The use of intradialytic parenteral nutrition in acutely ill haemodialysed patients.

BACKGROUND: Protein/caloric malnutrition is a problem in chronically haemodialysed patients, and is an independent risk factor for increased mortality in these patients. OBJECTIVES: To assess the safety and efficiency of intradialytic parenteral nutritional (IDPN) as nutritional support in acutely ill haemodialysis patients. METHODS: Twenty-two haemodialysis patients received IDPN after either major surgical or medical illnesses. Parameters measured included possible complications of IDPN, dialysis adequacy, patients' weight, protein catabolic rate (PCR) and serum levels of albumin, pre-albumin, creatinine, cholesterol, c-reactive protein (c-RP) and haemoglobin. After the end of the study all patients were followed-up for a further 6 months. RESULTS: Patients received IDPN for 1.5-48 months. Eighteen patients received IDPN <6 months. IDPN was safe for all patients. Throughout this period dialysis remained adequate. Weight loss in all patients ceased after approximately 2 months of IDPN. PRC, serum albumin, pre-albumin, cholesterol and creatinine levels all increased significantly. c-RP dropped from 77+/-86 mg/l to 9+/-10 mg/l. CONCLUSIONS: IDPN can be safely used in haemodialysed patients who are acutely ill and are unable to meet daily nutritional requirements with an oral intake. All studied parameters of nutrition and inflammation improved significantly while patients were treated with IDPN.

Non-occlusive mesenteric ischemia in chronically dialyzed patients: a disease with multiple risk factors.

BACKGROUND: Non-occlusive mesenteric ischemia (NOMI) can be a fatal complication in dialysis patients. Intradialytic hypotension is usually the precipitating factor. The occurrence of 16 cases in 5 years (1998-2002), compared with only 4 in previous years, led us to investigate other risk factors contributing to NOMI. A control group of stable hemodialysis patients was used for comparison. RESULTS: 20 patients were studied: 17 diagnosed surgically, and 3 clinically. The mean age was 70.8 +/- 1.8 years, and the male:female ratio 7:13. Nineteen patients were on hemodialysis. Clinically overt atherosclerosis was present in 17 patients. Preceding dialysis-associated hypotension was identified in all patients studied and access thrombosis in 6 patients. In all patients, abdominal pain was the presenting symptom. Initial abdominal examination was unimpressive in 16 patients. The hemoconcentration, leukocytosis and metabolic acidosis were the most prominent laboratory findings. 5/11 abdominal sonograms showed intestinal pathology. 2/3 angiographies were diagnostic. Three patients responded to early fluid challenge and did not require surgery. Pathology was related to the area of the superior mesenteric artery in all 15 patients operated. Twelve (60%) patients died from the event. The 1-year mortality rate was 17/20 patients (85%). Possible contributing factors, other than dialysis-associated hypotension, included: high-dose recombinant human erythropoietin (rhEPO) therapy (179 +/- 35 vs. 116 +/- 10 U/kg/week in the control group, p < 0.05); metastatic calcifications (abdominal aorta 14/14, aortic valve 11/18; medial calcification of mesenteric arteries in 2/11 pathology specimens); digoxin, and hypoalbuminemia. CONCLUSIONS: The increased incidence of NOMI in dialysis patients may be related to overly aggressive rhEPO therapy and the unsuspected presence of mesenteric arterial medial calcifications. Identification of patients at risk, prevention of intradialytic hypotension and a controlled increase in dry weight may help to reduce the incidence of NOMI in chronically dialyzed patients.

Improved immunogenicity of a novel third-generation recombinant hepatitis B vaccine in patients with end-stage renal disease.

Hepatitis B (HBV) infection remains a significant epidemiological problem in the end-stage renal disease (ESRD) population. Vaccination programs using second-generation vaccines lead to effective seroprotection in only 50-60% of these patients. The purpose of this case series was to describe our experience with a novel third-generation vaccine, Bio-Hep-B, in ESRD patients who had not developed protective anti-HBs titers following a second-generation HBV vaccination protocol. Twenty-nine ESRD patients who had not responded in the past to a standard second-generation HBV vaccination protocol were included in this series. Each patient received 10 microg of Bio-Hep-B) intramuscularly at 0, 1 and 6 months. A month after completion of the vaccination protocol, anti-HBs antibody levels were measured. Following immunization, 25 of 29 patients (86%) developed seroprotective anti-HBs levels > or =10 mIU/ml. There was a significant difference in the titers of anti-HBs antibodies prior to and following vaccination (p < 0.0001). Statistical analysis of the variables age, gender, diagnosis, dialysis mode, weight, hemoglobin, albumin, and KT/V failed to detect predictors of antibody response. A retrospective analysis of the results of a second-generation vaccination program for the years 1999-2001 in our department showed that 19 of 36 (56.4%) ESRD patients developed seroprotection. In conclusion, the results of this study show that the third-generation HBV vaccine Bio-Hep-B is highly immunogenic in the population of ESRD patients who did not respond in the past to a second-generation vaccine. This enhanced seroprotection offers hope that the new vaccine will reduce the rate of non-responders and help to eliminate HBV infection from dialysis centers.

Spontaneous DNA repair in human peripheral blood mononuclear cells.

DNA molecules are constantly damaged during mitosis and by oxygen-free radicals produced by either cellular metabolism or by external factors. Populations at risk include patients with cancer-prone disease, patients under enhanced oxidative stress, and those treated with immunosuppressive/cytotoxic therapy. The DNA repair process is crucial in maintaining the genomal DNA integrity. The aim of this study was to evaluate spontaneous DNA repair capacity of peripheral blood mononuclear cells (PBMC) from normal blood donors. PBMC DNA repair ability represents DNA repair by other tissues as well. It is shown in the present study that in vitro incorporation of [3H]thymidine in non-stimulated PBMC expresses the ability of the cells to repair DNA damage. This method was validated by double-stranded DNA measurements. Both catalase and Fe2+ increased DNA repair, the former by preventing re-breakage of newly repaired DNA and the latter by introducing additional DNA damage, which enhanced DNA repair. Better understanding of DNA repair processes will enable to minimize DNA damage induced by oxidative stress.

DNA repair in mononuclear cells: role of serine/threonine phosphatases.

Treatment with cyclosporin A (CsA) in kidney-transplant recipients is associated with reduced DNA repair and enhanced cancer incidence. CsA is an inhibitor of the serine/threonine phosphatase calcineurin, also termed PP2B, which is a Ca(2+)/calmodulin-dependent phosphatase. In this study we sought to elucidate the role of calcineurin in DNA repair using CsA and tacrolimus; examine whether UV-induced DNA repair is associated with dephosphorylation; and investigate whether phosphatases other than calcineurin are active in DNA repair, in light of the fact that calcineurin inhibition only partially suppressed DNA repair. Peripheral blood mononuclear cells from healthy donors were used. In vitro, we assayed UV-induced DNA repair by measuring the incorporation of tritiated thymidine in UV-irradiated cells. We gauged phosphatase activity indirectly by measuring free inorganic phosphate (Pi) excreted into the medium. The phosphatase assay was performed under the same conditions and in parallel to the DNA-repair assay. Tacrolimus, like CsA, inhibited DNA repair in a dose-dependent fashion. DNA repair was associated with production of Pi, which correlated with the number of cells performing DNA repair. Phosphatase activity increased after UV irradiation. DNA repair correlated directly with phosphatase activity, whereas CsA reduced both DNA repair and Pi production. Inhibition of calmodulin by trifluoperazine and W7 [N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide] reduced DNA repair in part. We investigated the role of the Ca(2+)-independent phosphatases PP1 and PP2A using specific inhibitors. Calyculin A, which inhibits both phosphatases, reduced DNA repair. Endothall, a PP2A inhibitor, had no effect on DNA repair. Okadaic acid, which is mostly a PP2A inhibitor but also a weak inhibitor of PP1, reduced DNA repair only slightly. We suggest that DNA repair is mediated by way of Ca(2+)-dependent and Ca(2+)-independent pathways, with calcineurin and PP1 being the respective phosphatases involved in each pathway.