Lipid and apoprotein changes during atorvastatin up-titration in hemodialysis patients with hypercholesterolemia: a placebo-controlled study.

BACKGROUND: Patients with end-stage renal disease commonly present with an atherogenic lipid profile characterized by the accumulation of triglyceride-rich, apoprotein B-containing "remnant" lipoproteins, small dense low-density lipoprotein, and low levels of high-density lipoprotein. They are at increased cardiovascular risk and may benefit from drastic lipid-lowering treatment with atorvastatin, a potent, broadacting lipid regulator. This study aims to assess the effects of atorvastatin on the lipid profile in hemodialysis patients, to determine wether atorvastatin is also effective at lowering lipid levels in this particular high-risk subgroup. METHODS: In this randomized, placebo-controlled, double-blind study in hemodialysis patients with hypercholesterolemia (n = 42, mean total cholesterol 243 +/- 33 mg/dl (6.3 +/- 0.8 mmol/l)), the efficacy of 4-weekly increasing doses of atorvastatin (10 - 40 mg daily) was investigated. Lipids and apoproteins were measured in plasma and isolated lipoprotein fractions. RESULTS: Mean total cholesterol and low-density lipoprotein cholesterol progressively decreased with increasing doses of atorvastatin (total cholesterol -33%, low-density lipoprotein cholesterol -43% after 12 weeks), while high-density lipoprotein cholesterol remained unchanged. Plasma levels of apoprotein B and apoprotein E were also significantly reduced by atorvastatin 10 mg, while up-titration to 20 and 40 mg daily provided additional benefits by lowering triglycerides and apoprotein C-III. At week 12, the fraction of small dense low-density lipoprotein was significantly reduced from 23% - 18%, and apoprotein B-containing intermediate-density lipoproteins were no longer detectable. CONCLUSION: In conclusion, atorvastatin not only treated hypercholesterolemia but also favorably affected the uremic lipid profile in patients on hemodialysis. Atorvastatin 4-weekly dose escalation up to 40 mg daily was well-tolerated. Further prospective studies are needed to evaluate the impact of this improved lipid profile on morbidity and mortality.

Renal impairment in patients with inflammatory bowel disease: association with aminosalicylate therapy?

BACKGROUND: In recent years, several case reports have been published suggesting an association between the use of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) and the development of chronic tubulo-interstitial nephritis. Apart from lesions associated to 5-ASA treatment, however, it is clear that IBD itself may also induce renal impairment, albeit the frequency is unknown. METHODS: During 1 year, all IBD patients seen at the outpatient clinic of 27 European centres of gastro-enterology were registered and screened for renal impairment controlling for a possible association with 5-ASA therapy. Patients were questioned about their medical and drug history and their IBD disease activity. Renal screening (calculated creatinine clearance) was performed at baseline, after 6 and 12 months. RESULTS: Included patients (n = 1,529) had a mean age of 39 (range 14-98), 56% had Crohn's disease, 42% ulcerative colitis and 2% indeterminate colitis. Half of the patients used 5-ASA during the study period. Decreased creatinine clearance was observed in 34 patients, among them 13 with chronic renal impairment. Comparing patients with and without renal impairment, no difference could be observed in 5-ASA consumption. In contrast, patients with renal impairment were significantly older, had a lower body mass index and showed a higher frequency of male sex, bowel resection and stoma. CONCLUSION: Although the association between 5-ASA therapy and chronic tubulo-interstitial nephritis is clearly described in several case reports, this prospective study came to the reassuring conclusion that renal impairment in IBD patients is not frequently observed and is rarely associated with 5-ASA therapy.

The predictive value of cardiac troponin T measurements in subjects on regular haemodialysis.

BACKGROUND: Cardiac troponin T (cTnT) is a subunit of the cardiac actin-myosin complex, which leaks into the circulation when myocardial necrosis is present. Detection of cTnT is associated with a poor outcome in patients with unstable angina, and is a useful tool for risk stratification. The value of cTnT determination in patients with renal failure has been questioned, and the specificity of cTnT in this particular group has not been established. METHODS: In the present study, 94 patients at a single centre were followed prospectively after three determinations of cTNT, at 1-month intervals. The outcome after 12 months was chosen as the end-point. cTnT was measured using both a quantitative chemiluminiscence immunoassay and a qualitative rapid bedside immunoassay on a test strip. The maximum of three measurements was used and was correlated with different parameters and outcome. The following statistical tests were performed: Kaplan-Meier analysis, Cox's proportional regression analysis for measuring survival and logistic regression for analysing factors influencing cTnT. RESULTS: Forty seven of the 94 patients had a positive cTnT by test strip defined as >0.10 ng/ml. Twenty four patients died in the follow-up period (14 from cardiovascular causes). Twenty of the 24 non-survivors had an increased cTnT by test strip and 23 had increased cTnT by laboratory immunoassay. The outcome analysed by a Cox's proportional regression analysis showed that the factors which influenced survival significantly were cTnT, the presence of ischaemic heart disease, C-reactive protein (CRP) and prealbumin. A logistic multivariate analysis revealed that age and CRP significantly influenced cTnT. A good correlation was found between cTnT determined by test strip and in the laboratory. CONCLUSION: cTnT is elevated in a large number of patients on regular haemodialysis and is a significant independent predictor of outcome. Increased cTnT is significantly predicted by age and CRP.

Isotretinoin-induced vasculitis imitating polyarteritis nodosa, with perinuclear antineutrophil cytoplasmic antibody in titers correlated with clinical symptoms.

The adverse effects of retinoids on bones and joints are being increasingly documented. A case is reported in which isotretinoin was considered responsible for polyarteritis-like vasculitis. Perinuclear antineutrophil cytoplasmic antibodies were present in titers that correlated with clinical and laboratory test abnormalities.

Pharmacokinetics of linsidomine (SIN 1) after single and multiple intravenous short infusions in patients with renal insufficiency.

Pharmacokinetic measurements were performed in two groups of patients with coronary heart disease (CHD) after single and multiple dosing of 2 mg linsidomine (SIN 1). The drug was administered by intravenous short time infusion in 12 CHD-patients with renal insufficiency (RI group, Clcr: 11 +/- 6 ml/min) and in 12 CHD-patients with normal kidney function (control group, Clcr: 88 +/- 22 ml/min). The measurement of plasma concentration time courses of total SIN 1C (SIN 1 + SIN 1C) was found to be suitable for an estimation of the SIN 1C related half-life of the terminal phase (t50% = 1.5 +/- 0.5 h), as SIN 1 was eliminated from plasma rapidly (t50% = 12 to 20 min). Furthermore, the mean total SIN 1C plasma profiles were equal after single and multiple administration of the drug giving evidence that SIN 1C is not accumulating during repetitive dosing of SIN 1 in patients with renal disease. The mean maximum renal fraction of total SIN 1C excretion of RI-subjects (fe = 0.8 +/- 0.8% of dose) was significantly different from the corresponding mean value of the control group (fe(N) = 5.8 +/- 5.1% of dose). No differences were found for fe and fe(N) between day 1 and day 4. As SIN 1 is degraded in plasma very rapidly and as SIN 1C is cleared mainly extrarenally, any restrictions concerning repetitive SIN 1 dosage regimen should not be considered for CHD-patients with renal failure.

Pharmacokinetics of enoxacin and its oxometabolite following intravenous administration to patients with different degrees of renal impairment.

Enoxacin is a fluorinated quinolone with potential clinical use in the treatment of serious infections. Twenty-three patients (age, 19 to 87 years) with different degrees of renal function, including a group undergoing chronic hemodialysis, received enoxacin (400 mg) by intravenous infusion (1 h). Blood samples were collected before infusion; at the end of infusion; and at 5, 10, 20, 30, 45, 60, 90, and 120 min and 3, 4, 6, 12, 18, 24, 48, and 72 h after infusion. Enoxacin and oxoenoxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters (mean +/- standard deviation) were calculated by using a noncompartmental PK model according to creatinine clearances (in milliliters per minute). Total clearance of enoxacin decreased from 4.95 +/- 1.16 ml/min per kg in the group with normal creatinine clearance to 0.76 +/- 0.21 ml/min per kg in the patients with severe renal failure (creatinine clearance, less than 15 ml/min), whereas the elimination half-life increased from 4.5 +/- 1.0 to 20 +/- 5 h, respectively. The elimination of oxoenoxacin (the main metabolite of enoxacin) in urine was markedly decreased when creatinine clearance was less than 15 ml/min. Hemodialysis removed an insignificant amount of enoxacin and oxoenoxacin. These data indicate that as creatinine clearance falls below 30 ml/min, the daily enoxacin dose should be reduced by half. During prolonged administration of enoxacin to patients with creatinine clearances of less than 30 ml/min, the accumulation of oxoenoxacin might lead to unexpected side effects.

Effect of chronic oral testosterone undecanoate administration on the pituitary-testicular axes of hemodialyzed male patients.

Testosterone undecanoate (TU) or placebo was administered orally (for 12 weeks) in a double blind study, to 19 patients with chronic renal insufficiency on hemodialysis in a daily dose of 240 mg. Effect on plasma testosterone (T), dihydrotestosterone (DHT), androstenedione (A), 110H androstenedione (110A), FSH, LH and PRL concentration and the pituitary responsiveness to LH-RH/TRH stimulation was studied. These hormone levels were determined before the study and after 6 and 12 weeks of treatment. There was a rise in plasma androgen concentration in all treated patients. Mean plasma DHT, A and 110A increased at 12 weeks from 0.3, 0.85 and 1.13 ng/ml to 1.13 (p less than 0.05), 1.4 (p less than 0.05) and 1.44 (p less than 0.05) respectively. There was no change in plasma T or free testosterone. However, basal LH, FSH fell progressively from 5.51 and 5.51 ng/ml to 2.13 and 1.84 ng/ml (p less than 0.05). The level of significance of these changes was confirmed when the response to LH-RH was considered. Basal plasma PRL also decreased from 376 microU/nl to 306 (p less than 0.05), but PRL response to TRH remained unchanged. In contrast, none of these modifications were observed in placebo-treated patients. We conclude that oral TU restored to normal the pituitary-testicular axis. This form of treatment should be preferentially chosen instead of intramuscular injections in these frequently heparinized patients on hemodialysis.

Erythromycin prophylaxis for Legionnaire's disease in immunosuppressed patients in a contaminated hospital environment.

Between January 1 and June 30, 1983, immunosuppressive drugs were administered in 20 renal transplant recipients undergoing 23 rejection episodes and in 3 patients with renal failure secondary to systemic disease. Legionella pneumophila, serogroup 1, pneumonia was diagnosed on 12/26 (47%) occasions. In an attempt to decrease this high rate, a program of erythromycin prophylaxis was instituted for every new patient who received immunosuppressive chemotherapy until eradication of the organism from the water supply could be realized. From July 1, 1983 to April 30, 1984, erythromycin prophylaxis (1.5-3 g/day by mouth) was administered during 39 episodes of high-dose immunosuppression (20 kidney graft recipients and 4 patients with systemic diseases); no cases of Legionnaire's disease were recorded. During the same period, erythromycin prophylaxis was withheld from 9 other high-dose immunosuppression episodes (7 kidney graft recipients and one patient with sarcoidosis); 5 cases of Legionnaire's disease occurred (56%) in this group. We conclude that erythromycin effectively protects immunocompromised patients in an environment contaminated with L pneumophila.

Complications related to subclavian catheters for hemodialysis. Report and review.

Personal experience with subclavian vein cannulations for hemodialysis are given, and the pertinent literature on the subject is reviewed. Two hundred subclavian dialysis catheters were placed in 148 patients who kept them in place for a total of 2,798 days. Immediate complications were two pneumothoraxes and two hemothoraxes due to subclavian artery puncture. Seventeen cases of bacteremia were related to subclavian catheter infections. In 1 case, a complication of sepsis was a vertebral osteomyelitis. Clinical evidences of subclavian vein thrombosis occurred in 5 cases. Life-threatening complications were met in 2 cases: 1 with pericardial tamponade due to right atrium perforation and 1 with mediastinal hematoma and right hemothorax due to superior vena cava perforation. Review of the literature indicates that pneumothoraxes and/or hemothoraxes occurred in 1.7% of the catheter insertions and that sepsis related to subclavian dialysis catheters occurred in 8.9% of the patients. As systematically investigated subclavian vein thrombosis involved at least 50% of the patients. Our 2 personal cases of life-threatening complications and 14 similar cases of the literature were analyzed: left subclavian catheters were associated with superior vena cava perforation with right hemothorax or mediastinal hematoma, while right subclavian catheters gave atrial perforation with pericardial tamponade. Death occurred in 3 of 16 cases, and emergency surgery was required in 5 of 16 cases. Taking into account all these complications, recommendations are made for the use of subclavian dialysis catheters.

Infections associated with subclavian dialysis catheters: the key role of nurse training.

Two hundred subclavian dialysis catheters were placed in 148 patients who kept them in place for a total of 2,798 days. Catheterization time ranged from 1 to 79 days with an average of 14.0 +/- 1.0 days per catheter and 18.9 +/- 1.0 days per patient. Twenty nine catheters were infected, 17 of which were the source of bacteremias due to Staphylococcus epidermidis in 13 cases and to Staphylococcus aureus in 4 cases. The incidence of sepsis was not significantly greater in diabetic patients, in patients with corticotherapy or in patients presenting an underlying systemic disease. On the contrary, the incidence was greater in hospitalized patients (15 bacteremias during 1,948 catheter days) than in ambulatory patients (2 bacteremias during 850 catheters-days) as well as during a period corresponding to a greater number of untrained nurses enrolled in the dialysis team. During this period, 6 sepsies occurred in 19 catheters (other periods: 7 sepsies/116 catheters, p less than 0.01). 6 of 28 nurses had less than 3 months of professional experience (other periods: 1 of 25, p less than 0.01). These data underline the key role of nurse training in the prevention of catheter-related infections.

[Comparative effects of oral water load of different mineral compositions on the excretion of ions and oxalic acid]. / Effets comparés sur l'excrétion des ions et de l'acide oxalique de charges orales en eaux de compositions minérales différentes.

The effects on urinary excretion of a 1500 ml daily load of three drinking waters with different ionic contents were studied in six normal subjects. Diuresis was similarly increased by the three waters of an amount equal to the load. Urine output of urea, creatinin, uric acid, phosphate, potassium, magnesium was not significantly modified by the three waters as compared to a control period. Natriuresis was significantly increased following the intake of the water which contained sodium as well as calciuria with the water containing calcium. Urine output of oxalate was increased by the three waters in correlation with the free water content of the load. This effect is probably due to a reduction in passive tubular reabsorption of oxalate since a similar effect was observed with an equivalent water load given by intravenous route. Nevertheless, due to the dilution of urine, the index of urine saturation for calcium oxalate was diminished by the three waters.