Increased silicon levels in dialysis patients due to high silicon content in the drinking water, inadequate water treatment procedures, and concentrate contamination: a multicentre study.

BACKGROUND: Although silicon is considered as an essential element, little is known about the basic effects and clinical significance of increased concentrations of the element in dialysis patients. METHODS AND RESULTS: In a multicentre study we found silicon levels in haemodialysis (HD) patients to be markedly increased. In these patients silicon concentrations were significantly higher than those noted in subjects with normal renal function as well as in patients with chronic renal failure not yet in dialysis and patients treated by continuous ambulatory peritoneal dialysis (CAPD). Moreover we noted that in both HD and CAPD patients mean silicon levels differed from one centre to another. Also, was there in the HD population a significant difference in serum silicon levels among patients from different countries. In HD patients differences in serum silicon levels were either due to the use of silicon contaminated dialysis fluids or an increased oral intake of the element mainly originating from the high silicon content of the drinking water. Silicon contamination of the dialysis fluid was found to be due to either the use of reverse osmosis membranes that insufficiently retain the element during water treatment or by the addition of concentrates containing high amounts of silicon. Using a recently developed high-performance liquid chromatographic/atomic absorption spectrophotometric (HPLC/ETAAS) hybrid technique, we found silicon in serum to be present as a low-molecular-weight non-protein-bound component, which in the presence of a low silicon dialysate is adequately removed during treatment. CONCLUSIONS: The clinical relevance of increased serum silicon levels is not yet known and as such deserves further investigation. In view of the controversy that exists on the element's assumed protective as well as toxic role in the development of some (aluminium-related) neurodegenerative diseases and its vital role in bone formation, monitoring of the silicon levels in serum, tap water, and dialysis fluids might become important.

Staphylococcus aureus infections in haemodialysis patients: pathophysiology and use of nasal mupirocin for prevention.

Staphylococcus aureus is the most frequently (42%) isolated micro-organism during bacteraemic episodes in haemodialysis patients. Nasal carriage of S. aureus is of major importance in determining the risk of subsequent infections. Indeed, nasal carriage of S. aureus is highly prevalent in uraemic patients from the onset of maintenance dialysis therapy. The strains isolated simultaneously from the nares and the hands are usually the same. Likewise, infecting S. aureus strains and those isolated from nasal surveillance cultures obtained in the same patient are usually similar. S. aureus infections in haemodialysis patients are thus mostly to be considered as auto-infections. The nares are therefore an elective site for the prevention of S. aureus infections in haemodialysis patients. This has been demonstrated with oral rifampin, and more recently with nasal mupirocin, which is highly effective. Long-term application of nasal mupirocin (e.g. once per week) is cost-effective and is only rarely associated with the emergence of mupirocin-resistance in S. aureus.

[Epidemiology and prevention of Staphylococcus aureus infections during hemodialysis]. / Epidémiologie et prévention des infections à Staphylococcus aureus en hémodialyse.

Staphylococcus aureus is the pathogen most often isolated from blood during bacteraemic episodes in haemodialysis patients (42%). The pathophysiology of these infections is discussed and a prophylactic strategy is proposed. Nasal carriage of S. aureus, found in 42% of haemodialysis patients, plays a major role in its cutaneous dissemination and hence in the risk of infection by this microorganism. Long-term use of nasal mupirocin in haemodialysis patients with nasal carriage of S. aureus (t.i.d. for 3 to 5 days, followed by once a week) led to a decrease in the yearly incidence of S. aureus bacteraemia from 0.097 to 0.024 (p < 0.01). Tolerance was excellent. This chemoprophylaxis results in substantial savings. When applied as proposed (only nasal application), the long-term use of mupirocin only very rarely leads to the emergence of mupirocin-resistance in S. aureus (1 case in 165 patient-years).

Nasal mupirocin ointment decreases the incidence of Staphylococcus aureus bacteraemias in haemodialysis patients.

The incidence of S. aureus bacteraemia in a haemodialysis unit was studied over 2 years (167.75 patient-years of follow-up) during which nasal calcium mupirocin was used to eradicate nasal S. aureus carriage; this incidence was compared to that previously observed in the same unit before the use of nasal mupirocin (185.8 patient-years). Nasal mupirocin led to eradication of nasal S. aureus carriage in 96.3% of surveillance cultures and to a fourfold reduction in the incidence of S. aureus bacteraemia per patient-year, from 0.097 before mupirocin to 0.024 with mupirocin use (P = 0.008). Once or thrice weekly maintenance regimens of mupirocin were equally efficacious. The incidence of bacteraemia caused by other micro-organisms was not significantly affected. One single mupirocin-resistant isolate was identified in a nasal surveillance culture. Eradication of S. aureus from the nares did not lead to overgrowth by other micro-organisms. Chemoprophylaxis with nasal mupirocin in haemodialysis patients is cost-effective.

Iron overload in haemodialysis patients increases the risk of bacteraemia: a prospective study.

The incidence of bacteraemia in relation to the degree of transfusional iron overload was studied prospectively in patients from one haemodialysis unit over a 2-year period, with a total follow-up of 181.3 patient-years in 158 patients. Every 3 months, the patients were classified according to the serum ferritin in one of three groups: less than 500, 500-1000 or greater than 1000 micrograms/l. Twenty-nine episodes of bacteraemia were recorded over 181.3 patient-years (yearly incidence of 0.160). The yearly incidence of bacteraemia was 0.1173 and 0.1101 for ferritin less than 500 and 500-1000 micrograms/l (no significant difference), with a cumulative incidence for both groups of 0.1164. In the ferritin greater than 1000 micrograms/l group, the incidence was 0.3404 (P less than or equal to 0.005 versus the ferritin less than or equal to 1000 micrograms/l group). After stratification for patient's age (at inclusion in the study) and duration of haemodialysis therapy, the higher incidence of bacteraemia in the ferritin greater than 1000 versus less than or equal to 1000 micrograms/l groups persisted (P less than or equal to 0.005). This prospective study confirms previous retrospective studies in showing that acquired transfusional iron overload in haemodialysis is associated with a greater risk of bacteraemia.

The influence of calcium mupirocin nasal ointment on the incidence of Staphylococcus aureus infections in haemodialysis patients.

Mupirocin was used in haemodialysis patients in an attempt to eradicate nasal carriage of Staphylococcus aureus and to prevent infection caused by this microorganism. The effectiveness of calcium mupirocin as a 2% nasal ointment OB2 (16 patients for 104 patient-months) was compared to that of placebo (18 patients for 147 patient-months) in a double-blind study. Mupirocin or placebo were applied in both anterior nares thrice daily for 2 weeks and subsequently three times weekly for a total of 9 months. During therapy, S. aureus was recovered from only 6% of the nasal cultures in the mupirocin group compared to 58% in the placebo group (P less than or equal to 0.01). Only one S. aureus infection was documented in the mupirocin group compared to six in the placebo group (P less than or equal to 0.05). The S. aureus strain causing the single infection in the mupirocin group was of a different phage type to that of the original nasal strain. In contrast, at least four of the six strains causing infection in the placebo group were of similar phage type to the original nasal strain. All S. aureus isolates remained mupirocin sensitive (MIC less than or equal to 1 mg/l). In conclusion, mupirocin nasal ointment was effective in eradicating nasal carriage of S. aureus and in preventing S. aureus infections in patients on haemodialysis.

Comparative pharmacokinetics of recombinant erythropoietin administered by the intravenous, subcutaneous, and intraperitoneal routes in continuous ambulatory peritoneal dialysis (CAPD) patients.

The single dose pharmacokinetics of recombinant human erythropoietin (r-HuEPO) were compared in six continuous ambulatory peritoneal dialysis (CAPD) patients after intravenous (i.v.), subcutaneous (s.c.), and intraperitoneal (i.p.) administration of 300 U/kg. Intravenous administration gave results close to those obtained in hemodialysis patients, with a half-life of 11.2 h and a volume of distribution of 5.0% of body weight. After subcutaneous administration, the serum concentration rose slowly to plateau between 24 and 36 h, the area under the serum concentration vs. time curve from 6 to 72 h being 18.2% of that after intravenous administration. After intraperitoneal administration, the serum concentration was even lower, the area under the curve from 0 to 24 h was between 2.5 and 3.6% of that after intravenous administration, and 80% of the administered dose was recovered in the first peritoneal effluent after a 4-h dwell time.

Itraconazole pharmacokinetics in patients with renal dysfunction.

The single-dose pharmacokinetics of 200 mg of oral itraconazole were studied in seven uremic patients, seven patients treated by hemodialysis, and five patients treated by continuous ambulatory peritoneal dialysis. Plasma concentration-versus-time profiles showed wide intersubject variation. This study could not demonstrate any significant effect of renal dysfunction and hemodialysis or continuous ambulatory peritoneal dialysis treatment upon the pharmacokinetics of itraconazole, and firm conclusions concerning dosing in such patients should await confirmation of our data in a larger patient population.

Pharmacokinetics of nisoldipine in renal dysfunction.

The pharmacokinetics of nisoldipine have been studied after oral administration of one 10 mg tablet to 3 groups of patients: Group A (n = 8) with a mean creatinine of 90 ml/min, Group B (n = 8) with a mean creatinine clearance of 12 ml/min and Group C of 12 patients on maintenance haemodialysis. All of them were studied off-dialysis and 7 were also studied on a dialysis day. No significant differences were observed between Groups A, B and C (on an interdialysis day) in AUC (0-7h), tmax, Cmax and plasma protein binding. Unchanged nisoldipine could not be recovered from the urine in any patient. Haemodialysis did not significantly affect AUC, tmax and Cmax, and nisoldipine could not be detected in the dialysate. The results indicate that the dose of nisoldipine need not be changed in patients with renal dysfunction, and that a supplementary dose is not required after haemodialysis. Blood pressure in the uraemics fell more than in the patients with good renal function.

Nabumetone pharmacokinetics in patients with varying degrees of renal impairment.

The pharmacokinetics of 1 g of oral nabumetone were studied in 20 patients divided into three groups according to the creatinine clearance rate of each. Pharmacokinetic assessment was made on the presence of the major and active metabolite found in the plasma, 6-methoxy-2-naphthylacetic acid, BRL 10720. Although the differences in the kinetic parameters measured in the three groups of patients were not statistically significant, that the drug should be used with care in patients with impaired renal function until additional data are available.

Multiple dose pharmacokinetics of intravenous acyclovir in patients on continuous ambulatory peritoneal dialysis.

Once daily 60 min iv infusions of acyclovir at 2.5 mg/kg were administered to six uraemic patients (three male, three female of mean age 52 years and body weight 60 kg) treated by continuous ambulatory peritoneal dialysis (CAPD). Blood and dialysate samples were taken for analysis of acyclovir by radio-immunoassay. A three-compartment pharmacokinetic model was found necessary to explain the profiles obtained. Steady-state was reached by the third day, with little change in mean peak or trough plasma levels between day one (25 and 3 microM) and day five (29 and 4 microM). Mean total plasma clearance was 46 ml/h/kg, of which 12% was due to peritoneal dialysis. The model parameters predicted efficient transfer of acyclovir from the peritoneum to plasma, such that hypothetical peritoneal dosing might give 91% bioavailability. In patients treated by CAPD, iv acyclovir should be administered at 2.5 mg/kg/day.

Impairment of renal function due to sulphinpyrazone after coronary artery bypass surgery: a prospective double-blind study.

In this randomized, double-blind, placebo-controlled trial the renal function was studied in 60 patients recovering from coronary artery bypass surgery treated with a daily dose of 800 mg sulphinpyrazone (SP) or 880 mg acetylsalicylic acid (ASA) or placebo. Serum creatinine level increased (p less than 0.05) during the first 2 days of SP treatment, but returned to its baseline level within 4 days under maintained therapy; during ASA and placebo therapy no significant changes occurred. Serum urea levels decreased (p less than 0.01) during ASA and placebo treatments as time from surgery subsided; the decrease of serum urea level was delayed in the SP group compared with the ASA and placebo groups. Urinary excretion of prostaglandin E2 (PGE2) was significantly decreased (p less than 0.01) during ASA treatment; in the SP group, urinary PGE2 excretion tended also to decrease during the first days of treatment, the decrease being significant only on the 4th day (p less than 0.01). The urinary excretion of kallikrein decreased significantly only in the SP group (p less than 0.01), while the changes in the ASA and placebo group were not significant. We suggest that the rapidly reversible acute renal impairment during SP therapy was probably due to a transient renal ischemia caused by a drug-related decrease in urinary kallikrein excretion rather than by renal prostaglandin inhibition.

The pharmacokinetics of ciprofloxacin in patients with impaired renal function.

Pharmacokinetics of ciprofloxacin after single oral administration of 250 mg were studied in patients with and without renal failure. Ciprofloxacin concentrations were measured by HPLC. The elimination half-life was 8.7 +/- 0.9 h (mean +/- S.E.M.) in six renal failure patients not on haemodialysis, as compared to 4.4 +/- 0.2 h in six patients with normal renal function. The urinary recovery of unchanged ciprofloxacin was 5.3 +/- 1.7% of dose over 24 h in the renal failure patients, as compared to 37.0 +/- 3.7% in the patients with normal renal function. In haemodialysis patients, the half-life was 5.8 +/- 0.9 h on an interdialysis day, and 3.2 +/- 0.4 h during haemodialysis.

Lipoprotein distribution and composition in the human nephrotic syndrome.

Plasma lipoprotein profiles were quantitated in 9 patients with the nephrotic syndrome. Six subjects were studied both during an active proteinuric phase and during a remission phase without proteinuria. During the proteinuric phase, the plasma triglyceride, cholesterol and apo B levels were markedly increased, whereas the HDL cholesterol, apo A-I, and apo A-II concentrations were normal. Analysis of the distribution and composition of the lipoprotein subclasses, separated by isopycnic ultracentrifugation, showed typical patterns characterized by: (1) elevated apo B-rich VLDL and LDL fractions, (2) the presence of a denser LDL subfraction, floating at d 1.053 g/ml, which contained about 35% of LDL cholesterol and apo B and (3) a redistribution among HDL subclasses. The HDL2b (d 1.063-1.100 g/ml) fraction was markedly decreased, while the HDL2a + 3a (d 1.100-1.150 g/ml) and HDL3b + 3c (d 1.150-1.210 g/ml) subclasses were moderately elevated. The decreased cholesterol and apo A-I contents of HDL2b therefore counterbalanced their increase in HDL2a + 3a and HDL3b + 3c, resulting in normal plasma HDL cholesterol and apo A-I concentrations. When reinvestigated during a remission phase without proteinuria, the nephrotic patient's overall lipoprotein distribution and composition were similar to those in healthy controls. The combination of several factors such as the presence of elevated apo B-rich VLDL, IDL and LDL, together with decreased HDL2 cholesterol and HDL2 apo A-I suggests that nephrotic patients are at increased risk for atherosclerosis.

Effect of renal function and dialysis on temocillin pharmacokinetics.

Temocillin pharmacokinetics in renal impairment were investigated following an intravenous bolus injection of 15 mg/kg. The 28 patients were divided into 5 groups of varying renal function, from normal to uraemic [including a group being treated with haemodialysis and a group on continuous ambulatory peritoneal dialysis (CAPD)]. The distribution of temocillin into the tissues was not affected by renal dysfunction. Uraemia as compared to normal renal function resulted in a 4.3-fold decrease in temocillin clearance and a 3.1-fold decrease in urinary recovery over 24 hours, as well as a 5- and 3.7-fold increase in the beta half-life and the area under the curve (AUC), respectively. Haemodialysis doubled the serum clearance and halved the beta half-life of temocillin in the uraemic subject, but CAPD over 24 hours eliminated only 8% of the temocillin dose, resulting in a minimal change in pharmacokinetics. Temocillin dosage adjustments in renal failure are proposed.