Drug interaction between sevelamer and cyclosporin.
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Biomedical subjects
Publications and source records attributed to Michel Jadoul.
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BACKGROUND: The high prevalence of anti-hepatitis C virus (HCV) antibodies in HD patients has been known since the early 1990s but its evolution over the last decade is poorly documented. METHODS: All chronic HD patients from 15 Belgian units were tested at (re)start of HD and every 18 months for anti-HCV antibodies (ELISA 2 in May 1991 and November 1992, then ELISA 3 until May 2000). All chronic HD patients from HD units from eight other European countries, whose prevalence of anti-HCV (+) patients had been studied in 1991-1994 (and published except in one country), were tested for anti-HCV antibodies in 1999. RESULTS: Anti-HCV (+) prevalence decreased (P<0.001) from 13.5 (1991) to 6.8% (2000) in the Belgian cohort (n = 1710). Prevalence also decreased (P<0.05) in the participating units from France (42-30%), Sweden (16-9%) and Italy (28-16%), tended to decrease in the participating units from UK (7-3%, P = 0.058) and Hungary (26-15%, P = 0.057) but did not change (NS) in the participating units from Germany (7 to 6%), Spain (5 to 12%) and Poland (42 to 44%). In the Belgian cohort, the prevalence of anti-HCV(+) at (re)start of HD did not change significantly over 1991-2000. CONCLUSION: The prevalence of anti-HCV(+) in HD has decreased markedly over the last decade in the participating units from most European countries. This decrease should reduce further the risk of nosocomial and occupational HCV infection in HD and ultimately contribute to improved long-term prognosis of HD patients and kidney graft recipients.
BACKGROUND: Darbepoetin alfa, a glycoprotein that stimulates erythropoiesis by the same mechanism as endogenous erythropoietin, has a 3-fold longer terminal half-life than recombinant human erythropoietin, allowing for an extended dosing interval. Darbepoetin alfa is currently recommended for once-weekly and once every 2 weeks administration in patients with chronic renal failure (CRF). The objective of this study was to explore once-monthly administration in this patient population. METHODS: Clinically stable dialysis patients (mean haemoglobin concentration, 10.0-13.0 g/dl) receiving stable darbepoetin alfa therapy administered once every 2 weeks in a long-term treatment study were converted to darbepoetin alfa once every 3 weeks for 20 weeks and then, if haemoglobin concentrations were successfully maintained between 10.0 and 13.0 g/dl, were converted to darbepoetin alfa once every 4 weeks for 20 weeks. The darbepoetin alfa dose was titrated to maintain haemoglobin within a target range (-1.0 to +1.5 g/dl of baseline haemoglobin, and between 10.0 and 13.0 g/dl). Success with the extended dosing interval was defined as maintenance of mean haemoglobin >/=10.0 g/dl during a 4-week evaluation at the end of the dosing period. RESULTS: Of the 54 patients who entered the study, 38 patients were converted to darbepoetin alfa administered once every 4 weeks. Of these, 36 patients were considered evaluable and 30 (83%) of those evaluable patients successfully maintained the target haemoglobin. For successful patients the mean (SD) haemoglobin during evaluation was 11.16 (0.60) g/dl, and the mean change in haemoglobin from baseline to evaluation was -0.26 g/dl (95% CI: -0.51, -0.01). The median change from baseline in average weekly darbepoetin alfa dose was 1.61 microg (95% CI: 0.00, 4.75). Adverse events were consistent with those expected for this patient population. CONCLUSIONS: Darbepoetin alfa, administered once monthly, maintained haemoglobin effectively and safely in most dialysis patients stabilized previously on once every 2 weeks dosing. Once-monthly dosing may optimize anaemia management for patients with CRF and for health care providers.
BACKGROUND: Hepatitis C virus (HCV) remains a problem within hemodialysis units. This study measures HCV prevalence and seroconversion rates across seven countries and investigates associations with facility-level practice patterns. METHODS: The study sample was from the Dialysis Outcomes and Practice Patterns Study (DOPPS), a prospective, observational study of adult hemodialysis patients randomly selected from 308 representative dialysis facilities in France, Germany, Italy, Japan, Spain, the United Kingdom, and the United States. Logistic regression was used to model odds of HCV prevalence, and Cox regression was used to model time from study entry to HCV seroconversion. RESULTS: Mean HCV facility prevalence was 13.5% and varied among countries from 2.6% to 22.9%. Increased HCV prevalence was associated with longer time on dialysis, male gender, black race, diabetes, hepatitis B (HBV) infection, prior renal transplant, and alcohol or substance abuse in the previous 12 months. Approximately half of the facilities (55.6%) had no seroconversions during the study period. HCV seroconversion was associated with longer time on dialysis, human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), HBV infection, and recurrent cellulitis or gangrene. An increase in highly trained staff was associated with lower HCV prevalence (OR = 0.93 per 10% increase, P= 0.003) and risk of seroconversion (RR = 0.92, P= 0.07). Seroconversion was associated with an increase in facility HCV prevalence (RR = 1.36, P < 0.0001), but not with isolation of HCV-infected patients (RR = 1.01, P= 0.99). CONCLUSION: There are differences in HCV prevalence and rate of seroconversion at the country and the hemodialysis facility level. The observed variation suggests opportunities for improved HCV outcomes.
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The objective of this paper is to document the prevalence of indicators of acute renal injury in a series of methanol-poisoned patients treated in an intensive care unit and to discuss the possible mechanisms. This is a retrospective analysis of the medical records of 25 consecutive patients admitted to the intensive care unit after severe intentional methanol poisoning. Acute renal impairment was defined as a serum creatinine concentration higher than 177 micro mol/L and/or a urinary output on admission and for the first 24 h below 0.5 ml/kg/h. Clinical pathological signs of acute renal injury were found in 15 patients. In comparison with the 10 other patients taken as control group, the patients who developed renal injury had a lower blood pH value on admission, a higher serum osmolality, and a higher peak formate concentration. Two factors contributing to renal injury could be identified: hemolysis and myoglobinuria. The role of osmotic changes (osmotic nephrosis) or of a direct cytotoxic effect of formic acid remains speculative. Analysis of proteinuria suggests that proximal tubular cells may be preferentially affected. Results of histopathological evaluation of the kidney on a limited sample size (n = 5) were inconclusive but suggestive of possible hydropic changes in the proximal tubule secondary to methanol toxicity. Acute renal injury may be associated with other signs of severity in methanol poisoning, but it is almost always reversible in survivors. Indicators of acute renal injury were identified. The pathophysiology of this acute renal injury is multifactorial and far more complex than shock-related tubular necrosis.
Increased leakage of surfactant proteins A and B (SP-A and SP-B) and Clara cell secretory protein (CC16) from the air spaces into the circulation occurs in a range of respiratory conditions. However, circulating levels depend not only on the rate of entry into the circulation, but also on the rate of clearance. In order to clarify the role of the kidney in the clearance of these proteins, serum levels were related to markers of glomerular filtration in 54 non-smoking patients with varying degrees of renal dysfunction, none of whom had respiratory disease or were receiving dialysis at the time of sampling. Serum SP-A was related to SP-B (r = 0.53, p < 0.001) and to CC16 (r = 0.33, p < 0.02). Similarly, SP-B was related to CC16 (r = 0.39, p < 0.004). Stepwise multiple linear regression analysis suggested that serum SP-A and SP-B are influenced by age (approximately 20 and approximately 25% of variance, respectively), whereas CC16 is determined by renal function and, to a lesser extent, by body weight (approximately 63% of variance in total). We conclude that CC16 is cleared from blood by the renal route, whereas SP-A and SP-B are not. Serum SP-A and SP-B are influenced by age, which we speculate reflects increased damage to the alveolocapillary barrier.