Blood thiol status and erythrocyte glutathione-S-transferase in chronic kidney disease patients on treatment with frequent (daily) hemodialysis.

BACKGROUND: Chronic kidney disease (CKD) is a condition of impaired homeostasis of blood thiols characterized by a severe hyperhomocysteinemia (HH) and abnormal expression of the red blood cell glutathione (GSH)-consuming enzyme GSH S-transferase (eGST) (Galli et al., Clin Chem 1999). The correlation between plasma Hcy and eGST recently identified by our group (Dessì et al., Amino Acids 2012) suggests a role of this detoxifying enzyme in the impaired thiol status of CKD treated with hemodialysis therapy (HD). This retrospective study is aimed at investigating whether frequent HD can alleviate these biochemical symptoms of CKD. METHODS: Laboratory data of a population of 98 HD patients investigated for plasma Hcy and blood thiol status between 1999 and 2004 were examined. A frequent HD method carried out with a 2-h daily schedule (daily HD) (DHD) was compared with standard 4-h × 3/week protocol of HD (SHD) in either cross-sectional (n = 70 SHD vs. n = 28 DHD) and prospective A-B design (n = 18 SHD patients shifted to DHD). RESULTS: The results demonstrate that DHD produces a better correction than SHD of the uremic retention solute Hcy as well as of Cys and Cys-Gly measured in plasma. Such a correction effect of DHD on HH correlates with that on the detoxification enzyme eGST and on pGSH. CONCLUSIONS: These findings point to a role of frequent dialysis in the depuration of uremic retention solutes that may interfere with thiol metabolism and redox in HD patients. These solutes may include substrates of eGST that await further investigation for molecular identification and better removal by more efficient dialysis therapies.

Effect of two-hour daily hemodialysis and sham dialysis on breath isoprene exhalation.

BACKGROUND: Isoprene, a volatile hydrocarbon produced by the human organism, is currently being extensively investigated because the mechanisms underlying its endogenous origin are unknown and because experiments suggest it is toxic and cancerogenous. Previous reports of increases in breath isoprene concentrations during 4-hour, thrice-weekly hemodialysis, but not during continuous ambulatorial peritoneal dialysis, prompted us to assess the behavior of isoprene in another dialytic modality, i.e., short daily hemodialysis (short DHD). Furthermore, in order to determine whether removal of solutes and/or contact of blood with the dialytic membrane influenced the metabolism of isoprene, we performed a sham short hemodialysis session in a subgroup of 8 patients (sham short HD), i.e., with blood flowing through a dialyzer but without dialysate and ultrafiltration. METHODS: The present study evaluates the effects of a two-hour short DHD and a two-hour session of sham HD on isoprene breath levels, as determined by gas chromatography before, during and after sessions. Parallel analyses of ambient air and monitoring of blood pressure and heart rate were performed. RESULTS: Both short DHD and sham DHD induced an increase in breath isoprene exhalation in all patients without being associated with significant hemodynamic variations. CONCLUSION: These findings suggest that the increase in breath isoprene after a session of hemodialysis is neither a reaction to mevalonate depletion nor to metabolic variations induced by the depurative effect, because these changes do not occur during sham HD. It is not related to hemodynamic changes because none were observed in this experimental model. The isoprene increase seems to be of metabolic origin and appears to be connected in some way with the extracorporeal circuit. These interesting findings provide a further impulse to study the biosynthetic pathways involved and to investigate the medical and biological significance of isoprene in humans.

[Acute renal failure, hemolysis and thrombocytopenia]. / Un caso di insufficienza renale acuta associata ad emolisi e piastrinopenia.

A 41-year-old male was admitted because of severe systemic hypertension and acute renal failure (ARF) that required hemodialysis (HD). Also present were hemolytic anemia, thrombocytopenia and increased plasmatic levels of aldosterone and reninic activity. The diagnostic tests performed during the recovery led to the conclusion of malignant hypertension. This case dealt with a cause of ARF, which is not currently so common; physicians should be aware of this condition especially when it is present with hemolytic anemia and thrombocytopenia, which are the microangiopathy markers.

A randomized trial of steroid avoidance in renal transplant patients treated with everolimus and cyclosporine.

In this randomized trial renal transplant recipients were treated with basiliximab, everolimus 3 mg/day, low-dose CsA. At transplantation, patients were randomized to stop steroids at the seventh day (group A) or to continue oral steroids in low doses (group B). Of the 113 patients enrolled, 65 were randomized to group A and 68 to group B. All patients were followed for 2 years. During the study 28 (43%) group A patients required reintroduced corticosteroids. One patient died, in group B. The Graft survival rate was 97% in group A and 90% in group B. There were more biopsy-proven rejections in group A (32% vs 16%; P = .044). The mean creatinine clearance was 54 +/- 21 mL/min in group A vs 56 +/- 22 mL/min in group B. Mean levels of serum cholesterol tended to be lower in group A, but the difference was of borderline significance (191 +/- 91 vs 251 +/- 188 mg/dL; P = .07). Vascular thrombosis (0 vs 5) and pneumonia requiring hospitalization (2 vs 7) tended to be more frequent in group B. Only three cases of CMV infection (1 vs 2) occurred. An immunosuppressive therapy with everolimus and low-dose CsA allows one to obtain excellent renal graft survival and stable graft function at 2 years. Early interruption of steroids in patients treated with this regimen may increase the risk of acute rejection, but neither affects graft survival nor graft function, while possibly reducing the risk of hyperlipemia and vascular thrombosis. About 60% of patients given everolimus and low-dose CsA can definitively stop steroids after 1 week.

Accumulation of vitamin E metabolites in the blood of renal failure patients.

BACKGROUND & AIMS: Carboxyethyl-hydroxychromans (CEHC) are hydrosoluble vitamin E metabolites excreted through the renal filter. In this study we investigated the effect of the kidney damage on the blood levels of CEHC. METHODS: Plasma levels of alpha-CEHC, gamma-CEHC and their precursors (namely, alpha-tocopherol and gamma-tocopherol) were measured by HPLC with electrochemical detection in chronic (CRF) and end-stage renal failure patients on regular hemodialysis (HD) before and after dialysis. CRF patients (n = 26) were divided into three subgroups with different extent of kidney damage as measured by the intervals of creatinine clearance (CrCl, in ml/min): (a) 2-10, (b) 10-20, and (c) 20-45. HD patients (n = 8) did not show residual renal function. In all the subjects the intake of vitamin E (as alpha-tocopherol) was assessed using a food frequency questionnaire. In the HD group, the plasma concentrations of ascorbic and uric acid (AA and UA, respectively), total thiols, the total antioxidant status (TAS) and reactive carbonyls were also measured. RESULTS: The progressive deterioration of the kidney function in the different groups of patients produced an exponential increase of both alpha-CEHC and gamma-CEHC in plasma. Compared with healthy controls (alpha-CEHC = 20.1+/-13.4 and gamma-CEHC = 230.6+/-83.0 nmol/l) the levels of CEHC approximately doubled in patients with CrCl < or = 20ml/min (42.4+/-20.2 and 424.5.5+/-174.4; P <0.05 or higher in both) and reached a 3-fold maximum increase in HD patients (77.3+/-45.7 and 636.6+/-219.3). The hemodialysis provided a significant, but only a transient, correction of CEHC accumulation (44.8+/-23.5, 364.2+/-189.9). The HD patients showed lower intake and levels of vitamin E (alpha-tocopherol = 5.1+/-1.0 and gamma-tocopherol =0.32+/-0.11 micromol/mmol cholesterol; P <0.05) compared to healthy controls (5.8+/-0.8 and 0.43+/-0.14), but in the CRF patients tocopherol levels were normal or only slightly decreased even though approximately half of the subject had lowered vitamin E intake. When the entire patient population was considered, the blood concentrations of parental tocopherols and CEHC did not correlate. The HD patients before dialysis showed a marked decrease of TAS/UA, AA and thiols levels, while UA and free carbonyls significantly increased. After dialysis, the depletion of AA and thiols further worsened and also UA and TAS/UA decreased, but free carbonyls slightly increased. CONCLUSIONS: The results other than to confirm the key importance of the renal route for the excretion of CEHC, demonstrate that CEHC cannot be reliably used to investigate vitamin E biokinetics and transformation without a careful examination of the renal function. CEHC accumulation does not seem to influence the antioxidant status in the plasma of HD patients. Further studies are requested to establish whether such an increase in blood CEHC concentrations might be harmful or could contribute to the biological functions of the vitamin E in uremia and dialysis patients.

Short daily hemodialysis: blood pressure control and left ventricular mass reduction in hypertensive hemodialysis patients.

Several retrospective and uncontrolled prospective studies reported blood pressure (BP) normalization and left ventricular mass (LVM) reduction during daily hemodialysis (DHD). Conversely, the burden of these major independent risk factors is only marginally reduced by the initiation of standard thrice-weekly dialysis (SHD), and cardiovascular events still represent the most common cause of death in hemodialysis patients. Therefore, we performed a randomized two-period crossover study to compare the effect of short DHD versus SHD on BP and LVM in hypertensive patients with end-stage renal disease. We studied 12 hypertensive patients who had been stable on SHD treatment for more than 6 months. At the end of 6 months of SHD and 6 months of DHD in a sequence of randomly assigned 24-hour ambulatory BP monitoring, echocardiography and bioimpedance were performed. Throughout the study, patients maintained the same Kt/V. A significant reduction in 24-hour BP during DHD was reported (systolic BP [SBP]: DHD, 128 +/- 11.6 mm Hg; SHD, 148 +/- 19.2 mm Hg; P < 0.01; diastolic BP: DHD, 67 +/- 8.3 mm Hg; SHD, 73 +/- 5.4 mm Hg; P = 0.01). The decrease in BP was accompanied by the withdrawal of antihypertensive therapy in 7 of 8 patients during DHD (P < 0.01). LVM index (LVMI) decreased significantly during DHD (DHD, 120.1 +/- 60.4 g/m(2); SHD, 148.7 +/- 59.7 g/m(2); P = 0.01). Extracellular water (ECW) content decreased from 52.7% +/- 11.4% to 47.6% +/- 7.5% (P = 0.02) and correlated with 24-hour SBP (r = 0.63; P < 0.01) and LVMI (r = 0.66; P < 0.01). In conclusion, this prospective crossover study confirms that DHD allows optimal control of BP, reduction in LVMI, and withdrawal of antihypertensive treatment. These effects seem to be related to reduction in ECW content.

Advanced glycation end products: specific fluorescence changes of pentosidine-like compounds during short daily hemodialysis.

BACKGROUND: Advanced glycation end products (AGE) accumulate in uremia and represent an important etiopathogenetic cause of morbidity in dialyzed patients. Conventional hemodialysis treatment seems to be ineffective in lowering AGE levels. We wished to investigate whether daily hemodialysis (DHD), a treatment that seems to result in better clinical condition in end-stage renal disease patients, is effective in the reduction of these compounds. METHODS: We evaluated 10 non-diabetic patients on standard hemodialysis (SHD = 3 x 4 h/week) for more than 6 months by a crossover study. These patients were assigned randomly to 6 months of DHD (6 x 2 h/week) or 6 months of SHD. Then, they were switched to 6 months of the alternative treatment. At the end of these two periods, we studied pentosidine-like AGE compounds by measuring the total fluorescence at a wavelength characteristic for these substances: Ex: 335nm/Em:385nm; we also measured protein-linked pentosidine at the same time points. Finally, we determined the AGE-related total fluorescence in the deproteinized serum of 13 uremic patients on peritoneal dialysis (CAPD) and of 10 healthy controls. RESULTS: Pre-HD AGE-related total fluorescence obtained after 6 months of DHD was significantly lower than that obtained with standard HD (DHD = 201.3 +/- 36.4 AU/ml vs. SHD = 267.5 +/- 141.4 AU/ml, p = 0.03). The extraction rate per minute of dialysis was slightly, but not significantly higher during DHD than SHD (0.29 +/- 0.11% vs. 0.23 +/- 0.04, p = 0.07). AGE-related total fluorescence pre-HD values in patients treated by SHD and DHD were about 20-fold higher than in control subjects. They did not differ from CAPD patients. The pre-dialysis level of protein-linked pentosidine was significantly lower in DHD than in SHD (DHD = 16.12 +/- 4.71 pmol/mg protein, SHD = 22.64 +/- 6.86 pmol/mg protein, p < 0.01). CONCLUSIONS: DHD showed a reduction in AGE-related total fluorescence, although the mean value remained higher than in control subjects. DHD is also accompanied by a decrease in protein-linked pentosidine.

Polymeric protein-polyamine conjugates: a new class of uremic toxins affecting erythropoiesis.

BACKGROUND: Preliminary evidence on the accumulation of polyamine-protein conjugates (PPCs) was obtained in uremic patients. The presence of these substances in the plasma of hemodialysis (HD) patients was evaluated, and their possible contribution to uremic anemia was investigated by testing the effect of PPC synthesized in vitro on erythroid cell proliferation. METHODS: Plasma PPC was measured by high-performance liquid chromatography. The in vitro synthesis of PPC from human plasma was carried out by means of the enzyme transglutaminase in the presence of either [3H]-labeled or unlabeled spermidine (SPD). After gel filtration chromatography and detection of the fractions containing [3H]SPD, the latter were tested for their effect on mononuclear bone marrow cell proliferation. RESULTS: In three out of four patients examined, mainly SPD-protein conjugates (SPD-PC) were observed to accumulate during HD. The levels ranged from 0.17 to 4.93 pmol/mg proteins before dialysis, and these values increased at 30 minutes and at the end of the dialysis up to levels 11.90 pmol/mg. SPD-PC levels in healthy controls were 1.46 +/- 0.82. SPD-PCs synthesized in vitro were recovered in two main fractions showing a molecular weight of> 100 kD (peak 1) and of approximately 30 to 50 kD (peak 3), respectively. The SPD-PC contained in peak 1 showed the greatest inhibitory effect on colony-forming units-erythroid (CFU-E) proliferation without any appreciable effect on burst-forming units-erythroid (BFU-E). CONCLUSION: We demonstrate that SPD-PC can accumulate in HD patients. These substances, which affect CFU-E proliferation, can be considered as an at yet unrevealed class of uremic toxins contributing to the onset of the uremic anemia.

Vitamin E, lipid profile, and peroxidation in hemodialysis patients.

BACKGROUND: Hypertriglyceridemia, lipid peroxidation, and abnormalities of the plasma fatty acid (PUFA) profile may be important risk factors for the atherosclerotic cardiovascular disease in hemodialysis (HD) patients. METHODS: We investigated how these factors are affected by vitamin E supplementation carried out by oral administration (clinical study 1) and dialysis with vitamin E-modified dialyzers (clinical study 2). RESULTS: In the HD patients, conditions of relative vitamin E deficiency were observed [lowered vitamin E/triglyceride (TG) ratio] in the presence of high levels of thiobarbituric acid reactants (TBARs) and decreased levels of the polyunsaturated fraction of PUFAs paired with an increased amount of monounsaturated ones (MUFA). In both studies, vitamin E supplementation significantly increased the levels of vitamin E in the plasma without affecting TG levels and provided a partial correction of TBAR levels. Of note was the relative increase in the PUFA fraction, which gave solid proof of an anti(per)oxidant effect of vitamin E supplementation in HD patients. Vitamin E supplementation was also observed to increase plasma levels of reduced glutathione and NOx (NO2 + NO3). CONCLUSION: The results suggest that vitamin E supplementation may be an effective accessory therapy to combat oxidative stress-lowering lipid peroxidation in HD patients.

In vitro study of the efficacy of a two-way connection with disinfectant in the prevention of peritonitis.

A new connection system for continuous ambulatory peritoneal dialysis (CAPD) has been established, and its efficacy in preventing microbial contamination of the peritoneal cavity has been tested in vitro. The system consists of a Y-shaped channel formed in the bottom of a Plexiglas cup. The Luer-lock shaped ends of the Y-shaped channel are designed to host the connectors from the drainage bag, the catheter transfer set, and the bag of fresh dialysate. Because the connectors from the catheter transfer set and the fresh bag are located at the inner surface of the cup bed, and because the cup is filled with disinfectant during the entire exchange procedure, all at-risk steps are continuously protected by disinfectant (that is, removal of the caps from the connectors, connection and disconnection, replacement of the caps). Still, because the patient could inadvertently extract and contaminate one of the two connectors (although such a possibility is unlikely), the disinfecting efficacy of the system was tested in vitro. Despite contamination with various micro-organisms at the highest possible concentrations, all tests showed negative bacterial growth, thus confirming the absolute efficacy of the system in preventing exogenous transluminal peritonitis.

ANCA in dialysis patients: a role for bioincompatibility?

UNLABELLED: BACKGROUND. Anti-neutrophil cytoplasmic autoantibodies (ANCA) have been described in patients suffering from systemic vasculitis such as Wegener granulomatosis, microscopic polyangiitis, Churg-Strauss syndrome and other pathological conditions. In this paper we report a greater incidence of ANCA in hemodialysis patients as compared to peritoneal dialysis patients, pre-dialytic uremic patients and non-renal patients; a possible role for dialysis bioincompatibility in ANCA generation was also investigated. METHODS: A total of 335 uremics in substitutive treatment (176 in hemodialytic treatment and 159 in peritoneal dialysis) were examined for ANCA positivity. A total of 189 patients with advanced renal failure in conservative treatment and 100 healthy subjects were used as control. The dialysis techniques were standard hemodialysis (n = 119), low volume hemodiafiltration (n = 26) and hemofiltration (n = 31). ANCA positivity was examined by immunofluorescence (IF): diffuse finely granular staining was considered as classical positive reaction (C-ANCA) and P-ANCA was diagnosed if a perinuclear staining was observed. EIA for proteinase-3 (anti PR-3) and myeloperoxidase-antibodies (anti-MPO) were also performed. RESULTS: In non-renal patients and in patients with pre-dialytic renal insufficiency none were found ANCA positive. In peritoneal dialysis patients all but one were ANCA negative with IF, with all EIA test resulting negative. In hemodialytic patients, a positive IF test was found in 26 (14.7%) for P-ANCA and in 5 (2.8%) for C-ANCA; using the EIA test 23 (13%) patients were positive for MPO and 12 (6.8%) for PR-3. CONCLUSIONS: No correlation with age, primary renal diseases, dialytic age, dialysis membrane materials was found; regarding the different extracorporeal dialytic techniques a higher incidence (p < 0.02) was detected in patients undergoing HDF Backfiltration of contaminated dialysate may induce ANCA via an increased cytokine generation.

Survival of vascular access during daily and three times a week hemodialysis.

AIM: A major cause of morbidity for hemodialysis patients is vascular access failure and/or occlusion. It is commonly believed that an increased frequency of dialysis sessions, among other factors, might lead to a higher rate of fistula complications. MATERIALS AND METHODS: To evaluate if patients on daily hemodialysis carry a higher risk of vascular access occlusion, we examined the incidence rate of access occlusion and the survival function of native vascular accesses in patients undergoing daily dialysis (DD; n = 24) as compared to patients on standard three times a week hemodialysis (TWD; n = 124). RESULTS: The mean follow-up time was 3.6 years. In the TWD group 42 patients had a first-access closure, whereas only 2 patients out 24 had a similar event in the DD group. The proportion of first-access closure was 33.9% for TWD and 8.3% for DD (p < 0.01). The incidence rate was 9.8 (95% CI: 7.2 -13.2) and 2.2 (95% CI: 0.4 - 7.1) events per 100 patient-years for TWD and DD, respectively. The rate difference was 7.6 (95% CI 3.4 - 11.9) events per 100 patient-years, and the unadjusted risk ratio was 4.5 (95% CI: 1.2 - 16.9; p < 0.01). The mean vascular access survival before closure was 3.3 years in TWD and 3.7 years in DD. Survival curves, obtained considering the first-access closure as the endpoint, showed a significant difference between DD and TWD (log-rank 5.16; p < 0.05). In a Cox-proportional hazard model the relative risk (RR) of vascular-access closure in TWD remained significant (RR = 4.3; 95% CI 1.1 - 18.2) after adjustment for age. CONCLUSION: The results of this observational study, conducted on a limited number of DD patients, suggest that daily dialysis might not have an adverse prognostic significance for access closure.

Overexpression of erythrocyte glutathione S-transferase in uremia and dialysis.

BACKGROUND: Overexpression of glutathione S-transferase (GST; EC 2.5. 1.18) has been documented in the erythrocytes of patients with chronic renal failure, and this event may well be of relevance from a clinical standpoint. In fact, it could serve as a marker of uremic toxicity overall, which can contribute to impair the function and survival of the erythrocytes. However, the biochemical details of this phenomenon are poorly understood. METHODS: In this study, we characterized the expression of GST in erythrocytes of 118 uremic patients under different clinical conditions. The mechanisms responsible for the regulation of protein expression and enzyme activity were investigated in light of different dialysis approaches, oxidative stress, uremic toxins, erythrocyte age, and erythropoietin (EPO) supplementation. RESULTS: Mean GST activity in uremic patients was highly overexpressed with respect to controls, and this phenomenon was exclusively attributable to an increased expression of GST. Overexpression of GST did not appear to be dependent on oxidative stress and was not influenced by vitamin E supplementation. In the same manner, both erythrocyte age and EPO supplementation apparently did not interfere with the GST concentrations, which were the same in controls and patients. Preliminary experiments suggested that high-molecular weight or protein-bound toxins could play some role in the overexpression of GST. CONCLUSIONS: GST expression may be a useful marker for the individual accumulation of uremic toxins as well as of the efficiency of new dialysis strategies in removing them.

Biological effects of oxidant stress in haemodialysis: the possible roles of vitamin E.

Oxidative stress has been proposed to play a role in many disease states, including cardiovascular and infectious diseases, cancer, diabetes and neurodegenerative pathologies. The fact that these diseases have an increased incidence in uremia, and particularly in dialysis patients, suggests an increased exposure to oxidative stress in this condition. In haemodialysis (HD), the absence of a complete correction of the uremic toxicity together with the untoward effects of the dialysis, malnutrition and the progressive worsening of the clinical condition, can lead to a high susceptibility to oxidative stress by an abnormal production of oxidants - including reactive oxygen species (ROS) and uremic toxins with prooxidant function - and defective antioxidant protection. One of the most investigated biological effects of the oxidative stress in the HD patients is lipid peroxidation in plasma and blood cell membranes. Moreover, we have recently described how abnormal apoptosis in peripheral blood leukocytes is associated with cell oxidative stress (intracellular thiol depletion). Vitamin E, in both in vitro and in vivo conditions, has been proposed to partially correct these effects. In this review we evaluated some features of two new dialysis strategies using an antioxidant approach to the protection against the oxidant stress in HD. Their rationale is based on the emerging role of vitamin E in counteracting some biological effects associated with oxidant stress namely lipid peroxidation and apoptosis. These techniques use: 1) the recirculation of the dialysate through a suspension of vitamin E-enriched liposomes combined with the supplementation by the dialysate with ascorbic acid, this method has been called hemolipodialysis; 2) the coating of the dialysis membrane with vitamin E (vitamin E- modified dialysis membranes). These unconventional approaches to the antioxidant therapy in HD open a widely unexplored and promising field in the evolution of the biomaterials and dialysis quality.

Clinical and biochemical correlates of starting "daily" hemodialysis.

BACKGROUND: Daily hemodialysis has been proposed to improve outcomes for patients with end-stage renal disease. There has been increasing evidence that daily hemodialysis might have potential advantages over intermittent dialysis. However, despite these potential advantages, daily hemodialysis is infrequently used in the United States, and published accounts on the technique are few. METHODS: We describe patient outcomes after increasing their hemodialysis frequency from three to six times per week in a cohort of 72 patients treated at nine centers during 1972 to 1996. Analyses of predialysis blood pressure and laboratory parameters from 6 months before until 12 months after starting frequent hemodialysis used a repeated-measures statistical technique. RESULTS: Predialysis systolic and diastolic blood pressures fell by 7 and 4 mm Hg, respectively, after starting frequent hemodialysis (P = 0.02). Reductions were greatest among patients being treated with antihypertensive medications, despite a reduction in their dosage of medications. Postdialysis weight fell by 1.0% within one month of starting frequent hemodialysis and improved control of hypertension. After the initial drop, postdialysis weight increased at a rate of 0.85 kg per six months. Serum albumin rose by 0.29 g/dl (P < 0.001) between months 1 to 12 of treatment with daily hemodialysis. Hematocrit rose by 3.0 percentage points (P = 0.02) among patients (N = 56) not treated with erythropoietin during this period. Two years after the start of daily hemodialysis, Kaplan-Meier analyses showed a patient survival of 93%, a technique survival of 77%, and an arteriovenous fistula patency of 92%. Vascular access patency was excellent despite more frequent use of the access. CONCLUSIONS: These results suggest that in certain patients, daily hemodialysis might have advantages over three times per week hemodialysis.

Left ventricular hypertrophy in daily dialysis.

Cardiac hypertrophy, a well-known independent risk factor for cardiovascular death, is a very frequent complication in ESRD patients. Its frequency tends to be even higher in dialyzed patients due to the fact that the current dialytic treatments are unable to keep under a satisfactory control the various responsible factors and particularly the blood pressure, which is largely the most important. Daily hemodialysis, a more frequent schedule consisting of 6-7 sessions/week lasting 2 or more hours, has definitely proved its superiority in controlling blood pressure and in improving anemia, and thus has the requisites for positively influencing cardiac hypertrophy. In fact, a series of studies, both retrospective and prospective, performed during the last years by our group, have confirmed that this new, more frequent and thus more physiological schedule, is able not only to stop the progression of the cardiac hypertrophy in uremic patients but also to revert toward the normality, in a relatively short time. This appears to be essentially a consequence of the excellent blood pressure control, which in turn derives from the easier control of the true dry weight, achievable with this type of dialytic treatment.