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The biocompatibility of a 1.1% amino acid-containing peritoneal dialysis fluid (AA-PDF) was compared to that of a 2.27% glucose-based peritoneal dialysis fluid (G-PDF). Peritoneal macrophages (PMO), isolated from the peritoneal dialysis (PD) effluents of 10 chronic ambulatory PD patients, were tested for their phagocytosis capacity and peak chemiluminescence response. A subset of PMO was cultured for 24 h with and without lipopolysaccharide (LPS) to study the release of interleukin-1 beta (IL-1 beta) and 8 (IL-8). As control, the interleukin release by blood monocytes of healthy donors was tested. The opsonic activity of the PD effluent was tested as well. Compared to PMO isolated from G-PDF, PMO from AA-PDF showed a significantly better phagocytosis capacity. There was no difference in the peak chemiluminescence response between PMO from AA-PDF and G-PDF. The release of IL-1 beta by unstimulated PMO isolated from the two fluids did not differ. Compared to control monocytes, however, PMO from both fluids showed a considerable spontaneous release of IL-1 beta. When stimulated with LPS, IL-1 beta production by PMO from G-PDF exceeded that of PMO from AA-PDF (p < 0.002). The release of IL-8 by PMO from G-PDF was significantly higher in comparison with PMO from AA-PDF, both spontaneously and after stimulation with LPS (p < 0.02). The opsonic activity of undiluted and to 75% diluted effluents was significantly higher for G-PDF than for AA-PDF (p < 0.01). Thus, compared to the regularly used G-PDF, the phagocytosis capacity as measure for PMO function seems to be better preserved after in vivo exposure to AA-PDF. In addition, the higher release of IL-1 beta and IL-8 by PMO isolated from G-PDF suggests a stronger intra-abdominal activation of PMO, with G-PDF acting as a chemical inflammatory agent. Whether the lower opsonic activity of the AA-PDF is more important for biocompatibility than the other parameters is not clear. Therefore, it is concluded that, although macrophage function is better preserved, it is not proven that the 1.1% AA-PDF studied has an improved biocompatibility compared to 2.27% G-PDF.

The effect of two different dialysate solutions with a calcium concentration of 1.25 and 1.75 mmol/l was evaluated in 14 patients, using a cross-over design. Patients were treated with each solution during a period of 6 months. Treatment with calcium supplements, vitamin D and aluminium hydroxide was adapted weekly, according to the results of blood chemistry. PTH, SAP, and ionized calcium were determined monthly, bone density with DXA and QCT before and after 6 months of treatment. During treatment with both 1.25 and 1.75 calcium dialysate (cad), the control of serum calcium and phosphate was similar. PTH did not change during either treatment. SAP decreased during treatment with 1.75, but remained stable with 1.25 mmol/l cad. Bone density evaluated with DXA remained unchanged during both treatments. QCT measured bone density increased from 101.29 +/- 13.50 to 106.79 +/- 13.14 mg/ml in the 1.75 cad group, while it did not vary in the 1.25 cad group, (107.75 +/- 13.48 versus 108.97 +/- 13.40 mg/ml). It is concluded that lowering the calcium content of the dialysate does not negatively influence the control of serum calcium and phosphate, nor does it aggravate hyperparathyroidism when vitamin D is administered simultaneously. Under the present conditions, osteopenia and possibly bone mineralization improve only in the group dialysed with 1.75 Ca.

Two similar cases of rapidly progressive fibrosing interstitial nephritis in young women who followed the same slimming regimen prompted us to conduct an epidemiological survey of the nephrology centres of Brussels and to further investigate the exact nature of this slimming treatment. Seven other women under the age of 50 in terminal or preterminal renal failure were admitted for dialysis in 1991 and 1992. They had all followed a slimming regimen in the same medical clinic. Renal biopsy samples in eight of the nine cases showed extensive interstitial fibrosis without glomerular lesions. Two of the patients were seen for the first time in terminal renal failure and were started immediately on dialysis. For the seven other women, the nephropathy was characterised by a rapid deterioration in renal function, with initial serum creatinine doubling within about 3 months. The clinic had specialised in slimming treatments for the previous 15 years without any problems. In May, 1990, therapy was changed, with the introduction of two Chinese herbs (Stephania tetrandra and Magnolia officinalis). In June, 1992, three of twenty-five randomly selected women who had followed the same regimen during at least 3 months from 1990 had impaired renal function. Chemical analysis of some brands of these Chinese herbs did not show nephrotoxic contaminants of fungal or plant origin (ochratoxin or aristolochic acid) or adulteration by diuretics or antiinflammatory drugs. However, the medicinal preparation of the capsules taken by patients had different alkaloid profiles from those expected in Chinese plants. The striking relation between a specific type of fibrosing interstitial nephritis in young women and a slimming treatment involving Chinese herbs adds support to the arguments against uncontrolled therapy with herbal preparations.

We present a patient acutely ill from severe tuberculous meningo-encephalitis, in whom acute hepatic and renal failure, due to intercurrent septic shock, precluded the administration of full systemic dosage of antituberculous drugs. Daily direct intraventricular administration of 5 mg rifampicin, via a subcutaneous Ommaya reservoir connected to a catheter placed in the right lateral cerebral ventricle, resulted in rapid improvement without neurological sequelae. Intraventricular rifampicin administration for 50 consecutive days was well-tolerated without local or systemic side-effects. In well-selected patients with severe tuberculous meningo-encephalitis, intraventricular rifampicin may safely and highly effectively be added to systemic antituberculous therapy.

A 66-year old tailor was admitted because of venous insufficiency of the left lower leg. During the hospital course, recurrent severe gastrointestinal blood loss developed. A classical approach was extended by enteroscopy and radionuclide scanning, followed by exploratory laparatomy with removal of two intra-abdominal sewing needles and a jejunal leiomyoma. After surgery, bleeding did not recur. This case illustrates the difficult diagnostic work-up of obscure gastrointestinal bleeding. It also shows that intra-abdominal sewing needles may migrate in the intestinal tract and remain silent during many years, eventually causing gastrointestinal bleeding.

Nephron loss leads to increased production of reactive oxygen intermediates. We measured the effect of carvedilol, a beta-blocking drug with radical scavenging properties, on renal function, glomerulosclerosis, antioxidant enzyme status and in vivo hydrogen peroxide (H2O2) production in rats with chronic renal failure caused by 5/6 nephrectomy (remnant kidney) and compared results to data obtained with propranolol, a beta-blocking drug without scavenging characteristics. Carvedilol and propranolol were administered during 11 weeks following reduction of nephron number. Kidneys were examined using enzymatic and histological techniques. Both carvedilol and propranolol decreased systolic blood pressure. Compared to propranolol, carvedilol offered some additional beneficial effects on renal function, particularly with regard to glomerulosclerosis. Lipid peroxidation, evaluated by malonaldehyde and 4-hydroxynonenal concentration in cortex homogenates, was decreased in carvedilol-treated rats only. Superior beneficial effect of carvedilol treatment is not linked to a significant up-regulation of the activities of the remnant kidney antioxidant enzymes (catalase, glutathione peroxidase and superoxide dismutase) or to a decreased in vivo H2O2 production.

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.

In 44 patients with end-stage renal disease, 24 on hemodialysis and 20 on CAPD, the survival was calculated using the life table method. Median survival for CAPD was 19 months and for hemodialysis 47 months. Using Cox's proportional hazards model, treatment modality and performance score were significant determinants of survival. Performance score was influenced by age and kidney disease. When survival was analyzed separately for patients with a good or a bad performance score, the survival was better in the hemodialysis group only in patients with a bad score (ECOG 3 and 4). Patients with a good score had similar prognoses, irrespective of treatment modality.

The pharmacokinetics of a single 2 mg IV dose of chlordesmethyldiazepam has been studied in 11 patients with renal failure on regular haemodialysis and in 11 age-matched healthy controls. The kinetics was also examined after a single 2 mg oral dose in 6 of the 11 renal failure patients. After intravenous administration the kinetics of total chlordesmethyldiazepam in renal patients and controls were the same. The unbound fraction of the drug in renal patients was higher (5.5%) than in controls (2.9%). Correction for differences in protein binding revealed a reduced apparent volume of distribution (47 vs. 140 l.kg-1) and a reduced clearance (5.0 vs. 10.5 ml.min-1.kg-1) in the patients. The systemic availability of oral chlordesmethyldiazepam was good (82%) despite a relatively slow absorption rate.

In normal man 1, 25 (OH)2-vitamin D3 [1, 25 (OH)2D] increases both basal and TRH-stimulated prolactinemia; this effect is completely reversible by the calcium antagonist nifedipine. Similarly the 1, 25 (OH)2D-induced hypercalcemia is totally inhibited by nifedipine. These findings suggest that both biological effects of 1, 25 (OH)2D are mediated by calcium-dependent mechanisms.

A coaxial dual flow catheter has been tested for thrombapheresis with a continuous flow blood cell separator in order to render the procedure as comfortable as possible for our donors. Therefore, two groups of five donors underwent a standard plateletpheresis: 3500 ml of blood were withdrawn at a speed of 35-45 ml per minute and were anticoagulated with ACD-A in a 1/9 ratio to whole blood. In the first group one vein puncture was effectuated with the coaxial catheter after local anesthesia. Two 14G catheters were used in the second group. In both groups the platelet yield was studied as well as the half life of 111-Indium-oxinate labeled platelets after autologous transfusion. Although the comfort of the donors was greatly improved, the one needle procedure resulted in a mean platelet yield of 1,28.1011 while the two needle procedure yielded 3,46.1011 platelets. In contrast, the survival of the platelets after autologous transfusion did not differ significantly in the two groups: t 1/2 in group I was 3,94 d, in group II 3,66 d. It is advocated that the poor efficacy of the single needle procedure might be due to recirculation.

Pooled serum and the serum of a healthy volunteer were spiked with aluminum and aluminum species were separated on Bio-gel columns. With the P10 column, less than 40% of the aluminum was eluted with the high-molecular-weight (m.w.>20 00) fraction; the total aluminum concentration was 600 μg l −1 . Tw lower m.w. fractions were also recovered. With the P4 column, only one high m.w. (65–100%) and one low m.w. (0–53%) fraction were recovered; the total Al concentrations was 10–110 μg l −1 . When a hemofiltrate obtained from uremic patients on regular hemofiltration and spiked with 60–110 μg Al l −1 was applied to the P4 gel, two lower m.w. fractions were detected. The adsorption/desorption of “free” aluminum on the column was studied with 0.9% NaCl solution, Earle's medium and filtrate. Normal column fractionation and frontal analysis (adsorption and desorption breakthrough curves) were used. Redistribution of aluminum seemed not to occur within the serum when in contact with the column, but contamination from extraneous aluminum could greatly alter the aluminum distribution. Different sources of errors were identified.8

Basal plasma prolactin (PRL) has been measured in 6 patients with chronic renal failure 3 months before and at monthly intervals during a 3 months 1,25-dihydroxyvitamin D3 [1,25 (OH)2-D] treatment. Plasma PRL decreased rapidly during, 1,25 (OH)2-D treatment, while it remained unchanged during the 3-months control period. There was no correlation between PRL and parathyroid hormone (PTH; measured either with carboxy- or amino-terminal assays) and several other parameters. A direct effect of 1,25 (OH)2-D on PRL secretion may exist.

Plasma immunoreactive parathyroid hormone level, urinary excretion of adenosine cyclic 3′,5′-monophosphate (cyclic AMP) and the sensitivity of the renal tubule to calcium infusion and to parathyroid extract were investigated in a patient with nonfamilial hypophosphatemic osteomalacia. Plasma immunoreactive parathyroid hormone concentration was normal and basal urinary excretion of cyclic AMP was increased. Renal cortical adenylate cyclase, as measured by urinary cyclic AMP excretion, was certainly as sensitive to exogenous parathyroid extract as in normal subjects. After a previous calcium infusion, a greater parathyroid-hormone-sensitive component of phosphorus transport in the kidney was present than in two control subjects. Our results indicate that in nonfamilial hypophosphatemic osteomalacia the renal tubule could be hyperresponsive to parathyroid hormone. © 1980 Springer-Verlag., SCOPUS: ar.j, info:eu-repo/semantics/published

In developing this method for determination of Al in bone we paid special attention to the homogenization of bone samples, which presents great difficulties for trace-element analysis. To minimize the risk of contamination, we preferred low-temperature ashing over classical wet-digestion techniques for destruction of the organic material. Graphite-furnace atomic absorption spectroscopy is used for measurement of Al. For Al concentrations exceeding 15 micrograms/g, direct standardization against a calibration line can be used (between-run CV, 5.9%). For Al concentrations within the normal range (less than 15 micrograms/g) the standard-addition technique should be applied. Comparison of results by the method with those by a procedure based on extraction of Al with a saturated solution of EDTA revealed that, although the latter method gave considerably lower results for three of 13 samples, there was no statistical difference between results by the two methods.

The acute and long-term efficacy, tolerance and safety of two orally active angiotensin converting enzyme (ACE) inhibitors, captopril (C) and enalapril (E) were compared in patients on regular haemodialysis (RHD). C and E were successively administered for 6 months to 8 RHD patients with hypertension unresponsive to fluid withdrawal and conventional antihypertensive therapy. The fall in blood pressure after a starting dose of 25 mg C or 5 mg E was of the same magnitude. It was not correlated with the initial PRA levels, which were normal in all patients. The mean daily dose of ACE inhibitor was 45 +/- 28 mg during the C period and 19.4 +/- 17.6 mg at the end of the E period. Three patients required additional treatment, comprising beta-blockers and/or calcium antagonists. The individual daily dose of ACE inhibitor, the need for additional treatment and the antihypertensive response achieved were highly correlated during both study periods. During C administration 4 out of 8 patients presented a taste disturbance, which disappeared 2 weeks after substituting E for C. Serum electrolytes, liver enzymes, haemoglobin concentration and white cell and platelet counts remained unchanged throughout both study periods. It is concluded that RHD patients with hypertension are responsive to ACE inhibitors, C and E being equally effective.

A 66 year-old woman was referred in 1981 because of renal insufficiency and pronounced nephrocalcinosis. The urinary oxalate excretion was elevated. Secondary hyperoxaluria was excluded. End-stage renal disease necessitated hemodialysis from late in 1982 up to her death in 1986, at the age of 71 years. During the course of the disease, an aggressive arthropathy developed in the fingers. Classical signs of oxalosis were found: deposits of calcium oxalate crystals in bone tissue, the pancreas, myocardium, subcutaneous tissue and especially in the kidneys. This rare case documents the possible occurrence of late clinical presentation and long survival in primary oxalosis.

The effect of 100 ng 1 alpha-OH vitamin D/week alone and in combination with desferrioxamine (DFO), 150 mg/week, was evaluated in aluminum loaded uremic rats. Vitamin D (Vit D) caused an increase of Al in muscle and a decrease in serum Al. Bone histology showed mineralization defect and an increase in bone mass, due to an increase in unmineralized bone, induced both by Al and Vit D administration. Treatment with DFO enhanced urinary Al excretion and lowered tissue Al, without inducing major changes of static bone histology. It is concluded that in Al-loaded uremic rats Vit D can redistribute body Al and that both Al and Vit D can cause a mineralization defect. A 6-week treatment with DFO lowers tissue Al without changing significantly static bone parameters.

Vancomycin is widely used for the treatment of infections with Gram-positive bacteria in patients with end-stage renal disease. The concentration of vancomycin in serum, in ultrafiltrate, and in dialysate was measured during nine haemofiltration and seven haemodialysis procedures with high-permeability membranes. The t1/2 of vancomycin was 101 +/- 19 h in the interdialytic and interhaemofiltration period. There was no significant difference between the haemodialysis clearance (55.2 +/- 18.5 ml/min) and the haemofiltration clearance (66.8 +/- 13.6 ml/min). The redistribution phenomenon was about 25% in the post haemofiltration period and only 10% in the post haemodialysis period. Approximately 270 mg of vancomycin was recovered in dialysate or ultrafiltrate. With high-permeability membranes more commonly used in patients with end-stage renal disease, continuous monitoring of vancomycin therapy is recommended.

As microcytic anemia is a feature of aluminium intoxication, we prospectively studied the hematologic effects of deferoxamine in 10 hemodialysis patients with aluminum-induced bone disease. Comparing the mean monthly results of a 4 month period before and during deferoxamine therapy, we observed an important decrease of the transfusion needs (alpha less than 0.025) and an increase of hematocrit (p less than 0.02), hemoglobin (p less than 0.02), MCV (p less than 0.02) and MCH (p less than 0.05); the number of red blood cells remained unchanged. Our results show that deferoxamine treatment of dialysis patients with aluminum bone disease can markedly improve their anemia, even in the absence of recent aggravation, microcytosis and hypochromia. They also suggest that aluminum could participate in the anemia of dialysis patients even if it is normocytic.

Torasemide is a new loop diuretic with a linear dose response curve after administration of doses between 2.5 and 80 mg in subjects with normal renal function (1). In the present study, patients with advanced renal failure were studied because pharmacokinetics of potent diuretics are different under these conditions.

Aluminum (Al) intoxication is a condition that reponds well to treatment with desferrioxamine (DFO) in humans with renal failure. The present study deals with the effect of DFO administration on the Al concentrations of different tissues and on bone histology in rats with renal failure, loaded with Al. After the Al-loading there is an important increase of Al in serum, (1,103 +/- 355 micrograms/l) (mean +/- SD), bone (116 +/- 14 mg/kg), liver 238 +/- 78 mg/kg) and muscle (8.5 +/- 4.1 mg/kg). Urinary Al excretion averages 287 +/- 68 micrograms/d. Serum biochemistry reveals renal failure and hypercalcemia (3.5 +/- 0.3 mmol/l). The rats were subsequently treated by either placebo or 150 mg DFO per week. The placebo-treated rats show a spontaneous decrease of serum Ca and Al and of liver and muscle Al content. The DFO-treated rats had, compared to the placebo-treated animals, an increase of urinary Al excretion and lower Al concentration in bone and brain. Bone histology after Al-loading shows an increase in osteoid measurement when compared with non-Al-loaded animals with renal failure: osteoid volume 25.6 +/- 13.3% versus 5.0 +/- 2.9% and osteoid index 63.6 +/- 22.1% versus 27.3 +/- 15.3% in Al-loaded and non-Al-loaded animals, respectively. In addition, the aluminon stain covered 89.7 +/- 3.8% of the bone trabeculae of Al-loaded rats. Under placebo treatment the osteoid measurements increase, reflecting a worsening of Al-induced bone disease. DFO therapy did not result in a significant change of the different measurements of bone histology, despite the decrease of aluminon staining to 67.7 +/- 13.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

A coaxial dual flow catheter has been tested for thrombapheresis with a continuous flow blood cell separator in order to render the procedure as comfortable as possible for our donors. Therefore, two groups of five donors underwent a standard plateletpheresis: 3500 ml of blood were withdrawn at a speed of 35-45 ml per minute and were anticoagulated with ACD-A in a 1/9 ratio to whole blood. In the first group one vein puncture was effectuated with the coaxial catheter after local anesthesia. Two 14G catheters were used in the second group. In both groups the platelet yield was studied as well as the half life of 111-Indium-oxinate labeled platelets after autologous transfusion. Although the comfort of the donors was greatly improved, the one needle procedure resulted in a mean platelet yield of 1,28.10 while the two needle procedure yielded 3,46.10 platelets. In contrast, the survival of the platelets after autologous transfusion did not differ significantly in the two groups: t 1/2 in group I was 3,94 d, in group II 3,66 d. It is advocated that the poor efficacy of the single needle procedure might be due to recirculation.

Chlordesmethyldiazepam (CDDZ) is a 1, 4-benzodiazepine. Farmacokinetic data in humans after single- and multiple-dose oral and intravenous administration showed a long half-life, extensive biotransformation and low clearance (1). Only one brief report (2) shows that diazepam has shorter half-life and higher clearance in patients with renal failure. It seemed therefore worthwhile to study in patients with renal failure the pharmacokinetics of CDDZ both after intravenous and oral administration.