Prediction of creatinine clearance from serum creatinine concentration based on lean body mass.

An equation for predicting endogenous creatinine clearance (CrCl) in adults and children (with both stable and unstable renal function) from serum creatinine concentration is presented. The predictions are compared with four other available estimating methods, bases on values in 110 subjects with renal impairment of widely differing degrees. In patients with stable and with unstable renal function the corelaion between measured and predicted CrCl was better with the new equation. In patients with rapid changing renal function the new equation resulted in accurate predictions CrCl within a few hours after the change, as opposed to several with the other methods. The elimination rate constant of the aminoglycoside antibiotic amikacin correlated more precisely with CrCl values estimated from the new equation that with those measured doing 24 hr or with the other prediction methods.

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.

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.

[Quantitative determination of the main metabolites of acetylsalicylic acid/2nd communication: the concentrations of salicylic acid and its metabolites in patients with renal insufficiency (author's transl)]. / Quantitative Bestimmung der Hauptmetaboliten der Acetylsalizylsäure 2. Mitteilung: Die Konzentrationen an Salizylsäure und ihren Metaboliten bei niereinsuffizienten Patienten

Quantitative Determination of the Main Metabolites of Acetylsalicylic Acid / 2nd Communication: The concentrations of salicylic acid and its metabolies in patients with renal insufficiency 9 patients suffering from renal insufficiencies of varing degrees and treated regularly by hemodialysis were given 1.5 g Colfarit (microcapsulated acetyl salicylic acid) as a single dose. The concentrations of salicylic acid (SA), salicyluric acid (SU), further salicylic acid conjugates (SAC) and salicyluric acid conjugates (SUC) were determined in the blood plasma. Likewise urea and creatinine were determined. SA concentration decreased continually and, at the end of the trial (72 h after application), had vanished almost completely from the plasma of most patients. SU increased at first and decreased afterwards. With the exception of the dailysis time SAC and SUC increased during the trial. After 3 days the SUC level was more than 50% of total salicylate (SSS) in most patients. SSS (the sum of SA + SU + SAC + SUC) did not change very much before dialysis, but showed a rather high decrease during the first hours of dialysis. tafter dialysis the SSS levels rose again, apparently as a consequence of a redistribution and of the synthesis of conjugates with decreased tissue affinity. It could be shown that SSS in the blood plasma does not parallel SSS in the whole body. The interindividual variation of SA metabolism as well as the variation of the biological blank values was rather high. The results are discussed with regard to salicylate pharmacokinetics in renal insufficiency and to normal salicylate metabolism.

Pharmacokinetics of amikacin in patients with renal insufficiency: relation of half-life and creatinine clearance.

The half-life of amikacin after a single intramuscular injection was determined in patients with severe renal failure who received 3.75 mg of drug/kg and in patients with various degrees of renal function who received 7.5 mg of drug/kg. The relation of the half-life of amikacin to levels of serum creatinine is practically identical to that of kanamycin. However, although concentrations of serum creatinine remained practically unchanged, rates of creatinine clearance may by considerably decreased in older subjects. This decrease may result in overestimation of the rate of glomerular filtration and subsequent overdosage. Therefore, the half-life of amikacin should be derived from values of rates of creatinine clearance or be predicted with use of a nomogram. The calculated half-life values may be used for development of appropriate dosage schedules for patients with various degrees of renal function. Such schedules would ensure therapeutic levels of drug and avoid potentially toxic accumulation of antibiotic.