1 Eight patients with end‐stage renal insufficiency on maintenance haemodialysis, and seven patients with newly diagnosed hyperthyroidism, received a single intravenous dose of diazepam, followed by blood sampling over the next 7 days. Fifteen healthy volunteer controls, matched with patients for age and sex, were similarly studied. 2 Diazepam half‐life in renal failure patients (mean 37 h) was greatly reduced compared to controls (mean 92 h, P less than 0.05) and clearance of total (free plus bound) diazepam correspondingly increased (0.94 v 0.34 ml min‐1 kg‐1, P less than 0.01). 3 However, differences were largely related to disease‐related changes in drug binding and distribution. Mean unbound fraction of diazepam in plasma of renal patients (7.0%) was greatly increased over controls (1.4%, P less than 0.01) and Vd of unbound diazepam greatly reduced (57 v 157 l/kg, P less than 0.01). 4 Clearance of pharmacologically active unbound diazepam (intrinsic clearance) was not significantly different between renal patients and controls (23 vs 30 ml min‐1 kg‐1). 5 None of the kinetic variables for total or unbound diazepam in thyrotoxic patients differed significantly from those in controls matched for age and sex. 6 End‐ stage renal failure (or its associated drug therapy) alters diazepam protein binding and distribution, but does not significantly change clearance of unbound drug. Thyrotoxicosis does not influence diazepam kinetics.

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The pharmacokinetics of a single 30-mg oral dose of oxazepam was evaluated in seven patients with chronic renal failure on maintenance hemodialysis and in seven healthy controls matched for age and sex. Based on total (free plus bound) serum oxazepam concentrations, elimination half-life was prolonged in renal patients compared to controls (22 vs 8 h, p less than 0.001) and volume of distribution increased (3.0 vs 1.4 1/kg, p less than 0.02). However, total clearance was similar between groups (1.8 vs 1.9 ml/min per kilogram). These findings were confounded by the increased oxazepam free fraction in serum of renal failure patients (10.3%) as compared to healthy controls (4.3%). Correction for differences in binding indicates similar distribution of unbound oxazepam between groups, but reduced clearance of pharmacologically active unbound oxazepam in renal patients (18 vs 45 ml/min per kilogram). Oxazepam dosage, therefore, may require downward adjustment for renal failure patients on hemodialysis.

Using the Seldinger technique, a total of 5306 percutaneous femoral vein catheterisations were performed in the course of ten years. Two-catheter venovenous dialysis was performed 2357 times and single-needle technique 592 times. There were five important complications: severe retroperitoneal bleeding after perforation of the external iliac vein three times, fatal bleeding from the femoral artery once, and reversible damage to the femoral nerve once. The results indicate that for every 1000 percutaneous femoral-vein catheterisations one must expect one severe complication. However, by using the correct catheter technique, especially careful manipulation of the wire, complications can be largely avoided.

It is uncertain whether nonnocalcemic, nonnocalciuric patients with calcium nephrolithiasis have a disorder of calcium metabolism. We studied the effect of a parathyroid extract (PTE) infusion (1.4 U/kg body weight) on the urinary cyc1ic AMP excretion in 16 such patients. For comparison, we investigated groups of nonnal individuals and patients with primary hyperparatyhroidism, renal insufficiency and different gastrointestinal diseases. The increase of cyclic AMP above basal excretion in patients with nephrolithiasis was only 1.2 ± 0.3 J.Lmol/h (mean ± SEM), versus 2.5 ± 0.5 J.lmol/h in normal subjects (p < 0.05) although the basal excretion was similar. Patients with renal insufficiency had low basal excretion of cyclic AMP and little stimulation of excretion by PTH (in'crease, 0.3 ± 0.06 J.lmol). Patients with primary hyperparathyroidism had high baseline cyclic AMP excretion but subnonnal stimulation by PTE (increase, 0.46 ± 0.13); in contrast, patients with different gastrointestinal disease had high baseline excretion and supranormal stimulation of cyclic AMP excretion (increase, 5.2 ± 0.6). We speculate that an impaired response to PTH might be involved in the slightly increased urinary calcium excretion in ]lonnoca1cemic stone fonners suggested by others.