Cardiovascular outcome in asymptomatic hemodialysis patients submitted to aggressive medical therapy: results of a four-year follow-up.

AIM: Cardiovascular disease is a leading cause of morbidity and mortality in end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Neither traditional nor emerging risk factors for cardiovascular disease can explain completely this excess of morbidity and mortality and the role and timing of primary prevention strategies in this population has not been clarified. The aim of this study was to assess if an aggressive pharmacological preventive treatment may reduce the myocardial ischemic burden and then improve the cardiovascular outcome In ESRD patients. METHODS: Forty-three asymptomatic ESRD patients on maintenance HD were evaluated. Asymptomatic patients with neither history nor clinical evidence of cardiovascular disease were considered. A total of 31 ESRD patients were enrolled into the study and were submitted to Tc-99m SESTAMIBI myocardial gated- single-photon emission computed tomography (SPECT) stress test. All patients then received an aggressive medical regimen with statins, antiplatelet drugs, ACE inhibitors (ACE-I) and/or Angiotensin II Receptor Blockers (ARB) and other hypotensive, glucose-lowering medications, sevelamer, calcium carbonate and calcitriol if required. RESULTS: A significant reduction of coronary functional reserve was found in more than 50% of otherwise asymptomatic HD patients and may often be reverted by prolonged aggressive medical therapy. After a four-year follow-up under aggressive medical therapy no significant difference was observed neither in the incidence of conventional and emerging cardiovascular risk factors nor in cardiovascular outcome of patients with or without silent myocardial ischemia (SMI). CONCLUSION: As cardiovascular disease (CVD) is by far the first cause of death in ESRD, an aggressive medical management may be highly advisable for the primary prevention of major adverse cardiac events in all HD patients despite the stress test evidence of inducible myocardial ischemia .

The usefulness of the prognostic inflammatory and nutritional index (PINI) in a haemodialysis population.

BACKGROUND AND AIM: Protein-Energy Wasting and inflammation are the principal risk factors of haemodialysis complications. We evaluated the reliability of a simple and non expensive test, the Prognostic Inflammatory and Nutritional Index (PINI), for regular screening of maintenance haemodialysis (MHD) patients in order to detect early onset of inflammation and malnutrition. METHODS AND RESULTS: 121 adult patients on maintenance dialysis were followed up for 32 months and screened every 6 months for PINI, calculated as alpha1-Acid Glycoprotein (alpha1-AG)xC-Reactive Protein (CRP)/AlbuminxTransthyretin. PINI score < or =1 was considered normal. Patients were stratified according to their PINI score: 86 patients (71.66%) had a normal score, whereas 35 (28.33%) had PINI > or = 1. The latter also had higher CRP levels, despite no clinical evidence of inflammation at the time of enrolment. Survival in patients with normal PINI was similar to patients with normal CRP, while in patients with abnormal PINI it was significantly lower than in patients with low serum albumin (p<0.05) or elevated CRP (p<0.05). After follow-up, all surviving MHD patients with PINI > or = 1 had at least one cardiovascular event vs 2.5% of patients with PINI > or = 1. CONCLUSION: The assessment of PINI can reliably identify MHD patients at higher risk of mortality and morbidity even in the absence of overt Malnutrition-Inflammation Complex Syndrome (MICS). This simple test appears to be more sensitive and specific of the single components, and not expensive, so that it could be routinely used to identify patients with sub-clinical inflammation and/or malnutrition.

Treatment of hyperhomocysteinaemia in haemodialysis patients at high cardiovascular risk.

OBJECTIVES: Cardiovascular disease (CVD) is the main cause of death among haemodialysis (HD) patients. Emerging cardiovascular risk factors such as oxidative stress and chronic inflammation are involved in these patients together with traditional risk factors. Here we investigate the effects of a short-term folate treatment on some markers of chronic inflammation in two groups of HD patients with and without vascular occlusive disease (VOD). PATIENTS AND METHODS: Homocysteine (HCy), C-reactive protein (CRP), Folate, fibrinogen and alpha1 acid glycoprotein (alpha1AGP) were dosed before and after a 3-month course of high-dose folate (25 mg intravenous calcium laevofolinate pentahydride once weekly) and again after a one-month washout in 15 HD patients with established VOD (group A) and in 15 comparable HD patients with no diagnosis of VOD (group B). RESULTS: Baseline HCy and CRP were significantly elevated in patients of both groups A and B compared to normal values. Folate treatment significantly reduced HCy in patients of both groups A and B and alpha1AGP only in patients of group A, while the other markers were not modified. After the one-month washout a significant raise of CRP could be observed in patients of group A; again, the other markers were not modified. CONCLUSIONS: Our results suggest that significant reduction of serum HCy can be achieved in both patients with or without VOD after administration of high-dose folic acid. Hence, folic acid supply is useful in the treatment of hyperhomocysteinemia in HD patients, although it is not sufficient to modify their chronic inflammatory status.

Cardiac calcifications in hemodialysis patients assessed with spiral computed tomography.

AIM: Cardiac disease is a major cause of mortality in uremic patients. The aim of this paper was to evaluate cardiac calcium content in uremic patients with multislice computed tomography (MSCT). METHODS: The study has been carried out on 120 uremic and 28 nonuremic patients affected by cardiovascular disease. Serum calcium, phosphorus, calcium-phosphate product, intact PTH were assayed. Several lipidic and nutritional parameters were measured. Calcification values obtained with the MSCT were reported in terms of Agatson scores. RESULTS: We found that the average score values in cohort on uremic was 10 times higher than in nonuremic patients (score values 3.389 vs 328). Cardiac calcification score was found to be correlated significantly to age (P=0.006), HD age (P=0.010), serum calcium (P=0.006), iPTH (P=0.004). Multiregression analysis (MRA) with the cardiac score as dependent variable selected the following variables (R(2) 0.612): age (P=0.002), HD age (P=0.010), serum cholesterol (P<0.000), triglycerides (P=0.001) and inversely HDL cholesterol (P=0.001) and non-HDL cholesterol (P=0.001) as predictive variables for cardiac score. By comparing patients with scores lower and higher than 400, the group with score <400 showed a significantly lower age (P=0.0001), HD vintage (P=0.01) and a significantly higher serum cholesterol (P=0.009), HDL cholesterol (P=0.05) and non-HDL cholesterol (P=0.05). CONCLUSIONS: The MSCT could help in identifying and stratifying high-risk patients to implement preventive strategies. The control of mineral metabolism and of lipid levels is important in prevention of arterial calcification in uremic patients.

N-3 PUFAs reduce oxidative stress in ESRD patients on maintenance HD by inhibiting 5-lipoxygenase activity.

Reactive oxygen species formation and release of pro-inflammatory/pro-atherogenic cytokines, that is, interleukin 1-beta and tumor necrosis factor-alpha, need the activation of the arachidonic acid cascade via the enzyme 5-lipoxygenase (5-Lox). 5-Lox activity and expression are significantly increased in peripheral blood mononuclear cells (PBMCs) of end-stage renal disease (ESRD) patients on maintenance hemodialysis (HD). Diets enriched with n-3 polyunsaturated fatty acids (PUFAs) (omega-3) have been associated to a lower incidence of coronary heart disease (CHD) and a reduction in atherosclerotic lesions. Omega-3 may interfere with the arachidonic acid cascade by inhibiting 5-Lox. Lipid peroxidation, leukotriene B(4) (LTB(4)) production, 5-Lox activity and expression were investigated in PBMC isolated from ESRD patients under maintenance HD before and after a 3-month oral supplementation with omega-3 at a daily dose of 2700 mg of n-3 PUFAs at the average eicosapentaenoic acid/docosaesaenoic acid ratio of 1.2 and finally after a further 3-month washout with no omega-3 supplementation. PBMCs from non-uremic volunteers were also investigated for comparison to normal parameters. Administration of omega-3 reduced significantly lipid peroxidation (P < 0.0001), LTB(4) synthesis (P < 0.0001) and 5-Lox activity (P < 0.0001), with no effect on 5-Lox protein expression. After the 3-month washout, all parameters were comparable to those observed before treatment. Our results resemble those obtained after oral administration of vitamin E and are consistent with a reversible, dose-dependent inhibition of 5-Lox by omega-3. Upregulation of 5-Lox may also be related to the increased mitochondrial damage and apoptosis of PBMCs observed in ESRD patients compared to non-uremic controls. Omega-3 may thus protect PBMCs of ESRD patients against oxidative stress.

Vitamin E suppresses 5-lipoxygenase-mediated oxidative stress in peripheral blood mononuclear cells of hemodialysis patients regardless of administration route.

A number of pathological conditions caused by oxidative stress have been reported in uremic patients undergoing maintenance hemodialysis (HD). Enhanced lipid peroxidation was previously observed in peripheral blood mononuclear cells (PBMCs) of HD patients. Upregulation of 5-lipoxygenase (5-Lox) activity and protein content with enhanced production of leukotriene B(4) (LTB(4)) and membrane lipoperoxides was also shown in PBMCs of HD patients. Administration of free vitamin E specifically inhibited 5-Lox activity without affecting gene expression at the protein level. To assess whether oral or intramuscular (IM) administration of vitamin E may suppress 5-Lox in HD patients, PBMCs from 16 subjects on maintenance HD therapy for at least 6 months were investigated before and after a short course of IM or oral administration of vitamin E (8 patients per group). PBMCs from 13 healthy controls were also evaluated and assumed as the reference standard. Vitamin E significantly reduced lipid peroxidation, LTB(4) content, and 5-Lox activity in PBMCs, whereas 5-Lox gene expression at the protein level was not affected. There were no significant differences in these parameters between patients treated with IM or oral vitamin E. PBMCs of HD patients showed enhanced membrane lipid peroxidation and release of LTB(4), both linked to upregulation of 5-LOX: 5-Lox activity and related oxidative stress were significantly (although not completely) suppressed by vitamin E regardless of the administration route.

Efficacy of epidural anesthesia for retroperitoneoscopic renal biopsy.

Laparoscopic procedures are performed using general anesthesia due to the perceived limitations of regional anesthesia in the upper abdomen and retroperitoneum. We present our initial experience with epidural anesthesia for retroperitoneal laparoscopic renal biopsy.

Activation of 5-lipoxygenase and related cell membrane lipoperoxidation in hemodialysis patients.

Lipid peroxidation was shown at the membrane level in peripheral blood cells of patients hemodialyzed on cuprophan dialyzers, and was mainly attributable to the generation of conjugated hydroperoxides in the lipid bilayer. The oxidative index (i.e., the A234/205 ratio) of membrane lipids was 3.2-fold higher in hemodialysis patients than in healthy control subjects, and also the level of leukotriene B4 was significantly increased (up to 1.7-fold over control). Both membrane peroxidation and release of leukotriene B4 were linked to upregulation of 5-lipoxygenase activity (up to 2.4-fold over control) and expression at the protein level (up to 1.9-fold). Vitamin E, the most important lipophilic antioxidant, prevented both membrane peroxidation and release of leukotriene B4 by inhibiting 5-lipoxygenase activity without affecting enzyme expression. Similar results were observed in patients hemodialyzed on polymethylmetacrylate membranes, but in this case the activation of 5-lipoxygenase was less pronounced. The use of a purified 5-lipoxygenase demonstrated that vitamin E was a reversible inhibitor of enzyme activity (IC50 = 35 +/- 4 microM), further characterized as noncompetitive (Ki = 30 +/- 3 microM). Taken together, the results reported here shed some light on the mechanism responsible for the oxidative damage in hemodialysis. Moreover, the beneficial effect of vitamin E described here may have relevance for the therapy of patients with kidney disease.

Cardiac function and oxygen balance in septic patients during continuous hemofiltration.

The aim of this work was to study hemodynamic, oximetric and metabolic parameters in septic patients during continuous hemofiltration, in order to determine whether the changes in hemodynamic parameters can influence the oxygen utilization in peripheral tissues. 29 multiple organ failure patients with septic shock were studied during the first 48 h of continuous hemofiltration: 18 were submitted to CAVH and 11 patients were treated with CAVHD to correct ARF and fluid overload. Our data show that RVEF improves and REDVI reduces progressively during treatment, together with a significant reduction of the cardiac index after 48 h of CAVH(D). There were no significant variations in oxygen tissue parameters, while plasma lactate was reduced significantly. In conclusion, our data confirm that continuous hemofiltration may be useful in septic patients to correct fluid overload and ARF, without affecting hemodynamic stability and oxygen balance. Moreover, in septic patients, this technique improves hemodynamics, reduces the filling pressure in the right heart and reduces hyperdynamic response as CI and SVRI, without any negative effects on O2 balance.

Blood purification procedures for acute renal failure: convenient strategy related to clinical conditions.

The choice in the renal replacement therapy of acute renal failure (ARF) should match the patients' individual needs and the characteristics of available therapies. 141 ARF patients, 65 with "isolated' ARF (group I) and 76 with ARF in multiorgan failure (group II), have been treated. In 33 patients of group I standard bicarbonate hemodialysis was used, while acetate-free biofiltration was used for the others. In group II, 42 patients have been treated by continuous arteriovenous hemofiltration and 34 patients by daily recycled bicarbonate hemodialysis. Our data show that acetate-free biofiltration and bicarbonate dialysis were both highly dependable, but acetate-free biofiltration was better tolerated. Continuous arteriovenous hemofiltration is the method of choice in high-risk patients; daily bicarbonate hemodialysis is preferable only in patients with hemorrhagic diathesis. The average survival time is 55.2% with a statistically significant difference between groups I and II, while no difference has been observed within the same group according to the procedure.

Plasmapheresis versus plasma perfusion in acute Guillain-Barré syndrome.

Guillain-Barré Syndrome (GBS) is an acute post infectious or disimmune illness that affects nerve roots and peripheral nerves. Multicenter studies have clearly shown that plasma exchange (PE) provides valuable amelioration of GBS. It was recently suggested that plasma perfusion (PP) on phenylalanine columns displays the same therapeutic effects of PE in neuroimmunologic disorders, without the infectious risks linked with plasma replacement. In this study, the authors compared the efficacy of PE versus that of PP in two groups of patients suffering from GBS by investigating the clinical outcomes and the electrophysiologic and cerebrospinal fluid findings. Of 22 patients suffering from GBS, 16 underwent seven sessions of PE in a mean time of 15 days (Group A). Six patients, showing the same clinical pattern, underwent three sessions of PP in a mean time of 10 days (Group B). Data reported in Group A show that PE: 1) stops the progressive worsening of the disease, 2) prevents the development of acute respiratory failure, 3) allows an early and significant clinical improvement with change in disability grade, and 4) improves motor conduction velocities and motor action potentials when recorded 45 days after the end of treatment. Data in Group B show that PP allows a slower and later improvement in disability grade, and electrophysiologic data recorded at the end of treatment was worse after 45 days. Finally, it may be concluded that PE has beneficial effects on GBS in terms of time of recovery, complication rate, and relapses. Plasma perfusion did not show the same results.

Isolated ultrafiltration in refractory heart failure on patients with Cooley's anemia.

Dilatative cardiomyopathy is a late complication of Cooley's anemia resulting in severe heart failure resistant to conventional medical treatment. Anemia, iron and fluid overload are the main causes of this disease entity. Four male patients (mean age 22.3 +/- 5.4 years) with Cooley's anemia associated heart failure--4th NYHA and fluid overload > 20% body weight--resistant to medical treatment, underwent isolated ultrafiltration (IU). During 90 minutes of treatment an average of 1750 +/- 850 ml of fluid were removed using AN69S plate membrane. Each patient received an average of 7 IU sessions (range 4-13). Cardiac function was assessed before and after each session with echocardiography, venous cardiac catheterization and impedence cardiography. Transient cardiac improvement was observed after each IU session: left ventricular systolic diameter decreased, as did central venous pressure and pulmonary wedge pressure, whereas cardiac index increased. All patients died of unrelated causes. In conclusion IU treatment in dilatative cardiomyopathy resistant to conventional medical treatment in Cooley's anemia patients produces only transient cardiac improvement, but no improvement in overall survival.

Acetate-free biofiltration in acute renal failure.

Hemodialysis treatment for acute renal failure is associated with a high incidence of adverse reactions. Hemodynamic stability and adequate correction of acid-base and hydroelectrolyte imbalance are the main goals of dialytic strategy in acute renal failure. However, the variety of etiology and the diversity of clinical conditions suggest that individualized treatment may be advisable. To this purpose, in 26 patients suffering from "isolated" acute renal failure of different etiologies, we have used acetate-free biofiltration. We have performed 411 dialyses with an extremely low incidence of symptomatic treatments and remarkable cardiovascular stability. Correction of fluid, electrolyte, and acid-base imbalance proved excellent. Dialytic efficacy proved adequate. Our data show that acetate-free biofiltration is an easy technique suitable for individualized treatment and adaptable to changing needs during hemodialysis in patients with isolated acute renal failure.