A 3-year follow-up of HCV-RNA viraemia in haemodialysis patients

BACKGROUND: Hepatitis C virus (HCV) infection in a population of haemodialysed patients was studied over a 3-year follow-up period in order to evaluate the changes in viral RNA, diversity of genotypes, and serological response to synthetic HCV peptides. METHODS: Twenty-eight (32.9%) patients with anti-HCV antibodies from a total of 85 patients assigned to a haemodialysis unit were studied. The serological response to immunopeptides was evaluated by immunoblotting, viral RNA in serum was detected using the polymerase chain reaction (RT-PCR), and genotyping was carried out by hybridization with probes fixed to nitrocellulose paper. RESULTS: Of the 28 haemodialysis patients who had anti-HCV antibodies, three (10.7%) were always RNA negative, six (21.4%) were always RNA positive, and 19 (67.8%) were variable RNA. There was an incomplete antibody response to non structural antigens in non-viraemic patients. Genotype was determined in 23 patients, and the other two could not be genotyped. The most common genotype was 1b (69.4%), followed by 1a (17.4%), and 2a, 3a, and 4a (each 4.4%). CONCLUSIONS: Haemodialysis patients, when followed up for a long time, frequently show an intermittent HCV viraemia state, suggesting that HCV cannot be evaluated adequately by isolated RNA determinations.     

Silicon and aluminium interactions in haemodialysis patients

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.     

High-dose alfacalcidol improves anaemia in patients on haemodialysis

BACKGROUND: Alfacalcidol is efficient for treating secondary hyperparathyroidism in patients on maintenance haemodialysis (HD). Little is known about the direct impact of high-dose alfacalcidol on anaemia in end-stage renal failure. We therefore carried out a prospective study over 18 months to examine the direct effect of high-dose alfacalcidol on erythropoiesis in erythropoietin (rHuEpo)-dependent anaemic patients on HD for more than 6 months with moderate hyperparathyroidism. STUDY DESIGN: Twelve patients received oral alfacalcidol at a dosage of 6-7 micrograms per week and calcium carbonate during the first 12 months, calcium carbonate without alfacalcidol during the next 3 months, and again alfacalcidol and calcium carbonate during the last 3 months. Criteria for selection were haemoglobin < 10 g/dl, iPTH > 250 pg/ml, transferrin saturation (TS) > 25%, S-ferritin > 300 micrograms/l, and S-aluminium < 40 micrograms/l. RESULTS: Haemoglobin (Hb) and reticulocyte counts increased during the first phase, decreased and returned to a baseline prior to starting vitamin D treatment in the second phase, and again increased when alfacalcidol was reintroduced, whereas iPTH decreased during the first 3 months of the first phase and then remained stable, as did S-calcium, which increased during the first 3 months and then remained constant. S-phosphate increased during the first and third phases, and decreased during the second phase. Two patients during the first phase and one patient during the third phase presented hypercalcaemia; requiring a temporary discontinuation of alfacalcidol. CONCLUSION: High-dose alfacalcidol is efficient in anaemic patients with moderate hyperparathyroidism on maintenance HD and has a direct effect on erythropoietic cells regardless of serum calcium and iPTH levels.     

Diurnal blood-pressure variations in haemodialysis and CAPD patients

The influence of variations in fluid state on diurnal blood pressure was studied by measuring day-time and night-time blood pressure during a 3-day interdialytic period in 10 normotensive and 10 hypertensive haemodialysis patients using Spacelab 90207 Monitors. Ambulatory blood pressure was also measured during 24 h in 11 normotensive and nine hypertensive CAPD patients, and in nine normotensive and 11 hypertensive control patients with a normal renal function. Antihypertensive drugs had been discontinued for at least 3 weeks before the study period. Optimal dry weight in the haemodialysis patients was estimated by echography of the inferior vena cava and in the CAPD patients on clinical grounds. Although in the dialysis patients and controls a significant nocturnal blood pressure reduction was found, day-night blood pressure difference in the dialysis patients was blunted when compared with the control patients. No significant differences in diurnal blood pressure variation was found between the normotensive and the hypertensive patients. Day-night blood pressure differences in the haemodialysis patients did not change during the 3-day interdialytic period. Also the more stable fluid state of the CAPD patients was not associated with significant different diurnal blood pressure variation compared to the haemodialysis patients. We conclude that factors other than changes in extracellular fluid volume are responsible for a blunted day-night difference in blood pressure in dialysis patients.     

Correction of anaemia in haemodialysis patients with recombinant human erythropoietin

The binding and degradation of radiolabelled immune complexes by cultured rat glomerular mesangial cells were measured and compared with the binding and degradation by thioglycollate-elicited rat peritoneal macrophages. Mesangial cells are generally considered to be a modified pericyte with smooth muscle-like properties, but they were able to bind and degrade soluble immune complexes at rates comparable to those of the macrophages. In a second study, the ability of cultured mesangial cells to bind and degrade immune complexes of varying molecular weight was assessed. Very large, insoluble complexes were found to bind to mesangial cells more avidly than small soluble complexes, but unlike the small complexes, the large complexes did not appear to undergo degradation. These findings support a role for the intrinsic mesangial cell in the elimination of small soluble immune complexes as they arrive in the glomerulus. They also provide a possible explanation for the paradox that large immune complexes--i.e., electron-dense deposits--can persist in the mesangium next to the intrinsic mesangial cells without being rapidly destroyed.     

Hypertension in haemodialysis patients: is it only hypervolaemia?

CT and MR findings in two patients with hepatoerythropoietic porphyria are presented. CT scans showed atrophy and cortical mineralization at the same level. MR examination performed in one of the two patients showed mainly frontal cortical atrophy and punctate bright signal on T1- and T2-weighted sequences.     

Cardiac valve calcification in haemodialysis patients: role of calcium-phosphate metabolism

BACKGROUND: Cardiac valve calcification (VC) has been detected with increased frequency in haemodialysis (HD) patients, making it necessary to determine the potential pathogenic factors in uraemic patients. METHODS: A total of 92 chronic HD patients (39 female, 53 male) and 92 age and gender-matched nondialysis control subjects were evaluated by echocardiography and a severity score for VC was determined. Calcium phosphate metabolism was evaluated at the beginning of haemodialysis. RESULTS: We found a greater prevalence of VC in dialysis patients than in normal patients (mitral annulus 44.5% vs 10%, P = 0.02; aortic annulus 52% vs 4.3%, P = 0.01). HD patients with mitral calcification were found to be older than patients without calcification, were on long-term renal replacement therapy, had longer duration of predialysis arterial hypertension, had greater values of the highest value of mean calcium phosphate product in 6 successive months (CaxP) and the highest absolute value of calcium-phosphate product (CaxPmax). We also found a positive correlation between calcification score, age, and CaxP. No correlation was found between actual VC and arterial hypertension or parathyroid hormone. Multiple stepwise regression analysis selected age and CaxP as the most predictive parameters for mitral calcification (r = 0.47). Mitral calcification was associated more frequently with rhythm and cardiac conduction defects, valvular insufficiency and with peripheral vascular calcification. Aortic calcification was correlated with age (r = 0.42) and longer duration of predialysis arterial hypertension. CONCLUSION: Our study confirmed an increased prevalence of VC in HD patients and selected age and calcium phosphate product as the most predictive parameters. These findings support careful monitoring of calcium metabolism beginning at the early stages of end-stage renal failure to reduce the risk of heart disease.     

Disappearance of mitral and tricuspid regurgitation in haemodialysis patients after ultrafiltration

We recovered an unusual bacterial strain from blood or sputum of three patients with septicemia, endocarditis, and/or respiratory failure. The three isolates were thin, curved, gram-negative, light brown, pigment-producing bacilli with variable catalase activity. They were asaccharolytic, oxidase-negative, nonmotile, and fastidious. Identification was not possible on the basis of these characteristics alone or in combination with cellular fatty acid profiles. Nucleic acid amplification and sequence analysis of the 16S rRNA gene revealed that all three isolates were identical and most closely related to the emerging pathogen Bordetella holmesii, diverging from the published sequence at three nucleotide positions (99.8% similarity). Isolation of a B. holmesii-like pathogen from sputum suggests that, in addition to producing septicemia, the organism may inhabit the respiratory tract like other Bordetella species.     

Distribution of HCV genotypes in patients infected by different sources

During March and April 1993, a massive outbreak of Cryptosporidium infection resulted from contamination of the public water supply in Milwaukee, Wisconsin. The health impact of this outbreak in HIV-infected persons was unknown but was perceived as severe. We surveyed HIV-infected persons who resided in the greater Milwaukee area to examine the acute health impact of cryptosporidiosis on this population. Data from a random-digit dialing survey in the general population residing in the same area were used for comparison. The attack rate of watery diarrhea suggestive of cryptosporidiosis was lower in HIV-infected persons (32%) than in the general population (51%). There was no significant difference in attack rate in HIV-infected persons based on CD4+ T-lymphocyte count. In persons with watery diarrhea, HIV-infected persons were more likely to experience cough (42%), fever (52%), and dehydration (55%). In HIV-infected persons with watery diarrhea, persons with CD4+ T-lymphocyte counts <200/microl had longer duration of diarrhea and were more likely to seek medical attention and be hospitalized. During this massive waterborne outbreak, HIV-infected persons were not more likely to experience symptomatic Cryptosporidium infection than the general population. However, once infected, the duration and severity of illness was greater in HIV-infected persons, especially if the CD4+ T-lymphocyte count was <200/microl.     

Prevalence of JC virus viraemia in HIV-infected patients with or without neurological disorders: a prospective study

Superoxide dismutase (SOD) and catalase (CAT) activities were measured in blood from 420 individuals: control population 126, males and females, age between 50 to 93 years of age without any relevant pathology. Pathological population: 294 patients, males and females, age between 50 to 93 years of age, with some disease in the cardiovascular system and in the osteoarticular system, myoma, prostatic pathologies, Chronic Obstructive Pulmonary Disease (EPOC), and Acute Cerebral Vascular Accident (ACVA). The method of Minami and Yoshikawa (SOD) and the method of Aebi (CAT) were judged the techniques of choice for a population study. Statistical methods: ANOVA and Student's "t". 1) The results were that levels of activity for SOD and CAT were increased for women in control population, and 2) the level of activity for CAT decreases with aging. In the pathological population, we detected: 3) increased activity for SOD in cardiovascular diseases, myomas, EPOC and ACVA. 4) for CAT the level of activity decreases in cardiovascular and prostatic diseases, EPOC and ACVA. 5) while in osteoarticular diseases levels of activity for SOD and CAT were standard, but SOD level decreases with aging, for CAT in cardiovascular diseases and EPOC, too. Both enzymes work to balance the antioxidant system.     

Phagocyte-induced oxidative stress in patients with haemodialysis treatment and organ transplantation

This study was designed to investigate any seasonal (spring, summer, autumn and winter) changes in haematological parameters in the blood of Tinca tinca measuring the number of red blood cells (RBC), haematocrit, white blood cells, and total plasma proteins. The results show significant changes in RBC and haematocrit in males comparing spring and summer with autumn and winter, whereas in females the RBC remained constant for all 4 seasons but the haematocrit decreased in autumn and winter compared to spring and summer. The white blood cells of male and female animals were significantly lower in spring and winter compared to summer and autumn. In male fish total protein contents significantly decreased in autumn and winter compared to spring and summer, whereas in females protein output significantly decreased in winter compared to the other seasons. The results indicate marked seasonal variation in the blood of male and female Tinca tinca. This variation may play a important protective role for the survival of the animals.     

Desferrioxamine improves burst-forming unit-erythroid (BFU-E) proliferation in haemodialysis patients

Biotransformations with recombinant Escherichia coli expressing the genes encoding 2-nitrotoluene 2,3-dioxygenase (2NTDO) from Pseudomonas sp. strain JS42 demonstrated that 2NTDO catalyzes the dihydroxylation and/or monohydroxylation of a wide range of aromatic compounds. Extremely high nucleotide and deduced amino acid sequence identity exists between the components from 2NTDO and the corresponding components from 2,4-dinitrotoluene dioxygenase (2,4-DNTDO) from Burkholderia sp. strain DNT (formerly Pseudomonas sp. strain DNT). However, comparisons of the substrates oxidized by these dioxygenases show that they differ in substrate specificity, regiospecificity, and the enantiomeric composition of their oxidation products. Hybrid dioxygenases were constructed with the genes encoding 2NTDO and 2,4-DNTDO. Biotransformation experiments with these hybrid dioxygenases showed that the C-terminal region of the large subunit of the oxygenase component (ISP alpha) was responsible for the enzyme specificity differences observed between 2NTDO and 2,4-DNTDO. The small subunit of the terminal oxygenase component (ISP beta) was shown to play no role in determining the specificities of these dioxygenases.     

Interferon treatment for hepatitis C virus infection in patients on haemodialysis

BACKGROUND: This study examined the efficacy and tolerability of interferon alpha-2b (IFN) in the treatment of chronic hepatitis C virus (HCV) infection in patients on maintenance haemodialysis. METHODS: A 24-month prospective cohort study was performed in 11 HCV RNA-positive haemodialysis patients, who were treated with IFN at 3 MU thrice weekly for 6 months. Serial biochemical and virological monitors included serum alanine aminotransferase levels, and HCV RNA by both qualitative PCR assay and quantitative bDNA assay. HCV genotypes were determined by PCR and nucleotide sequencing. Ten patients had baseline liver biopsy. RESULTS: HCV genotypes 1b and 2b were identified in 10 and one patients respectively. Six (55%) patients had biochemical and/or histological features of chronic active hepatitis before treatment. All 11 patients became HCV RNA-negative by PCR, with normalization of deranged aminotransferase levels, within 2-8 weeks of IFN therapy. HCV RNA reappeared in eight (73%) patients 2-8 weeks after the cessation of IFN, while biochemical relapse occurred in six (55%) patients. Sustained eradication of HCV was achieved in three (27%) patients. Sustained responders were characterized by pretreatment HCV RNA level < 3.5 x 10(5) Eq/ml as determined by the bDNA assay, and less severe histological abnormalities ('Total score' 1.7 +/- 1.2 compared to 5.4 +/- 2.2 in relapsers, P < 0.05). HCV RNA levels were similar before and after IFN treatment in non-responders and relapsers. Persistent malaise and poor appetite were noted in eight (73%) patients during IFN therapy. Other side-effects of IFN included the exacerbation of anaemia, induction of resistance to erythropoietin, weight loss, and reduced serum albumin level. CONCLUSIONS: Eradication of chronic HCV infection with IFN can be achieved in 27% of haemodialysis patients. Predictors of sustained response include low baseline HCV RNA level and mild liver pathology. Virological relapse can occur despite normal liver biochemistry. Exacerbation of anaemia, erythropoietin resistance, and malnutrition constitute the side-effects of IFN that deserve special attention in uraemic subjects.