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 simvastatin treatment on the dyslipoproteinemia in CAPD patients.

HMG-CoA reductase inhibitors have been proven effective in decreasing the plasma cholesterol levels in patients affected with various forms of hypercholesterolemia, familial dysbetalipoproteinemia, familial combined hyperlipidemia and in nephrotic and diabetic dyslipidemia. The purpose of this study was to monitor and evaluate the efficiency and safety of the therapy with simvastatin, an HMG-CoA reductase inhibitor, in a group of patients treated by continuous ambulatory peritoneal dialysis (CAPD) with severe hypercholesterolemia. Monitoring of the changes occurring in the various lipids and apolipoproteins in these patients included the measurements of the plasma lipids and apolipoproteins A-I, A-II, B, C-II, A-IV and Lp(a). Lipoproteins were separated by gel filtration, on a Superose 6HR column, before and after 24 weeks of treatment. The patterns were compared to those observed in a group of primary hyperlipidemic patients treated with Lovastatin, a compound of the same class. The drug was well tolerated by the CAPD patients and no adverse reaction was observed. In addition to the decrease of the total and LDL cholesterol, similar to that reported in other groups of patients, we further observed a decrease of the apo E concentration in both the CAPD and the hyperlipidemic patients. This decrease was especially pronounced in the HDLE fraction and could involve an upregulation of the apo B-E and/or apo E receptor. These results should provide information about the mechanism of action of this drug in patients with end-stage renal disease.

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.

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.

Decrease in renal function due to sulphinpyrazone treatment early after myocardial infarction.

Twenty-nine patients with recent myocardial infarction were randomly allocated to a placebo group (n = 14) and to a group (n = 15) who received sulphinpyrazone, 4 x 200 mg daily for 7 days. Renal function significantly and transiently deteriorated in the sulphinpyrazone group compared to the placebo group. In the sulphinpyrazone group the 24 hour-urinary prostaglandin E2 and kallikrein excretion were suppressed. These data suggest that the decrease in renal function caused by sulphinpyrazone early after myocardial infarction could be mediated by an inhibition of renal prostaglandin and/or kallikrein-kinin synthesis.

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.

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.

Prostaglandin-kallikrein-renin system during acute sulphinpyrazone administration in healthy volunteers.

Sulphinpyrazone administered acutely to 8 healthy male volunteers decreased the urinary (U) excretion of prostaglandin (PG)E2 (p less than 0.01)( but not of PGF2 alpha. Also, the ratio U-PGE2/U-PGF2 alpha and the urinary excretion of kallikrein declined (p less than 0.001 and p less than 0.05 respectively). Sulphinpyrazone therapy caused a significant inhibition of PRA (p less than 0.05). Renal function, as assessed by serum creatinine and creatinine clearance, remained constant in these normal men, possibly related to the fact that both the vasodilatory PG-kallikrein-kinin system and the vasoconstrictive renin-angiotensin system were inhibited by sulphinpyrazone. However, it is conceivable that in clinical situations where vasoconstrictive stimuli are enhanced, sulphinpyrazone can disturb the balance between those systems and can lead to an impaired renal function.

Takayasu's arteritis in a young Caucasian female: case report and review.

We report a case of a 24-year-old Caucasian woman presenting with fatigue, weight loss, a cardiac murmur, anaemia and biochemical markers of inflammation due to Takayasu's arteritis (TA), a vasculitis of the aorta and large vessels that typically affects young women. The rarity of the disease, the great variability in presentation together with the absence of specific symptoms as well as the absence of specific biochemical markers, makes early diagnosis difficult. Besides (magnetic resonance) arteriography, new promising diagnostic tools are discussed, including transoesophageat echocardiography (TEE) and Positron Emission Tomography (PET). Nevertheless, a high index of suspicion remains the key to an early diagnosis, and hence a better prognosis, of TA.

Management of therapy-resistant systemic lupus erythematosus with rituximab: report of a case and review of the literature.

Therapy of systemic lupus erythematosus (SLE) with major organ involvement consists of aggressive immunosuppression with glucocorticoids and cytotoxic agents. When remission is achieved, maintenance therapy is begun to reduce the risk of relapse while minimizing toxicity. Remission with standard therapy is, however, not always achieved. We discribe a women with SLE and microangiopathic haemolytic anaemia and thrombocytopenia, pneumonitis and nephritis refractory to high-dose steroids, pulse cyclophosphamide, plasmapheresis and intravenous immunoglobulins. The anti-CD20 monoclonal antibody rituximab was administered, resulting in major clinical and biochemical improvement. Therapy-resistant SLE generally has an ominous prognosis. A few anecdotal reports and small open studies describe beneficial effects of rituximab in these cases. Rituximab may be a promising new approach to improve the dismal outcome of therapy-resistant SLE.

Pseudoxanthoma elasticum.

An 64-year-old woman had pseudoxanthoma elasticum (PXE) with the characteristic skin and oculair findings. She had no associated systemic systems and no family history of PXE. The case-report is reviewed with regard to etiology, clinical features, diagnosis, inheritance and, particularly, management.

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.

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.

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.