period A) or HFR-Aequilibrium (Period B), followed by a 1-month HFR wash-out period and then switched to the other treatment. HFR-Aequilibrium (HFR-Aeq) is an evolution of the haemofiltration with endogenous reinfusion (HFR) dialysis therapy, with dialysate sodium concentration and ultrafiltration rate profiles elaborated by an automated procedure. The primary end point was the frequency of IDH. RESULTS: Symptomatic hypotension episodes were significantly lower on HFR-Aeq versus HFR (23 ± 3 versus 31 ± 4% of sessions, respectively, P l= l0.03), as was the per cent of clinical interventions (17 ± 3% of sessions with almost one intervention on HFR-Aeq versus 22 ± 2% on HFR, P <0.01). In a post-hoc analysis, the effect of HFR-Aeq was greater on more unstable patients (35 ± 3% of sessions with hypotension on HFR-Aeq versus 71 ± 3% on HFR, P <0.001). No clinical or biochemical signs of Na/water overload were registered during the treatment with HFR-Aeq. CONCLUSIONS: HFR-Aeq, a profiled dialysis supported by the Natrium sensor for the pre-dialysis Na(+) measure, can significantly reduce the burden of IDH. This could have an important impact in every day dialysis practice.

Thrombosis of tunneled-cuffed hemodialysis catheters: treatment with high-dose urokinase lock therapy.

Thrombosis-related malfunction of tunneled-cuffed central venous catheters (TCC) for hemodialysis (HD) currently leads to a high rate of untimely catheter removal. Urokinase (UK) therapy is used for TCC thrombosis/malfunction, but no consensus exists on the adequate dose to obtain thrombolysis. We selected 72 HD patients with TCC and a mean age and HD vintage of 74 years (range 65-87) and 36 months (range 12-61), respectively. All patients received warfarin therapy with a target international normalized ratio (INR) of 1.8-2.5. Coagulative assessment of the patients was obtained by checking the INR, activated partial thromboplastin time, fibrinogen, hemoglobin, and platelets. Sixty-five thrombotic events were recorded during a 3-year follow-up (median 0.3 events/patient/year). The patients selected were randomized into two groups according to a different thrombolytic therapy. Group A comprised 29 thrombotic events in 32 patients who received UK 25,000 IU in both arterial and venous lines of the TCC for each event. UK restored an adequate blood flow rate (BFR) for HD (≥ 250 mL/min) in 4/29 events (13.7%), whereas addition of 50,000 IU to both arterial and venous lines was required in 25/29 events (86.3%). For the same 25 events in the second HD session, a further 75,000 IU of UK was needed for each TCC lumen. Group B comprised 36 thrombotic events in 40 patients who received 100 000 IU of UK in the arterial and venous lumen of the TCC for each event. An adequate BFR was recovered in all events. In 12/36 events (33.3%), 100,000 IU UK for both lumens were needed in the second HD. In conclusion, group B patients obtained (i) a significantly better TCC patency than group A patients; (ii) a low UK administration in the following HD sessions; and (iii) no bleeding complications.

Role of the hemodialysis vascular access type in inflammation status and monocyte activation.

PURPOSE: The aim of this study was to ascertain the role of different vascular access types in inflammatory status, monocyte activation, and senescence in hemodialysis patients. METHODS: We recruited 126 hemodialysis patients, including 51 with arterovenous fistula (AVF), 32 with arterovenous graft (AVG), and 43 with tunneled cuffed catheters (TCC). In dialysis patients enrolled in the study and in a control group of 40 healthy subjects, we measured the serum levels of albumin, CRP, IL-6, and TNF-a, the expression of CD14, CD44, and CD32 on monocyte surface, and the percentage of monocytes exhibiting a senescent phenotype (CD14+CD32+). RESULTS: The patients with AVG compared to those with AVF had: a) higher levels of CRP and TNF-a; b) increased expression of CD14 and CD32 on monocyte surface, with no difference in CD44 expression; c) no difference in the percentage of CD14+CD32+ monocytes. In the comparison of TCC vs. AVF group, we observed significantly higher values of: a) circulating inflammatory markers (CRP, IL-6, TNF-a); b) monocyte surface expression of cellular activation markers (CD14, CD44 and CD32); c) relative count of CD14+CD32+ monocytes. When comparing TCC vs. AVG group, we found: a) no difference in serum levels of CRP, IL-6, and TNF-a; b) no difference in the expression of CD14, CD44, and CD32 on monocyte surface; c) no difference in the percentage of CD14+CD32+ monocytes. CONCLUSIONS: These results suggest that the use of AVG and TCC for dialysis vascular access is associated with serological and cellular indexes of inflammatory reaction, also resulting in a higher degree of monocyte activation and senescence.

Automatic adaptive system dialysis for hemodialysis-associated hypotension and intolerance: a noncontrolled multicenter trial.

BACKGROUND: Hemodialysis is complicated by a high incidence of intradialytic hypotension and disequilibrium symptoms caused by hypovolemia and a decrease in extracellular osmolarity. Automatic adaptive system dialysis (AASD) is a proprietary dialysis system that provides automated elaboration of dialysate and ultrafiltration profiles based on the prescribed decrease in body weight and sodium content. STUDY DESIGN: A noncontrolled (single arm), multicenter, prospective, clinical trial. SETTING & PARTICIPANTS: 55 patients with intradialytic hypotension or disequilibrium syndrome in 15 dialysis units were studied over a 1-month interval using standard treatment (642 sessions) followed by 6 months using AASD (2,376 sessions). INTERVENTION: AASD (bicarbonate dialysis with dialysate sodium concentration and ultrafiltration rate profiles determined by the automated procedure). OUTCOMES: Primary and major secondary outcomes were the frequency of intradialytic hypotension and symptoms (hypotensive events, headache, nausea, vomiting, and cramps), respectively. RESULTS: More stable intradialytic systolic and diastolic blood pressures with lower heart rate were found using AASD compared with standard treatment. Sessions complicated by hypotension decreased from 58.7% ± 7.3% to 0.9% ± 0.6% (P < 0.001). The incidence of other disequilibrium syndrome symptoms was lower in patients receiving AASD. There were no differences in end-session body weight, interdialytic weight gain, or presession natremia between the standard and AASD treatment periods. LIMITATIONS: A noncontrolled (single arm) study, no crossover from AASD to standard treatment. CONCLUSIONS: This study shows the long-term clinical efficacy of AASD for intradialytic hypotension and disequilibrium symptoms in a large number of patients and dialysis sessions.

Long-term effects of high-efficiency on-line haemodiafiltration on uraemic toxicity. A multicentre prospective randomized study.

BACKGROUND: Haemodiafiltration (HDF) may improve survival of chronic dialysis patients. This prospective, multicentre randomized cross-over study evaluated the effects of long-term on-line HDF on the levels of solutes of different molecular weight markers or causative agents of the most common metabolic derangements in uraemia. METHODS: Sixty-nine patients from eight Italian centres were randomly assigned to two 6-month treatment sequences: A-B and B-A [A, low-flux haemodialysis (HD) and B, on-line HDF]. Comparative evaluation of basal levels of small, medium-sized and protein-bound solutes at the end of the two treatment periods and analysis of parameters dependence during the interventions were performed. RESULTS: On-line HDF showed greater efficiency than low-flux HD in removing small solutes (eKt/Vurea 1.60 ± 0.31 versus 1.44 ± 0.26, P < 0.0001) and in reducing basal levels of beta2-microglobulin (22.2 ± 7.8 versus 33.5 ± 11.8 mg/L, P < 0.0001), total homocysteine (15.4 ± 5.0 versus 18.7 ± 8.2 µmol/L, P = 0 .003), phosphate (4.6 ± 1.3 versus 5.0 ± 1.4 mg/dL, P = 0.008) and, remarkably, of intact parathyroid hormone (202 ± 154 versus 228 ± 176 pg/mL, P = 0.03). Moreover, in on-line HDF, lower levels of C-reactive protein (5.5 ± 5.5 versus 6.7 ± 6.1 mg/L, P = 0.03) and triglycerides (148 ± 77 versus 167 ± 87 mg/dL, P = 0.008) and increased HDL cholesterol (49.2 ± 12.7 versus 44.7 ± 12.4 mg/dL, P = <0.0001) were observed. The asymmetric dimethylarginine level was not significantly affected (0.97 ± 0.4 versus 0.84 ± 0.37 µmol/L). Erythropoietin and phosphate binders' doses could be reduced. CONCLUSIONS: On-line high-efficiency HDF resulted in enhanced removal and lower basal levels of small, medium-sized and protein-bound solutes, which are markers or causative agents of uraemic pathologies, mainly inflammation, secondary hyperparathyroidism and dyslipidaemia. This may contribute to reducing uraemic complications and possibly to improving patient survival.

Restless legs syndrome enhances cardiovascular risk and mortality in patients with end-stage kidney disease undergoing long-term haemodialysis treatment.

BACKGROUND: Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by paraesthesia, dysaesthesia and the irresistible urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. Here, we investigated the association between RLS and cardiovascular events risk and laboratory parameters in end-stage kidney disease (ESKD) patients on dialysis. METHODS: One hundred ESKD patients undergoing haemodialysis were enrolled in an 18-month prospective observational study. The main outcomes were the associations of RLS with new cardiovascular events and cardiovascular mortality. RESULTS: RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual diuresis, lower albumin (P = 0.039) and inflammation, but not the dialysis parameters Kt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P = 0.019). New cardiovascular events increased with severity of RLS [intermittent (I-RLS) vs continuous (C-RLS)]. Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P = 0.04). In patients with I-RLS, mortality was 23.8% compared to 55.6% in patients with C-RLS (P = 0.014). Multivariate analysis confirmed the relationship between RLS and mortality. CONCLUSIONS: This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

Effects of unfractioned heparin and low-molecular-weight heparin on osteoprotegerin and RANKL plasma levels in haemodialysis patients.

BACKGROUND: This randomized crossover study investigated the effects of unfractioned heparin (UFH) and low-molecular-weight heparin (LMWH) on intra- and post-dialytic blood levels of osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL) and inflammatory cytokines. METHODS: Forty patients on haemodialysis for at least 12 months were selected. UFH or LMWH was randomly assigned and maintained for 1 month, and then, in the following month, each patient was switched to the other form of heparin. In the mid-week session, we determined the changes in anti-Xa activity, OPG, RANKL, IL-1ß, IL-6 and TNF-α values before heparin administration and after 15 min, 4, 8 and 24 h (T0, T1, T2, T3 and T4 respectively). Since these parameters at the various experimental times showed a non-normal distribution, log transformation was applied in order to run parametric ANOVA, with Bonferroni correction for multiple comparisons. RESULTS: The changes in anti-Xa activity over time were similar but not the same for the UFH and LMWH. A highly significant (P<0.001) increase in anti-Xa activity was detected at T1, regardless of the type of heparin, as confirmed in the comparison of T0 vs T1 using one-way ANOVA. Moreover, with both heparins, significant differences were found in the comparisons of anti-Xa activity at T1 vs T2 (both P<0.001) and at T2 vs T3 (P=0.0003 with UFH; P<0.001 with LMWH). Conversely, the difference in anti-Xa activity at T3 vs T4 was still significant with UFH (P=0.0186) but not significant with LMWH (P=0.728). When comparing anti-Xa activity at T4 vs T0, no significant differences were found either with UFH (P=0.1996) or with LMWH (P=0.7470), thus indicating that 24 h after heparin infusion, anti-Xa activity returned back to the pre-infusion values. When we analysed the changes in OPG levels over time, we found that the administration of heparin, regardless of the type, determined an increase in circulating OPG with a zenith at 15 min (T1), with a return back to the baseline levels within the 24th hour post-infusion. One-way ANOVA revealed significant differences in OPG blood levels at T0 vs T1 with both UFH (P=0.0112) and LMWH (P=0.0288), whereas no significant difference was observed in the comparisons of OPG levels at T1 vs T2, T2 vs T3, T3 vs T4 and T4 vs T0, either with UFH or with LMWH. The circulating levels of RANKL, IL-1ß, IL-6 and TNF-α at the different intra- and post-dialytic times did not show significant variations following heparin administration, either with UFH or with LMWH. One-way ANOVA performed on the log-transformed values of RANKL, IL-1ß, IL-6 and TNF-α at the various experimental times (T0 vs T1, T1 vs T2, T2 vs T2, T3 vs T4 and T4 vs T0) revealed no significant intra- and post-dialytic changes in their blood levels, thus confirming that heparin infusion did not affect their blood levels. CONCLUSIONS: These results suggest that heparin-regulated cyclic increases of OPG might play a role in the vascular pathology of haemodialysis patients.

[Hemodiafiltration reduces mortality and prevents comorbidities? Technical innovations to improve hemodynamics and efficacy]. / L'emodiafiltrazione riduce la mortalita' e previene le comorbidita'? Innovazioni tecniche per migliorare emodinamica ed efficacia.

Hemodiafiltration (HDF) is a dialysis technique characterized by the combination of diffusive and convective depuration. This allows the removal of both low and medium-high molecular weight toxins, keeping the intradialytic hemodynamic status of the patient more stable. Technical innovations in HDF technology aim to enhance the depurative efficacy of the treatment and reduce intradialytic hypotensive events and intolerance. Among these techniques, mixed HDF, middilution HDF and HFR Aequilibrium have particular innovative significance. Mixed HDF and mid-dilution HDF are clinically indicated to enhance the depurative efficacy of HDF and HFR Aequilibrium may serve to widen the depurative range in patients suffering from the malnutrition-inflammation complex syndrome and intradialytic hypotension or intolerance. Mixed HDF and mid-dilution HDF allow to improve the infusion volumes thanks to the intradialytic modulation of the pre/post-infusion ratio (mixed HDF) or the high-volume intradialyzer pre/postinfusion (mid-dilution HDF). HFR Aequilibrium is based on a) separation between convection (first chamber) and diffusion with body weight decrease (second chamber); b) infusion of endogenous ultrafiltrate purified by resin adsorption; c) use of dialysate sodium and ultrafiltration profiles automatically elaborated by a mathematical model incorporated in the software of the dialysis machine.

Risk for contrast nephropathy in patients undergoing coronarography.

Among the causes of in-hospital acute renal failure, contrast-induced nephropathy ranks third in prevalence. Although it represents a condition of renal impairment with spontaneous recovery, contrast nephropathy should always be considered, because it prolongs hospitalization and it may become a severe complication requiring dialysis. The purposes of this study are: (i) to determine if the application of the most effective contrast-induced nephropathy prevention strategies in the Cardiology Intensive Care Unit can prove to be successful in reducing nephropathy risk; and (ii) to identify which of the involved risk factors persist after the preventive treatment. We examined the patients who had a coronarography at the Bentivoglio hospital from April 2007 to April 2008 who required at least 3 days of permanence in hospital due to the presence of potential risk factors; 136 out of 784 patients were included. Among the selected patients, 21 (15.44%) developed a renal impairment compatible with contrast-induced nephropathy. The risk factors that seemed to display the best correlation with risk of contrast nephropathy were advanced age and an ventricular failure (ejection fraction <40%); however, the critical condition did not appear to be due to a single risk factor, but it resulted from the association of more contextual risk factors. Particularly, the concomitant presence of ventricular failure, anemia, diabetes, previous myocardial infarction and advanced age (>70 years) determined a threefold increased risk of contrast nephropathy. Our data suggest that the development of contrast nephropathy following coronarography is associated with worse renal function during hospitalization and at discharge.

Coronary calcifications in end-stage renal disease patients: a new link between osteoprotegerin, diabetes and body mass index?

The aim of the study was to assess the factors potentially involved in coronary artery calcifications (CAC) in end-stage renal disease patients. 253 hemodialysis (HD) patients (92 females, 161 males), aged 62.5 +/- 13.5, who had been on HD treatment for at least 6 months, were enrolled in a cross-sectional study. Calcium-phosphate product (Ca x P), body mass index (BMI), fetuin-A, osteoprotegerin (OPG), osteopontin, transforming growth factor-beta1 (TGF-beta1), fibroblast growth factor-23 (FGF-23) and matrix Gla protein (MGP) were considered. CAC was assessed using multislice spiral computed tomography and calcium score was quantified by means of the Agatston score. The median calcium score was 364 Agatston (range 0-7,336). CAC was detected in 228/253 patients (90.1%). Multivariate regression analysis, adjusted for age and for dialysis vintage, showed that TGF-beta1, OPG and days with Ca x P >55 mg/dl are independent predictors of CAC, while MGP was shown to be a protective factor. Surprisingly, results showed that BMI was a protective factor too: the interpolation with cubic spline function revealed a significant reduction in calcium score in patients with a high BMI (>28). However, when diabetes was considered in the regression analysis, only OPG emerged as a predictor of a high CAC score. The interpolation with spline function continued to show a significant reduction in CAC score in nondiabetic and in diabetic patients with the highest BMI quartile. The protective effect of a high BMI on CAC might represent another example of inverse biology in dialysis patients but it needs to be further addressed in larger longitudinal studies.

5-methyltetrahydrofolate administration is associated with prolonged survival and reduced inflammation in ESRD patients.

BACKGROUND: Hemodialysis (HD) patients have a greatly increased risk of cardiovascular morbidity and mortality. For this reason, attempts are often made to normalize hyperhomocysteinemia. This randomized prospective study sought to determine which risk factors are predictors of mortality and whether high doses of folates or 5-methyltetrahydrofolate (5-MTHF) could improve hyperhomocysteinemia and survival in HD patients. METHODS: 341 patients were divided into two groups: group A was treated with 50 mg i.v. 5-MTHF, and group B was treated with 5 mg/day oral folic acid. Both groups received i.v. vitamin B(6) and B(12). By dividing patients into C-reactive protein (CRP) quartiles, group A had the highest survival for CRP <12 mg/l, whereas no survival difference was found for group B. CRP was the only predictive risk factor for death (RR 1.17, range 1.04-1.30, p = 0.02). Dialysis age, hyperhomocysteinemia, methylenetetrahydrofolate reductase polymorphism, albumin, lipoprotein (a) and folate did not influence mortality risk. Survival in group A was higher than that in group B, namely 36.2 +/- 20.9 vs. 26.1 +/- 22.2 months (p = 0.003). RESULTS: Our results suggest that CRP, but not hyperhomocysteinemia, is the main risk factor for mortality in HD patients receiving vitamin supplements. Intravenous 5-MTHF seems to improve survival in HD patients independent from homocysteine lowering.

Post-coronarography application of continuous veno-venous hemofiltration in the prevention of contrast nephropathy in patients with complex multisystem deficiency.

BACKGROUND: An increased admission of high-risk patients to diagnostic and interventional radiological procedures with contrast medium has resulted in an increase of contrast-induced nephropathy, which now represents the third main cause of hospital-acquired acute renal failure. The pathogenic mechanism of contrast-induced nephropathy (CN) is unclear, but there is much evidence which indicated an interaction between direct tubular cytotoxicity and osmotic/hemodynamic effects. Continuous veno-venous hemofiltration (CVVH) has shown possible benefits in preventing CN. It is not understood when and how prophylactic strategies should be used either in pharmacological therapies or in continous renal replacement therapy (CRRT) approaches. The aim of this study was to evaluate the efficiency of the CVVH technique in preventing CN secondary to emergency radiological procedures in very high-risk patients. PATIENTS AND METHODS: Twelve patients with severe chronic renal impairment (serum creatinine concentration >2 mg/dl with an estimated glomerular filtration rate (eGFR) <40 ml/min) in association with at least two severe comorbidities (such as previous acute myocardial infarction in hypertensive or diabetic patients obesity, cardiac failure with ejection fraction <40%, severe hypotension) were treated with CVVH after coronarography using an iso-osmolar contrast medium (Visipaque, Iodixanol), with or without percutaneous transluminal coronary angioplasty. Adverse events and their association with the interventional radiological procedure were investigated after hemofiltration. RESULTS: Statistically significant differences were observed for both eGFR and serum creatinine at different time points (pre-, post- and 7 days after the procedure) at p<0.05. Statistical analysis of all the variables related to the radiological procedure and the hemofiltration technique did not cause any modification of renal function between the pre- and post-procedure values. No patient showed signs of cardiovascular instability, nor were any episodes of marked hypotension reported during the dialysis session. No patient showed any adverse effects related to the interventional radiological procedure or to the CVVH technique. Renal function, according to serum creatinine concentration and the e-GFR calculation (Cockcroft), did not worsen but had improved when the patients left hospital, with function rates statistically significantly better compared to that on hospital admission, even 7 days after the radiological procedure. CONCLUSION: The present study suggests the efficiency of the CVVH technique in preventing CN in high-risk patients who need to undergo interventional radiological cardiovascular procedures involving the administration of an iodine-based contrast medium.

A modeling study of bilirubin kinetics during Molecular Adsorbent Recirculating System sessions.

This work presents a quantitative description, by means of a mathematical model, of bilirubin removal during Molecular Adsorbent Recirculating System sessions. The model includes four compartments: two for the patient, and two for the albumin circuit. Equations in each compartment express mass preservation, mass exchange between compartments, and bilirubin-albumin binding kinetics. Model development and validation are based on in vivo data of bilirubin concentration acquired in eight sessions at different times during the session. The accuracy of the model in reproducing real data is high (error in blood = -0.3 +/- 0.93 mg/dL), if three parameters, representing the depurative efficacy of the system (the dialysance of the blood filter and the initial and final clearance of the depurative elements in the albumin circuit), are estimated on each single session. However, model accuracy is only slightly deteriorated (error in blood = -0.4 +/- 0.99 mg/dL) if a single set of parameters (fixing the three parameters at their mean values) is adopted. These results suggest that the model may be used a priori (i.e., using a single set of parameters) to achieve a satisfactory prediction of the overall bilirubin removal, as well as a posteriori for the estimation of device parameters. The latter use may allow the investigation of the dependence of these parameters on the operative and clinical conditions, in the effort to arrive at a rationalization and optimization of the treatment.

Standard heparin versus low-molecular-weight heparin. A medium-term comparison in hemodialysis.

BACKGROUND: To compare standard heparin (SH) and low molecular weight heparin (LMWH) in terms of anticoagulation, platelet activation and lipid metabolism, we selected 54 patients who had been on 4-hour hemodialysis three times weekly for at least 12 months, without bleeding disorders or dyslipidemic diseases. 28 were on hemodialysis with Polysulfone low-flux, 26 were on hemodiafiltration with Polysulfone high-flux. All patients underwent EPO. METHODS: During the first 18 months, we administered SH 1,500 IU on starting dialysis and 1,500 +/- 500 IU in continuous intradialytic infusion per session. In the following 18 months, we administered LMWH 64.6 IU/kg on starting dialysis in a single arterious bolus. We assessed aPTT, anti-factor Xa activity, TAT and FPA, beta-TG and PF4. Blood samples were taken monthly at times 0, 30, 60, 180 and 240 min, as well as 1, 4 and 20 h after dialysis end. Predialysis cholesterol, HDL, LDL, triglycerides and lipoprotein(a) were checked monthly. RESULTS: During both LMWH and SH sessions no clotting or major bleeding complications were observed. APTT with LMWH was lower than that found with SH (p < 0.001); aFXa using LMWH was higher than when using SH (p < 0.001); TAT and FPA were lower in LMWH sessions (p < 0.01) than in SH sessions. We also detected lower beta-TG (p < 0.05) and PF4 levels (p < 0.05) using LMWH than using SH. As regards lipids, we only observed a significant decrease in triglycerides after 18 months of LMWH treatment. CONCLUSIONS: Routine use of LMWH during hemodialysis affords a safe and effective alternative to SH, and causes reduced platelet activation.

Low TGF-beta1 serum levels are a risk factor for atherosclerosis disease in ESRD patients.

BACKGROUND: It is thought that transforming growth factor-beta1 (TGF-beta1) might be a key inhibitor of atherogenesis in non-uremic patients. We evaluated the intra- and post-dialytic serum levels of TGF-beta1 in uremic patients to assess if TGF-beta1 is an independent risk factor for cardiovascular diseases, and if any correlation exists between TGF-beta1 and any yet known atherosclerotic risk factors. METHODS: We studied 155 patients who were on regular hemodialysis, with or without clinically significant atherosclerotic vascular disease. Forty-one apparently healthy people were enrolled as a control group. TGF-beta1 was evaluated during the midweek dialysis session, at times 0, 30, and 120 minues, at the end of the session, and 3 hours after the session's end. All hitherto known atherosclerotic risk factors also were evaluated. The investigation was performed over a 24-month follow-up. RESULTS: TGF-beta1 values (mean +/- SD) in dialysis patients were 26.64 +/- 7.0 ng/mL (N=155) compared with 42.31 +/- 6.0 ng/mL in the control group (N=41, P < 0.0001). A weak inverse correlation emerged between TGF-beta1 and age (r=-0.28), TGF-beta1 and lipoprotein(a) [Lp(a); r=-0.35], TGF-beta1 and C-reactive protein (CRP; r=-0.27), and TGF-beta1 and plasminogen activator inhibitor-1 (PAI-1; r=-0.41). TGF-beta1 also correlated with albumin (r=0.31). In the coronary heart disease (CHD) group (N=32) the TGF-beta1 was 26.2 +/- 4.9 ng/mL; in the cerebrovascular disease (CVD) group (N=8) it was 26.7 +/- 3.7 ng/mL and in the peripheral vascular disease (PVD) group (N=9) it was 25.4 +/- 1.7 ng/mL. In dialysis patients with no cardiovascular disease (N=80) TGF-beta1 was 35.1 +/- 6.8 ng/mL (P < 0.0001 vs. CHD, CVD and PVD patients). TGF-beta1 was significantly lower among those patients with triple coronary vessel disease than with the other CHD patients. The Cox analysis demonstrated that a 1 ng/mL reduction in TGF-beta1 concentration was associated with a 9% increase in the relative risk of a cardiovascular event. CONCLUSIONS: TGF-beta1 was significantly reduced in hemodialysis patients, in particular in those with severe cardiovascular disease. Baseline TGF-beta1, diabetes mellitus and serum albumin levels proved to be the only independent contributors to atherosclerotic risk in dialysis patients.

Early, Frequent, and Efficient Hemodialysis: A New Trend or Déjà Vu From the 1970s?

After more than a quarter century of dialysis, two factors are still present in dialysis treatment of chronic renal failure patients: inadequacy of technology (the artificial kidney acts as an artificial glomerulus) and inadequate use of technology in terms of dialysis initiation and frequency. This paper presents the results of two less unphysiological dialysis programs, introduced in Bologna at the beginning of the 1960s, which proved their clinical value and are now becoming trendy, at the end of this century. Features of these programs are twofold: (1) daily dialysis, which aims at making treatment more biologically suited to the patient; its validity relies on lower intra- and interdialytic osmotic fluctuations; (2) early dialysis, which aims at making the patient more biologically suited to the treatment. After more than 25 years it is evident that this treatment has fulfilled its original expectations versus late dialysis. There is a 40% improvement in survival, a 35% decrease in morbidity, and a 24% improvement in the cost/benefit ratio. This report is based on a retrospective analysis of our overall experience and clinical results of chronic hemodialysis carried out in 224 patients on early dialysis and 1210 patients on late dialysis in Bologna from 1967 to 1997. Based on this experience, the following should be regarded as particularly important indications for early dialysis: adequate dialysis facilities; symptomatic patients despite renal creatinine clearances between 15 and 20 mL/min; patients unable to comply with dietary measures; children, to allow for adequate development; patients with diabetes mellitus; candidates for renal transplantation.