A novel methodology for personalized simulations of ventricular hemodynamics from noninvasive imaging data.

Current state-of-the-art imaging techniques can provide quantitative information to characterize ventricular function within the limits of the spatiotemporal resolution achievable in a realistic acquisition time. These imaging data can be used to personalize computer models, which in turn can help treatment planning by quantifying biomarkers that cannot be directly imaged, such as flow energy, shear stress and pressure gradients. To date, computer models have typically relied on invasive pressure measurements to be made patient-specific. When these data are not available, the scope and validity of the models are limited. To address this problem, we propose a new methodology for modeling patient-specific hemodynamics based exclusively on noninvasive velocity and anatomical data from 3D+t echocardiography or Magnetic Resonance Imaging (MRI). Numerical simulations of the cardiac cycle are driven by the image-derived velocities prescribed at the model boundaries using a penalty method that recovers a physical solution by minimizing the energy imparted to the system. This numerical approach circumvents the mathematical challenges due to the poor conditioning that arises from the imposition of boundary conditions on velocity only. We demonstrate that through this technique we are able to reconstruct given flow fields using Dirichlet only conditions. We also perform a sensitivity analysis to investigate the accuracy of this approach for different images with varying spatiotemporal resolution. Finally, we examine the influence of noise on the computed result, showing robustness to unbiased noise with an average error in the simulated velocity approximately 7% for a typical voxel size of 2mm(3) and temporal resolution of 30ms. The methodology is eventually applied to a patient case to highlight the potential for a direct clinical translation.

Towards a fast and efficient approach for modelling the patient-specific ventricular haemodynamics.

Computer modelling of the heart has emerged over the past decade as a powerful technique to explore the cardiovascular pathophysiology and inform clinical diagnosis. The current state-of-the-art in biophysical modelling requires a wealth of, potentially invasive, clinical data for the parametrisation and validation of the models, a process that is still too long and complex to be compatible with the clinical decision-making time. Therefore, there remains a need for models that can be quickly customised to reconstruct physical processes difficult to measure directly in patients. In this paper, we propose a less resource-intensive approach to modelling, whereby computational fluid-dynamics (CFD) models are constrained exclusively by boundary motion derived from imaging data through a validated wall tracking algorithm. These models are generated and parametrised based solely on ultrasound data, whose acquisition is fast, inexpensive and routine in all patients. To maximise the time and computational efficiency, a semi-automated pipeline is embedded in an image processing workflow to personalise the models. Applying this approach to two patient cases, we demonstrate this tool can be directly used in the clinic to interpret and complement the available clinical data by providing a quantitative indication of clinical markers that cannot be easily derived from imaging, such as pressure gradients and the flow energy.

Patient specific fluid-structure ventricular modelling for integrated cardiac care.

Cardiac diseases represent one of the primary causes of mortality and result in a substantial decrease in quality of life. Optimal surgical planning and long-term treatment are crucial for a successful and cost-effective patient care. Recently developed state-of-the-art imaging techniques supply a wealth of detailed data to support diagnosis. This provides the foundations for a novel approach to clinical planning based on personalisation, which can lead to more tailored treatment plans when compared to strategies based on standard population metrics. The goal of this study is to develop and apply a methodology for creating personalised ventricular models of blood and tissue mechanics to assess patient-specific metrics. Fluid-structure interaction simulations are performed to analyse the diastolic function in hypoplastic left heart patients, who underwent the first stage of a three-step surgical palliation and whose condition must be accurately evaluated to plan further intervention. The kinetic energy changes generated by the blood propagation in early diastole are found to reflect the intraventricular pressure gradient, giving indications on the filling efficiency. This suggests good agreement between the 3D model and the Euler equation, which provides a simplified relationship between pressure and kinetic energy and could, therefore, be applied in the clinical context.

[Peritoneal dialysis in cirrhotic patients]. / La dialisi peritoneale nei pazienti con cirrosi epatica.

Renal failure and the need for dialysis worsen the prognosis of patients with combined liver and kidney disease. The choice of an appropriate dialysis technique should improve the life expectancy of these patients. Hypotension, impaired defence against infections, electrolyte and acid-base imbalance, severe protein and caloric malnutrition, hyperammonemia, hyperbilirubinemia, and inadequate response to diuretics present a number of clinical problems in patients with liver insufficiency. Liver failure is therefore considered an important risk factor for any type of dialysis. Theoretically, both hemodialysis and peritoneal dialysis may cause specific problems in these patients. Hemodialysis has an increased cost/benefit ratio in cirrhotic patients. The administration of heparin during dialysis might worsen blood coagulation, ascites is not controlled by hemodialysis, and frequent paracentesis may be necessary. The efficiency of hemodialysis in removing certain toxic substances accumulating in liver failure is still unclear. Peritoneal dialysis does not require anticoagulation, helps maintain residual renal function, allows continuous removal of a fixed amount of ascitic fluid, does not cause acute hemodynamic changes, clears some of the toxic metabolites accumulated by liver failure, and is less expensive. Finally, peritoneal dialysis is associated with continuous absorption of glucose through the mesenteric capillaries into the mesenteric and liver blood flow, thus improving caloric malnutrition. During the first months of peritoneal dialysis, cirrhotic patients lose about 10 g of protein in the peritoneal dialysate but this loss tends to decrease with time. All the available data seem to indicate that in cirrhotic patients on peritoneal dialysis the majority of complications are consequent upon liver disease, which is also the most important cause of death. The outcome of peritoneal dialysis is not affected by cirrhosis and is similar to that observed in noncirrhotic patients. All the evidence reported in the literature seems to indicate that in cirrhotic patients peritoneal dialysis is an adequate treatment of uremia.

[Should dialysis be for all? Comment]. / Ma la dialisi deve essere per tutti? Commento.

Legal and ethical aspects of withholding or withdrawing dialysis are still matter or debate and it is impossible to present a course of action that would always be correct. Dialysis is an extraordinary, high cost and invasive treatment. Therefore the possibility to withhold or withdraw this treatment should be discussed in each single case, after evaluating comorbidities, expected survival, rehabilitation, quality of life, psychosocial cost and clinical complications. On these basis competent patients have the possibility to give or deny their consent to the treatment and to change this decision at any time. In incompetent patients doctor should try to understand what the patient would choose if he were competent or help family to decide what action would achieve the best interest of the patient. The Catholic Church considers it acceptable to withdraw or withhold extraordinary therapies whose final effect is a mere prolongation of survival with an unacceptably poor quality of life (no apparent therapeutic benefit). It is often inhumane to ask the family to decide to let a patient die. This should be a medical proposal to be accepted by the family after an appropriate information on possible alternatives. Finally palliative care and medical and social assistance should be provided to help the patient and his family.

[Evaluation of peritoneal catheters and connection systems in peritoneal dialysis]. / Valutare il catetere peritoneale ed i sistemi di connessione.

Evaluation of peritoneal catheters is based on the material, the number and type of cuffs, the length and intraperitoneal shape of the catheter, and its site of insertion. Final cost is another important issue which should take into account differences in the incidence of complications, in the number of hospitalizations, and in the simplicity of catheter insertion. Double-cuff catheters are used more than single-cuff catheters. The most commonly used catheter shapes are the classical Tenckhoff, the swan neck, the coil, and self-locating catheters. The latter are more expensive than Tenckhoff catheters but seem to offer some advantages, even if not sustained by adequate controlled trials so far. In addition, placement of these catheters may require different techniques or skills compared to the classical Tenckhoff. The most recent Italian guidelines based only on grade 1 and 2 evidence exclude that the type of catheter may influence the infection rate. There are no data from prospective controlled studies to evaluate the incidence of mechanical complications, hospitalization and technique survival. With regard to dialysis systems, it is still unclear if new plastic materials may offer any advantage over PVC. There is grade 1 evidence that Y-set and double-bag systems reduce the peritonitis rate compared to standard 1-way systems. The available data do not indicate significant differences in the incidence of peritonitis using Y-set compared with double-bag systems. The higher cost of double-bag systems is counteracted by shorter and easier training and by better acceptance by the patients.

[Antimicrobial agents for preventing peritonitis in peritoneal dialysis: guideline from the Italian Society of Nephrology]. / Strategie antimicrobiche per la prevenzione delle peritoniti in dialisi peritoneale: Linea Guida.

BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. The present guideline reports evidence of the use of antimicrobial agents for preventing peritonitis in peritoneal dialysis (PD). METHODS: SR of RCT and RCT on treatments aiming at preventing peritoneal dialysis peritonitis were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: One SR and 19 RCT were found addressing this issue. Staphylococcus Aureus nasal carriage treatment with mupirocin reduces exit-site and tunnel infections but not peritonitis. Topical gentamicin treatment on the exit site reduces Staphylococcus Aureus infection and peritonitis incidence. Intravenous antibiotics administration prior to catheter placement significantly reduces the risk of early peritonitis but not exit-site and tunnel infections. Oral nistatin associated with antibiotic treatment significantly reduces the incidence of Candida peritonitis. No other prophylaxis measure seems to be effective based on available evidence. CONCLUSION: In patients on peritoneal dialysis current evidence supports the hypothesis that topical mupirocin reduces the risk of Staphylococcus Aureus peritonitis, intravenous antibiotics prior to catheter placement prevent the risk of early peritonitis, and oral nistatin reduces the risk of Candida peritonitis. Further studies are necessary to test the effectiveness of other interventions.

[Catheter-related interventions to prevent peritonitis in peritoneal dialysis: guideline from the Italian Society of Nephrology]. / Strategie correlate al catetere per la prevenzione delle peritoniti in dialisi peritoneale: Linea Guida.

BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. The present guideline report evidence of catheter-related interventions to prevent peritonitis in peritoneal dialysis (PD). METHODS: SR of RCT and RCT of catheter-related interventions to prevent peritonitis in PD were identified referring to a Cochrane Library and Renal Health Library search (2005 update). RESULTS: Two SR and 17 RCT were found addressing this issue. Methodological quality of available RCT was suboptimal according to current methodological standards. The use of the Y-set systems with disinfectant and the twin-bag systems was associated with a significantly lower risk of peritonitis. No other catheter-related interventions were found to be of proven efficacy in preventing the risk of peritonitis and exit-site/tunnel infection in PD patients. CONCLUSION: It is still unknown whether any particular PD catheter design or implantation technique are effective to prevent peritonitis in patients on peritoneal dialysis. Further studies are necessary to test the effectiveness of new interventions.

[Treating peritonitis in peritoneal dialysis: guideline from the Italian Society of Nephrology]. / Terapia iniziale della peritonite in dialisi peritoneale: Linea Guida.

BACKGROUND: The current 3rd edition of the Italian Society of Nephrology guidelines has been drawn up to summarize evidence of key intervention issues on the basis of systematic reviews (SR) of randomized trials (RCT) or RCT data only. The present guideline reports evidence of interventions to treat peritonitis in peritoneal dialysis (PD). METHODS: SR of RCT and RCT on treatments for peritoneal dialysis peritonitis were identified referring to a Cochrane Library and Renal Health Library search (2005 update). Quality of SR and RCT was assessed according to current methodological standards. RESULTS: Thirty-six RCT were found addressing the intervention issue. Vancomycin or first generation cephalosporins may be used for treating peritoneal dialysis peritonitis due to Gram-positive agents. Third-generation cephalosporins or amino-glycosides may be used for Gram-negative agents peritonitis. Association of first-generation cephalosporins and agents against Gram-negative bacteria via the intraperitoneal route represents the most frequently used approach. Intraperitoneal administration of antibiotic agents is the most effective treatment of peritoneal dialysis peritonitis. Intermittent administration may be preferred to continuous administration of antibiotic agents in peritoneal dialysis peritonitis. CONCLUSION: In peritoneal dialysis peritonitis current evidence supports the hypothesis that intraperitoneal administration of antibiotics agents and intermittent administration may be preferred to other routes of administration and continuous administration. Further studies are necessary to test this hypothesis in selected patient populations.

Gamma glutamyltranspeptidase activity and viral hepatitis in dialysis population.

BACKGROUND: Numerous investigations have reported that viral hepatitis is associated with significant hepatocellular damage, as expressed by raised aminotransferases in serum, in dialysis population. However, scarce information exists on the activity of gamma glutamyltranspeptidase (GGTP) in dialysis patients with infection by hepatotropic viruses. OBJECTIVES: We measured serum GGTP values in a large cohort (n=757) of patients receiving long-term dialysis; healthy controls were also included. The relationship between GGTP values and a series of demographic, clinical, and biochemical parameters was analyzed. METHODS: Serum GGTP levels were tested by spectrophotometry. A subset (n=333) of dialysis patients was tested by molecular technology (branched-chain DNA (bDNA) assay) to evaluate the relationship between serum GGTP and HCV viremia. A subgroup (n=78) of dialysis patients was analyzed by an ultrasound scan of gallbladder and biliary tract to assess the presence of gallstone disease. Multivariate analyses were made using regression models; serum GGTP values were included as a dependent variable. The usefulness of serum GGTP levels in detecting HBsAg and anti-HCV positivity was evaluated using receiver operating characteristics (ROC) curve analysis. RESULTS: Univariate analysis showed that serum GGTP levels were significantly higher in HBsAg positive and/or anti-HCV positive patients than in HBsAg negative/anti-HCV negative patients on dialysis; 85.1+/-184.1 versus 25.86+/-23.9 IU/l (P=0.0001). The frequency of raised GGTP levels was 22.2% (41/184) among dialysis patients with chronic viral hepatitis. Multivariate analysis showed a significant and independent association between serum GGTP values and positive HBsAg (P=0.005) and anti-HCV antibody (P=0.0001) status. Mean GGTP values were significantly higher in study patients than controls, 32.32+/-60.02 versus 23.5+/-16.92 IU/L (P=0.01); however, no significant difference with regard to GGTP between study and healthy cohorts persisted after correction for age, gender, race, and viral markers. No relationship between gallstone disease and serum GGTP was found (NS). An independent and significant association (P=0.0291) between raised GGTP levels and detectable HCV RNA in serum was noted among patients tested by biology molecular techniques. ROC technology demonstrated that GGTP was equally useful for detecting HBV (P=0.0004) and HCV (P=0.0005) among dialysis patients. CONCLUSIONS: We found an independent and significant association between serum GGTP values and HBsAg and/or anti-HCV antibody in dialysis population. Twenty-two percent of dialysis patients with chronic viral hepatitis had elevated GGTP. No difference in GGTP between HBsAg- negative/anti-HCV- negative dialysis patients and healthy individuals was found. Routine testing for serum GGTP levels to assess liver disease induced by hepatotropic viruses or other agents in dialysis population is suggested.

Patient re-training in peritoneal dialysis: why and when it is needed.

The aim of this multicenter, quantitative, observational study was to analyze compliance and re-training needs of patients on peritoneal dialysis (PD) through the assessment of patient knowledge (with a Patient Questionnaire; phase 1) and patient behavior (home visit with a Score Card; phase 2). A total of 353 patients from 11 Italian centers participated in the first phase and 191 patients from nine centers in the second phase. Overall, 66% of questions on the Patient Questionnaire were answered correctly. Correct answers were more frequent in females than males, in patients under 55 years of age, and in those with higher education. The lowest rate of correct answers involved questions related to diet and physical activity (67% and 51%, respectively). Data collected during the home visit showed that 25% of patients were partially compliant with their drug therapy. Twenty-three percent of patients were non-compliant with the exchange protocol procedures, with a significant association between compliance and the incidence of peritonitis, and 11% were non-compliant with the exit-site protocol procedures without a statistically significant correlation to peritonitis. By combining the two evaluations, we found that approximately one-third (29%) of patients needed reinforcement of knowledge and ability to correctly perform PD as related to infection control and 27% for the correct use of drugs. Looking at the combined evaluation of infection control and drug use, results showed that 47% of patients needed re-training. This need for re-training was greater for younger patients (less than 55 years old), patients with lower education degree and patients in the early or late phase of PD therapy (less than 18 months or more than 36 months). Gender and degree of autonomy had no effect on the need for re-training.

Dialysis and kidney transplantation: similarities and differences in the psychological aspects of noncompliance.

BACKGROUND: Dialysis and kidney transplantation represent two effective strategies in treating chronic uremia, albeit with different results. Our study compared the psychological aspects of two categories of patients: patients who faced kidney transplantation and have been on dialysis, and noncompliant patients treated with these therapies. MATERIALS AND METHODS: On 170 patients (120 hemodialysis and 50 peritoneal dialysis) we used a personality analysis (MMPI2) and the COPE, which assessed the ability of patients to cope under certain conditions that can be perceived as stressful or, in any case, unusual. The screening succeeded in 11 cases among the first group and 9 in the second. Three of the 20 patients were considered to be partially noncompliant: 1 on peritoneal and the other 2 on hemodialysis. We also tested a control group of 300 people of different ages, sexes, social and cultural status, dates and kinds of transplantation (cadaveric or living donors). Of the 36 feedbacks received, only 30 were considered valuable. RESULTS: The results of the research showed that patients with less than 2 years of dialysis treatment and patients with more than 2 years survival after transplantation time were inclined to deny their disease and the possible emotions about their clinical status, drawing an inadequate attention to the difficulties. This behavior was clearer among noncompliant patients. Family problems and couple malaise in everyday life can push more and more of these patients to be noncompliant with therapeutic prescriptions, as they do not feel adequate support. The result is an excessive foreboding, poor disposition, and nervousness. CONCLUSIONS: Screening of patients' social and psychological status is useful as is psychological intervention for those who miss emotional support from the family. This psychological support is advisable for uremics who have to enter a waiting list and for those who are subject to postoperative treatment in order to promote compliant behavior.

De novo HCV infection among dialysis patients: a prospective study by HCV core antigen ELISA assay.

BACKGROUND: Dialysis patients remain a high-risk group for hepatitis C virus infection. The current diagnosis of hepatitis C virus in dialysis patients includes serological measurement of anti-hepatitis C virus antibody; however, nucleic acid amplification technology for assessing hepatitis C virus viraemia is commonly used in other populations. An enzyme-linked immunosorbent assay test for detecting antibody to hepatitis C nucleocapsid core antigen (hepatitis C virus core antigen) in human serum has been recently developed (hepatitis C virus Core Antigen enzyme-linked immunosorbent assay test). It is conceived for screening of donor blood products to significantly reduce the 'serologic window' occurring before seroconversion during acute hepatitis C virus. AIM AND METHODS: A cohort (n = 72) of patients on maintenance haemodialysis in a single unit in the years 2000-2003 was included. Study patients were tested monthly by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay in a prospective, clinical trial. Routine results obtained by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay test were confirmed by assessing hepatitis C virus viraemia by branched-chain DNA (bDNA) signal amplification assay. RESULTS: De novo hepatitis C virus infection was identified in three patients during the study period; the hepatitis C virus incidence was 1.38% (95% confidence intervals, 1.31-4.09) per year. In each patient, hepatitis C virus core antigen testing allowed the serological identification of acute hepatitis C virus before anti-hepatitis C virus seroconversion. Hepatitis C virus RNA testing confirmed the results obtained by hepatitis C virus Core Antigen enzyme-linked immunosorbent assay in all cases. The time from initial hepatitis C virus detection by hepatitis C virus Core Antigen Assay and anti-hepatitis C virus seroconversion was not greater than four weeks. Two (67%) of three patients with de novo hepatitis C virus acquisition were HBsAg negative; both these patients underwent an initial phase of hepatitis C virus viraemia that was associated with an increase in alanine aminotransferase activity and preceded the seroconversion to anti-hepatitis C virus antibody. Nosocomial transmission of hepatitis C virus between haemodialysis patients was implicated in at least two (67%) of these three patients. CONCLUSIONS: Serological testing for hepatitis C virus core antigen can identify acute hepatitis C virus infection before anti-hepatitis C virus seroconversion. The time from initial hepatitis C virus detection by hepatitis C virus core antigen assay and anti-hepatitis C virus seroconversion was not >4 weeks. De novo acquisition of hepatitis C virus in haemodialysis was associated with a rise in alanine aminotransferase levels. Hepatitis C virus core antigen enzyme-linked immunosorbent assay test results can be obtained in routine laboratories without the need of special equipment or training. Hepatitis C virus core antigen testing among anti-hepatitis C virus negative patients on maintenance dialysis is suggested in order to early assess de novo hepatitis C virus within dialysis units.

[Exit-site infection in peritoneal dialysis]. / Le infezioni dell'exit-site in dialisi peritoneale.

Exit-site infection remains one of the major peritoneal dialysis (PD) complications. The evolution of this infection can be secondary peritonitis and or peritoneal catheter loss. In this paper, the natural history of exit-site infection is described. In addition, the possible preventive measures are reviewed and analyzed. In particular surgical technique, perioperative protocols and the care of the exit-site are examined. Particular attention was devoted to the clinical role of staphylococcus (S.) nasal carriers and to the possible prevention of Staphylococcus Aureus infections in these patients. When infection occurs, different diagnostic tools could be appropriate, based on the amount of damage, the clinical symptoms and the medical history. Medical therapy should be selected based on international guidelines and prompt and timely intervention can be the cornerstone of successful therapy. In the case of infections resistant to local and parenteral antibiotic administration, the catheter should be removed. However, good results have been reported by removing part of the catheter and outer cuff; therefore, avoiding hemodialysis (HD) and reducing hospitalization and the need for surgery. When the peritoneal catheter requires removal, the possibility of removing and replacing the peritoneal catheter in a single operation requires consideration, to improve the quality of life and reduce the distress of the patient.

[HCV-related liver disease in hemodialysis population: clinical and biochemical characteristic]. / Epatopatia HCV-correlata in emodialisi: manifestazioni biochimiche e cliniche.

Hepatitis C virus (HCV) infection remains frequent among patients on maintenance dialysis. It has been claimed that infrequent and slight abnormalities in serum aminotransferase activity could occur in dialysis patients with HCV. We describe a 61-year-old male patient on maintenance dialysis who acquired HCV by a nosocomial route. The natural history of HCV in this patient over 8 yrs featured frequent and high increases in serum aminotransferase and gamma-glutamyl transpeptidase (gamma-GT) levels. In December 2001, serum GOT and GPT were, respectively, 965 and 1294 UI/L; gamma-GT activity was 241 UI/L. HCV genotype was 2a/2c; median HCV RNA values in serum were 2.3 x 105 UI/mL (range, 1.14 x 104 to 4.6 x 105 UI/mL). Total bilirubin, serum albumin, and colinesterase levels remained normal over the entire follow-up. Liver biopsy was not performed and interferon (IFN) therapy was not given. Currently, biochemical liver tests (GOT/GPT/gamma-GT) are in the upper range of normal values and the patient remains viremic. Efficacy and tolerability of initial monotherapy with IFN for chronic hepatitis C among dialysis patients are briefly discussed. Further studies are warranted to define the optimal anti-viral regimen for chronic hepatitis C in the dialysis population.

Effect of incremental doses of folate on homocysteine and metabolically related vitamin concentrations in nondiabetic patients on peritoneal dialysis.

The role of folate supplementation in reducing hyperhomocystinemia in patients on dialysis has been reported, but the optimal dose of folate is still unknown. The aim of the present study was to investigate whether greater than 5 mg/day folate supplementation provides any additional effect on plasma homocysteine (HCY) levels. The study was prospective, open, and had no control group. Of the 64 eligible nondiabetic patients on peritoneal dialysis with hyperhomocystinemia (>20 micromol/L), 56 were given oral folate (5 mg/day) for 3 months. When Hcy did not fall below 20 micromol/L, folate doses were increased by 5 mg every 3 months to up to 15 mg/day. With 5 mg/day supplementation, serum folate concentrations increased above the upper confidence limit in 23 patients and erythrocyte folate concentrations in 27 patients. Hcy levels decreased to less than 15 micromol/L in 6 cases and by more than 50% in 12 cases. Nineteen of the remaining patients were given 10 mg/day folate. After increasing the dose, serum and erythrocyte folate levels rose above the upper detection limit. In one patient, plasma Hcy concentrations decreased to less than 15 micromol/L. Ten patients were given 15 mg/day oral folate for an additional 3 months with no effect on homocystinemia. This study confirms that oral folate supplementation may improve hyperhomocystinemia even in patients on dialysis with normal serum or erythrocyte folate concentrations. In fact, serum and erythrocyte levels cannot predict the effect of supplementation on plasma Hcy levels. However, 5 mg/day folate supplementation normalized Hcy in 10% of cases and reduced Hcy levels in another 21%. Increasing the folate dose to greater than 5 mg/day had a minimal (10 mg/day) or no (15 mg/day) additional effect on Hcy concentrations. Despite the minimal effect of increasing folate doses, given the low cost, the absence of side effects, and the high cardiovascular risk for patients on peritoneal dialysis, a careful attempt to increase the dose of oral folate up to 10 mg/day might be suggested.

[Hepatopathy and hepatitis B virus infection in dialysis patients: cross-sectional study]. / Epatopatia e infezione da virus dell'epatite B nei pazienti in dialisi: studio trasversale.

BACKGROUND: Control of spread of HBV infection in dialysis units in developed countries has been one of the major advances in managing end-stage renal disease (ESRD). Patients with chronic HBV, however, continue to enter the population pool of dialysis patients and transplant candidates. The clinical significance related to the presence of HBsAg in serum of dialysis patients has not been completely understood. AIM AND METHODS: We collected demographic, biochemical and virological data from a large (n=464) population of patients on maintenance dialysis. This was done to assess the influence of virological and host factors on hepatocellular damage, as shown by serum aminotransferase activity. RESULTS: The frequency of HBsAg positivity in our dialysis population was 8.2 % (38/464); the rate of HBsAg positive patients showing HBe antigen was 20.6% (7/34). Twenty-two (84.6%) of 26 HBsAg positive patients showed detectable HBV DNA in serum by Amplicor HBV MonitorTM Test. HBsAg positive patients had serum aminotransferase activity significantly higher than HBsAg negative individuals; GOT (AST) 25.1+/-29.9 vs. 16+/-21.5 UI/L (p=0.001), and GPT (ALT) 31.3+/-52.5 vs. 17.7+/-21.9 UIL (p=0.034). In the subset of HBsAg positive dialysis patients, those in the replicative phase HBeAg positive) had aminotransferase activity higher than HBeAg negative individuals, AST, 42.3+/-43.6 vs. 22.4+/-27.3 UI/L (p=0.097) and ALT, 49.41+/-54.7 vs. 29.17+/-55.76 UI/L (NS) respectively. We did a multivariate analysis by standard least square model on the entire patient group and we found independent and significant association between detectable HBsAg in serum and AST (p=0.0089)and ALT (p=0.0159) values. There was an independent and significant relationship between age and ALT (p=0.01). CONCLUSIONS: In our study group, HBsAg positive patients on dialysis had serum aminotransferase activity significantly higher than that measured in HBsAg negative individuals. However, mean transaminase levels in HBsAg positive patients on dialysis were below the upper limit of normal for the reference range of healthy controls. HBsAg positive dialysis patients with active viral replication showed the greatest liver damage. Studies are in progress to understand further HBV-related liver disease in dialysis population.

Folate supplementation in peritoneal dialysis patients with normal erythrocyte folate: effect on plasma homocysteine.

The possible role of folate supplementation in reducing hyperhomocysteinemia in dialysis patients has been reported in several recent papers. However, scant data are available for peritoneal dialysis patients; besides, none of these studies investigated either the role of intraerythrocyte folate concentration or the presence of side effects caused by folate administration. Sixty-six peritoneal dialysis patients with hyperhomocysteinemia (>15 micromol/l) and normal folate status (as assessed by erythrocyte folate level >600 nmol/l) were randomly allocated to receive either oral folate (5 mg/day) or no vitamin supplementation. After 2 months of therapy, patients were requested to answer a questionnaire investigating the occurrence of symptoms possibly related to folate supplementation. Twenty-nine treated patients and 30 untreated controls completed the study. In the treated patients, serum and erythrocyte folate increased significantly (p < 0.0001) (respectively from 10.6 +/- 4.9 to 237 +/- 231 nmol/l and from 1,201 +/- 297 to 2,881 +/- 294 nmol/l) to levels at the uppermost limit of detection by laboratory methods. Serum vitamin B(12) levels did not change. Plasma homocysteine levels decreased from 54 +/- 32 to 23 +/- 14 micromol/l after folate supplementation and remained unchanged in the control group. After 4 months of folate therapy, homocysteine concentration was within the normal range in 5 patients (17%) and below 30 micromol/l in the other 21 (72%). Folate therapy resulted in a decrease in homocysteine of more than 50% in 45% of the patients and decrease of more than 20% in a further 38%. No significant symptoms were reported. Thus, serum and erythrocyte folate increase confirms that normal folate levels are inadequate in dialysis patients, even if serum and erythrocyte levels before folate supplementation cannot predict the effect on homocysteine plasma levels.