Association Between the Polymorphism of Angiotensin-Converting Enzyme Gene and Interleukin-1 Beta Gene and the Response to Erythropoietin Therapy in Dialysis Patients with Anemia.

Introduction: The polymorphism of the angiotensin-converting enzyme (ACE) gene and interleukin-1 beta (IL-1b) gene could be associated with resistance in the treatment of anemia in dialysis patients with recombinant human erythropoietin (rHuEPO). The aim of the study was to evaluate the association between the polymorphism of the ACE and IL-1b genes and the response to rHuEPO therapy in dialysis patients with anemia. Material and methods: The study investigated 69 patients on dialysis with anemia treated with recombinant human erythropoietin for 12 months. Genotyping of ACE and IL-1b polymorphism was done in all study patients at the initiation of the study. The patient's demographic characteristics, dialysis vintage, and laboratory parameters were also evaluated as factors associated with rHuEPO resistance. The erythropoietin resistance index (ERI) was calculated as the weekly rHuEPO dose per kg of body weight, divided by the hemoglobin (Hb) concentration in g/dl. Results: The Hb ≥ 110 g/l was registered in 37 (53.6%) patients. Patients with Hb ≥ 110 g/l were characterized by significantly higher serum levels of albumin, cholesterol, and iron than those with Hb < 110 g/l. The serum level of the CRP, the weekly dose of rHuEPO, and ERI were significantly higher in patients with Hb < 110 g/l compared to patients with Hb ≥ 110 g/l. The ERI value of ≥ 10 IUkg/weekly/g/dl was present in 27 (39.1%) patients. The serum levels of ferritin and CRP, and weekly dose of rHuEPO were significantly higher in patients with ERI value ≥ 10 IU kg/weekly/g/dl compared with the patients with ERI value < 10 IUkg/weekly/g/dl. There was no significant association between the ERI and polymorphism of the ACE and IL-1b genes in study patients. Conclusion: The polymorphism of the ACE and IL-1b genes was not significantly associated with the response to erythropoietin therapy in dialysis patients with anemia. Iron deficiency, malnutrition, and inflammation were factors associated with anemia and resistance to erythropoietin therapy in dialysis patients.

Ultrasound predictors of compensated liver cirrhosis in hemodialysis patients with hepatitis C.

Ultrasound examination was performed in 80 hemodialysis (HD) patients with chronic hepatitis C in order to determine the ultrasound predictors of compensated liver cirrhosis. The ultrasound score (US) was calculated from the morphological parameters (liver size, morphology, surface, echogenicity and spleen volume) and the hemodynamic parameters (portal vein diameter and portal vein mean flow velocity). The US ranged from 0 to 200, with a cut-off value of 66, for discrimination between absence and presence of liver cirrhosis. A logistic regression model with stepwise variable selection was used to determine predictors of the progression of liver disease. According to the calculated US, patients were divided into two groups. The first group consisted of 37 (46.3%) patients with US greater than 66, indicating the presence of compensated liver cirrhosis. The second group included 43 (53.7%) patients without liver cirrhosis, with US equal to or less than 66. The value of liver morphology was significantly higher, but the portal vein flow velocity was significantly lower in patients with compensated liver cirrhosis compared with those without cirrhosis. Furthermore, rounded liver surfaces and increased liver echogenicity were significantly more frequent in patients with compensated liver cirrhosis compared with the non-compensated group. Logistic regression model with stepwise discriminant analysis identified liver morphology, liver echogenicity and portal vein mean flow velocity as independent ultrasound predictors of compensated liver cirrhosis in HD patients with chronic hepatitis C. Ultrasound examination could be used for non-invasive diagnosis of compensated liver cirrhosis, with accurate estimation of the disease severity in HD patients with chronic hepatitis C.

Could living unrelated renal transplantation ameliorate the actual shortage of organs in the Balkan region?

BACKGROUND: Despite the efforts for more transplants performed with organs from deceased donors, the living renal transplantation is still the predominant transplant activity in the Balkan region. In order to adress the severe organ shortage, we started accepting unrelated (emotionally related) living donors (LURD). Here we present our 10-year experience with living unrelated renal transplantation (LURT). METHODS: Twenty four LURT were performed in our center in the last 10 years. The mean recipients and donors age was 41.7 and 47.2 years, respectively. As LURD spouses (n=17) and extended family members (n=7) were accepted predominantly. All donors went through careful psychological evaluation in order to confirm emotional relationship. The final decision was taken after both the recipient and the donor signed a consent in front of a judge. A quadruple sequential immunosuppressive protocol was used in all recipients. The 5-year Kaplan Meier graft survival rate, HLA mismatch, rejection episodes, delayed graft function, serum creatinine and Glomerular filtration rate-Modification of the diet in renal disease (GFR-MDRD) were analyzed. The results were compared with 30 living related renal transplants (LRT) performed during the same time with mean recipients and donors age of 35.9 and 58.5 years, respectively. RESULTS: The mean follow up for LURT and LRT recipients were 81.4 and 79.6 months, respectively. There was a significant difference regarding recipients and donors age, HLA mismatch (5.07 and 2.9) and rejection episodes (16% vs. 11%) in LURT and LRT recipients. The 5 years graft survival rate was excellent in both groups (83 and 81%, respectively). There was no significant difference in 5 years serum creatinine (129.3 vs 121.1 µmol/lit) and 5 years GFR-MDRD (56.6 and 58.6 ml/min). CONCLUSION: The authors present an excellent 5-year graft survival rate in both LURT and LRT recipients. Therefore, LURT could ameliorate the severe organ shortage in the region and could be recommended as a valuable source of organs in the countries with developed and underdeveloped deceased donor donation.

New approaches in the therapy of hepatitis C in dialysis patients.

Patients with renal disease are at increased risk of acquiring hepatitis C virus (HCV) infection because of their frequent exposure to blood from transfusions or exposure to HCV-contaminated medical equipment during hemodialysis. The prevalence of anti-HCV antibodies among hemodialysis patients varies between 5-10% in the developed world, and 10-70% in developing countries. Acute hepatitis C is often mild and associated with few, if any symptoms. The major complication of acute HCV infection is chronic hepatitis, which occurs in up to 80% of the cases, the long-term outcome being cirrhosis, portal hypertension, hepatic failure, and hepatocellular carcinoma. Interferon alpha (IFN-alpha) has shown activity against HCV. Twenty four to 48 week course of therapy with interferon could lead to a sustained loss of HCV RNA, normalization of alanine aminotrasferase (ALT) levels, and resolution of the liver disease. Sustained viral response was achieved in approximately half of the treated patients. Therapy with interferon was associated with a number of adverse events such as: "flu-like" symptoms, neurological, gastrointestinal symptoms, anemia, fatigue, thrombocytopenia, leucopenia. A major advance in therapy came with the addition of ribavirin to interferon therapy. Peginterferon-alpha-2a (40KD) is a new 'pegylated' subcutaneous formulation of interferon-alpha-2a, that was developed to improve the pharmacokinetic profile and therapeutic efficacy of interferon-alpha-2a. In our study, fourteen hemodialysis patients with chronic hepatitis C received 135 microg PEG-IFN alpha-2a subcutaneously, once a week, after dialysis session for a period of 48 weeks. In the intention-to-treat analysis, sustained viral response was present in 36% of the patients (five out of fourteen patients) at the end of the follow up period. The biochemical response with normalization of serum ALT levels during the treatment was observed in all treated patients (83 +/- 20.1 U/L at base line vs. 23.4 +/- 4.6 U/L after the 48 weeks; p < 0.01). At present, therapy for hepatitis C should be considered in hemodialysis patients with significant liver disease, minimal other co morbidities, and a reasonable likelihood of prolonged survival or if renal transplantation is planned.

Factors associated with various arterial calcifications in haemodialysis patients.

BACKGROUND: Haemodialysis (HD) patients are at increased risk of the development of arterial intimal (AIC) and medial calcification (AMC). The aim of our study was to analyze the association between the pre-defined potential risk factors and the status of various arterial calcifications in our HD patients. METHODS: In a cross-sectional study of 150 patients (91 male, mean age 54.55 +/- 12.46 yrs, HD duration 104.77 +/- 68.02 mths) we first determined the presence of AIC and AMC using plain radiography of the pelvis. We then compared the percentages of different radiogram findings in patients stratified according to various cut-off levels or the codes of each clinical and biochemical parameter (mean value of one year laboratory data recorded in the files). RESULTS: We determined arterial calcifications in 77.3% of our patients (AIC in 45.3%, AMC in 32%). The significantly higher frequencies of arterial calcifications of both groups (AIC and/or AMC) and isolated AIC presence were found in patients older than 55 at inclusion and 45 at the start of treatment with HD, with a serum C-reactive protein (CRP) > 4.5 mg/L, predominantly of male gender with diabetes. The patients with a significantly higher occurrence of arterial calcifications had lower percentages of total serum calcium (Ca) levels but within the K/DOQI guideline recommendations. Also, we found a significantly higher proportion of isolated AIC presence in the group of patients with corrected total serum Ca levels > 2.35 mmol/L and serum intact parathyroid hormone (iPTH) levels out of the range proposed by K/DOQI guidelines. In parallel, a significantly higher percentage of absence of arterial calcifications (ACA) was obtained in the patients with corrected total serum Ca levels < 2.35 mmol/L, body mass index (BMI) < 23 kg/m(2), mean pulse pressure < 60 mmHg, blood leucocytes < 6.5 x 10(9)L and serum triglycerides < 1.8 mmol/L. Finally, we found a significantly higher presence of isolated AMC in patients with mean Kt/V < 1.3 (poor dialysis adequacy), serum triglycerides > 1.8 mmol/L and outside K/DOQI guideline achievements for corrected total serum Ca. In the 12 month period data analyzed, there were no significant differences in other risk factors such as the dose of prescribed calcium carbonate and vitamin D3, serum levels of albumin, cholesterol, phosphate (P) and Ca x P product. CONCLUSIONS: AIC and AMC were frequently present in our HD population. Age, gender, BMI, diabetes, pulse pressure, dialysis adequacy, serum CRP, triglycerides, Ca and iPTH, as well as blood leucocyte levels were associated with the occurrence of arterial calcifications in our HD patients.

Patterns of viraemia in haemodialysis patients with hepatitis C.

Clinical features, aminotransferases levels, and antibody to HCV have only limited correlation with the activity of liver disease and cannot accurately predict persistence versus eradication of the virus in haemodialysis patients. Although permanent loss of serum HCV RNA appears to correlate with resolution of the disease, little is known about the predictive value of a single HCV RNA value. The aim of the study was to evaluate the viraemia in the serum of HCV antibody positive haemodialysis patients during a period of 3 years. The study group consisted of 65 HCV antibody positive patients from our dialysis unit. HCV antibodies were measured every 6 months by ELISA third-generation assay. The presence of serum HCV RNA was assessed by reverse-transcriptase polymerase chain reaction (RT-PCR) once a year during the period of 3 years. Serum levels of aminotransferases were measured monthly with standard automated analyzers. There were three different patterns of viraemia after the third assessment of the serum HCV RNA in HCV antibody positive patients: 47% (30/65) were persistently HCV RNA positive, 38% (25/65) were intermittently HCV RNA positive, and 15% (10/65) were persistently HCV RNA negative. The dominant genotype was 1a, detected in 97% of the patients positive for HCV RNA. The HCV RNA persistently positive patients had significantly higher levels of ALT compared to HCV RNA persistently negative patients (50.07 +/- 30.0 vs. 28.5 +/- 10.0 U/L, p < 0.027). There was no significant difference between the three groups of patients according to age, haemodialysis duration, and serum levels of AST. This pattern of intermittent viraemia clearly showed that a single negative result of the presence of serum HCV RNA in an HCV antibody positive patient should not be taken as a proof of a persistent resolution of HCV. Thus, repeated testing for HCV RNA is necessary to assess viraemia accurately in HCV antibody positive patients. HCV antibody positive patients who were persistently serum HCV RNA negative could be potentially infectious because of the possibility of the persistence of occult hepatitis C.