High-dose calcitriol therapy and progression of cardiac vascular calcifications.

BACKGROUND: Dialysis patients show a very high prevalence of cardiovascular complications, affected as they are with abnormal and accelerated vascular calcifications and, eventually, calcium and phosphorous metabolism disorders. Multislice computed tomography (MSCT) provides a reproducible, high-resolution imaging of calcium contained in cardiac arteries, measured by Agatston score. The aim of the present study was to evaluate the influence of high-dose and low-dose calcitriol therapy on the progression of cardiac vascular calcifications in dialyzed patients. METHODS: We enrolled 36 dialyzed patients in a prospective study, including an interventional period of 12 months and a follow-up period of 12 months. Eighteen protocol patients received intravenous pulses of high-doses calcitriol at the end of dialytic treatment and sevelamer hydrochloride therapy. Control patients received low-dose calcitriol and sevelamer hydrochloride as well. Two MSCT scans were performed: 1 at the start of the study and 1 at the end of follow-up, and Agatston score was calculated at both examinations. RESULTS: At first examination, protocol patients showed almost the same level of cardiac vascular calcification as control patients. At the second MSCT, statistically significantly higher values of Agatston score were recorded for all patients. Indeed, patients who showed higher baseline values developed worse calcifications as recorded at the end of follow-up, both in the protocol and control group. CONCLUSIONS: Our data show that baseline level is strongly predictive of vascular calcification progression, and, moreover, there is no association between calcitriol administered doses and the progression of cardiac vascular calcification.

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.

Cardiac calcium evaluation in hemodialysis patients with multisection spiral computed tomography.

AIM: The aim of this study is cardiac calcium content evaluation in hemodialysis patients by a new technique, based on ultrafast multisection CT (MTC). METHODS: The study was carried out on 30 HD patients, 14 F and 16 M, average age 57.7 +/- 13.9 years, average HD age 57.3 +/- 47.4 months. The intact PTH levels were 625.4 +/- 571 pg/mL. Serum calcium, phosphate and CaxP product were 9.75 +/- 0.84 mg/mL, 6.21 +/- 1.01 mg/dL and 60.2 +/- 10.7 mg2/dL2, respectively. RESULTS: The values obtained with the MTC technique were reported in terms of Agatson scores. Score values frankly in the pathologic range (>100) were found in 24 patients (80%). Correlation analysis has shown positive and significant correlation coefficients of the score with patients' age (p = 0.003), serum calcium (p = 0.012), CaxP (p = 0.015), iPTH (p = 0.049), and borderline, to HD age (p = 0. 06). CONCLUSION: Risk factors for cardiac calcification are mainly age, degree of hyperparathyroidism, increased CaxP and serum calcium levels. A control of calcium phosphate parameters in hemodialysis patients seems to be mandatory to avoid increased severity of coronary artery disease.

[Italian study on the treatment of anaemia in chronic dialysis patients switched over to less frequent doses of darbepoetin from human recombinant erythropoietin (rHuEPO)]. / Studio italiano sul trattamento dell'anemia in pazienti in terapia dialitica sostitutiva con darbepoetina alfa con una minore frequenza di somministrazione della dose rispetto all'eritropoietina ricombinante umana (rHuEPO).

BACKGROUND: Darbepoetin alpha is a novel erythropoiesis stimulating protein with unique properties as compared to recombinant human erythropoietin (rHuEPO), including a three-fold longer elimination half-life that allows for less frequent dosing. This study was aimed at testing the efficacy and safety of darbepoetin alpha in a large number of chronic dialysis patients switched from rHuEPO. METHODS: Nine hundred and fifty dialysis patients in stable treatment with rHuEPO were switched to darbepoetin alpha. Patients receiving rHuEPO 2 or 3 times weekly were switched to once weekly darbepoetin alpha and those receiving rHuEPO once weekly were switched to once every other week darbepoetin alpha. Patients received darbepoetin alpha by the same route of administration (SC or IV) as the one used for rHuEPO. The unit doses of darbepoetin alpha (10-150 microg) were titrated to maintain haemoglobin concentration within -1.0 and +1.5 g/dL of the individual mean baseline haemoglobin levels and between 10 and 13 g/dL for 24 weeks. RESULTS: The mean change in haemoglobin from baseline to the evaluation period (weeks 21-24) was statistically but not clinically significant [-0.10 g/dL (95% CI: -0.18, -0.02]. In general, the geometric mean weekly dose of study drug from screening/baseline to evaluation period remained substantially unmodified [(from 26.10 micro g/wk to 25.90 microg/wk; percentage change -0.40% (95% CI: -3.78, 3.10)]. Overall, darbepoetin alpha was well tolerated. CONCLUSIONS: The treatment of anaemia of a large dialysis patient population with unit dosing of darbepoetin alpha is effective and safe in maintaining target haemoglobin concentration at reduced dose frequency.

[Clinical experience in HFR with a new resin-only sorbent cartridge]. / Sperimentazione clinica in HFR di una cartuccia rigenerante priva di carbone.

Adsorbent therapies have become increasingly popular over the last several years as they permit an additional method to selectively or non-selectively remove toxins. Adsorbents offer a unique removal strategy as they have an extremely high adsorption capacity due to their great surface area. This paper describes experiments that utilized a synthetic divinylbenzene styrenic resin cartridge to remove uremic toxins from chronic renal failure patients. The resin-only cartridge was tested as an alternative after a small number of patients (primarily taking ACE inhibitors) experienced gastrointestinal problems using hemodiafiltration with on-line regeneration (HFR). Subsequent laboratory evidence suggested that the particular carbon used in the cartridge was able to activate contact phase activation. This could potentially cause problems in patients taking ACE inhibitors, as they are unable to degrade bradykinin efficiently. The resin-only cartridge was tested in at 6 centers throughout Italy and included patients that had experienced previous reactions to the carbon-resin cartridge. At the conclusion of the study, no adverse reactions were reported and the cartridge exhibited excellent removal of b2 microglobulin and angiogenin.

[Arteriovenous brachio-basilic fistula as hemodialysis port. Original technique and long term results]. / La fistola artero-venosa brachio-basilica come accesso per emodialisi. Tecnica originale e risultati a distanza.

The authors report a prospective series of patients with-long term vascular access for chronic hemodialysis fashioned with a transposed brachio-basilic fistula. Over a three-year period (1998-2000), 14 patients underwent creation of the arteriovenous fistula. Demographic and clinical data were registered and a length of follow up more than 12 months was in all cases obtained. Of the 14 fistulas performed, 7 were successfully used for dialysis without complication. In seven patients late revision of fistulas was performed. The primary and secondary patency actuarial rates at two years were 50% and 75% respectively. The results of this series highlight as the basilic vein fistula provides reliable vascular access for chronic hemodialysis therapy. The low cost and the low morbidity rates suggest the brachial artery-transposed basilic vein fistulas as a valuable part of vascular access history of patients with chronic renal failure.

Surgery versus interventional radiology in the management of thrombosed vascular access for hemodialysis.

Thrombosis is the most frequent complication occurring in vascular access (VA). The two widely used treatment strategies for thrombosed VA are surgical and endovascular. Which is the best and whether different approaches should be used on proximal versus distal VA, is still debated. This is a retrospective study. Over a three years period, we studied among a population of 475 dialysis patients, 54 VA thromboses in 46 patients. Surgical procedure was successful in 14/17 (82%) distal artero-venous fistulas (AVF) while, in 9 proximal AVF, it led to initial success in 6 patients (66%), with a six months primary patency respectively of 93% and 84%. Radiological procedure resolved 6/10 distal AVF (initial success 60%) with primary patency of 66%, and was successful in 16/18 proximal AVF (initial success 89%) with primary patency of 81%. Taking our data all together, no differences are found between two thrombolitic (surgical and endovascular) procedures. But results were different in thrombosed proximal VA (where endovascular treatment should be preferred) versus distal ones (where surgery seems better).

Late symptomatic venous stenosis in three hemodialysis patients without previous central venous catheters.

It is well known that catheters placed in the subclavian or internal jugular veins may develop stenosis in the vein in which the catheter lies. Because the arteriovenous fistula (AVF) relies on good venous outflow, patients with ipsilateral central venous stenosis are subject to the malfunctioning of AVF. Until now, no data were published on patients showing central vein stenosis (CVS) without a previous central venous catheter (CVC) or a pacemaker. In this article, we report on 3 hemodialysis patients manifesting CVS ipslateral to AVF. None of these patients previously had undergone CVC. The stenosis observed had characteristics and symptoms similar to those observed in stenoses consequent to CVC. We concluded that CVS also may occur in subclavian or axillary veins proximal to a working AVF in hemodialysis patients who have never had a CVC and in the absence of compressive phenomena.

Low levels of hepatitis C virus RNA in blood of infected patients under maintenance haemodialysis with high-biocompatibility, high-permeability filters.

BACKGROUND: Patients undergoing maintenance haemodialysis are often infected with hepatitis C virus, yet the clinical course of liver disease is usually mild. We investigated whether the hepatitis C virus viral load is influenced by the haemodialytic procedure and the type of dialyser. METHODS: Hepatitis C virus-RNA levels were measured using a quantitative polymerase chain reaction assay in predialysis blood from 51 hepatitis C virus-infected patients dialysed with different membranes. Paired pre- and post-dialysis measurements were also obtained in 18 patients. RESULTS: Patients dialysed using cuprammonium-regenerated cellulose membranes with low (cuprofan) or intermediate (cellulose acetate or diacetate) biocompatibility had higher pre-dialysis hepatitis C virus-RNA levels (p<0.05] compared to those dialysed with synthetic high-biocompatibility, high-permeability polymeric membranes (polyacrylonitrile, polysulfone, polymethylmethacrylate or polycarbonate). Hepatitis C virus-RNA levels were unrelated to the duration of haemodialysis and the presence of abnormal transaminases. A significant reduction (p=0. 04) of serum hepatitis C virus-RNA levels was observed after a single haemodialysis, particularly in patients with high pre-dialysis viral load. Patients with low pre-dialysis hepatitis C virus-RNA levels (<2. 5 x 10(3) copies/ml) exhibited only minimal changes following the procedure. Four patients with medium-high basal viral load switched from a low-biocompatibility/low-permeability to a high-biocompatibility/high permeability filter had a marked reduction of viraemia after three weeks, in one case followed by a new increase after return to the original filter. CONCLUSIONS: Haemodialysis with high-biocompatibility/high-permeability filters in hepatitis C virus-infected patients is associated with low blood levels of hepatitis C virus-RNA. This finding may be of clinical relevance, especially in patients listed for kidney transplantation.

Femoral catheters: safety and efficacy in peripheral blood stem cell collection.

Central venous access is necessary in patients candidate for peripheral blood stem cell (PBSC) collection. We report our experience with a dual lumen femoral catheter (Gamcath, 11 french), initially designed for hemodialysis. We studied 147 patients and performed 488 collections after mobilization with either G-CSF alone or chemotherapy + G-CSF, when the white blood cell count exceeded 1 x 10(9)/L, or when a measurable population of CD34+ cells (20/microL) was detected in peripheral blood. All patients received systemic anticoagulation with a low weight heparin and ultrasound examination was performed after the removal of the catheter. Seven patients developed thrombosis (4.7%), ten experienced hematomas at the site of catheter placement (6.8%) despite prophylactic platelet transfusions, while only one patient (0.6%) had a catheter-related infection. In conclusion, the short-term use of large bore femoral catheters in setting up PBSC collection seems to be associated with minimal risk of infection and low thrombotic incidence.

Red blood cell membrane lipid peroxidation and resistance to erythropoietin therapy in hemodialysis patients.

BACKGROUND: Chronic hemolysis, inadequate production of erythropoietin (EPO) or an impaired response of erythroid stem cells to EPO are the main factors of anemia in end-stage renal disease (ESRD) patients. Oxidative damage of red blood cell (RBC) membrane is a well-established cause of chronic hemolysis in hemodialysis (HD) patients. Administration of high-dose recombinant human EPO (rHuEPO) fails to correct anemia in 5 to 10% HD patients although all established factors of resistance to rHuEPO therapy have been previously ruled out or corrected. PATIENTS AND METHODS: We investigated the degree of RBC membrane oxidative damage in 9 HD patients who failed to respond to maximal rHuEPO administration (more than 200 UI/Kg weekly for 4 months consecutively, group A), compared to 10 patients who showed a good response to standard rHuEPO therapy (group B) and to 10 patients who needed no treatment (group C). RBC malondialdehyde (MDA) was assumed as the index of oxidative stress in erythrocyte membrane. RESULTS: No significant difference in erythrocyte MCV and MCHC, iron status, parathyroid function, aluminum and dialysis-related blood loss was observed between patients of group A, B and C. RBC MDA, reticulocyte count, plasma-free hemoglobin (fhb) and serum lactate dehydrogenase (LDH) were significantly higher while plasma haptoglobin was significantly lower in patients of group A compared to patients of groups B and C. Moreover, a significant inverse relationship was observed between RBC MDA and either plasma hemoglobin, RBC count and hematocrit when all patients were evaluated together. CONCLUSION: In conclusion, increased oxidative damage of RBC membrane is often detectable in HD patients who fail to respond to rHuEPO administration even in the absence of all established factors of resistance to EPO. Peripheral response to rHuEPO may be normal in these patients and persistent anemia may be related to enhanced hemolysis due to oxidative stress. Oxidative damage itself may therefore be considered a factor of resistance to EPO.

The treatment of severe forms of myasthenia gravis.

In this study we introduced and tested the clinical efficacy of a combined treatment based on the association of plasma exchange (PE) with high daily doses of prednisone in 18 patients with severe forms of myasthenia gravis (MG). A myasthenic score based on strength and resistance was evaluated in each patient in basal condition and during the treatment. The study design included 5 sessions of PE, performed within a period of 15 days, 1 session every 3 days, associated with administration of oral prednisone (1 mg/kg of body weight), which began at the same time as the first session and was continued following a daily schedule for at least three months. A significant improvement was obtained from the start of the therapy, with a reduction of the myasthenic score from 26.56 to 11.44 by day 10 and with further reduction after PE interruption. An early improvement, recorded within 24-48 hours of the beginning of the study design, was observed in 11/18. The administration of steroid therapy was never followed by a worsening of myasthenic symptoms (as reported when it is administered in the absence of concomitant PE). No recurrence of symptoms was reported after 29 months' follow-up. This type of therapeutic association was generally well tolerated and no unwanted side effects were observed. According to our results we can conclude that medium-high doses of oral prednisone in simultaneous association with PE lead to a successful control of severe forms of MG and may be considered a valid therapeutic strategy.

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.

Plasmapheresis in severe forms of myasthenia gravis.

In this study we introduce a new combination treatment of plasma exchange (PE) and high daily doses of prednisone for severe forms of myasthenia gravis (MG). The clinical efficacy of the combined therapy has been tested in 18 patients suffering from severe forms of MG. The protocol included 5 sessions of PE, performed in a range of 15 days, 1 session every 3 days, with concurrent administration of oral prednisone (1 mg/kg of body weight), starting at the first session of PE and given daily for at least 3 months. At the end of the entire cycle of PE, almost complete recovery (more than 90% of the initial clinical score) was obtained in 8 of 18 patients while an improvement between 60 and 90% of the initial score was achieved in 9 of 18 patients. An early improvement was noted 24 h after the beginning of plasmapheresis in 11 of 18 patients. No recurrence of symptoms was reported after 36 months of follow-up for 17 patients. The administration of steroid therapy was never followed by an early exacerbation of myasthenic symptoms as reported when it is administered in the absence of concomitant PE. According to our results, we can conclude that high doses of oral prednisone therapy in simultaneous association with PE lead to successful control of severe forms of MG, significantly superior to the therapeutic strategies until now adopted and reported in literature.

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.