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Biomedical subjects

G A Verpooten

Publications and source records attributed to G A Verpooten.

At least 19 recordsLinked to original sources
PubMed1992

Laser microprobe mass spectrometric identification of cyclosporin-induced intrarenal microliths in rat.

Using laser microprobe mass analysis (LAMMA), the composition of 'micro-calcifications (dystrophic type)' or 'metastatic calcifications', previously described in rats given high doses of cyclosporin, have been identified. Female Wistar rats given 12.5, 25 or 50 mg kg-1 per day of cyclosporin in olive oil by gastric gavage developed intrarenal calcifications detected by silver nitrate staining (von Kossa) in the outer medulla after two weeks. The calcifications stained red with periodic acid-Schiff reagent and appeared to be intraluminal microliths with concentric laminations. They could be identified by LAMMA as calcium phosphate (hydroxyapatite), indistinguishable from undecalcified bone. These studies indicate that intraluminal obstruction by calcium phosphate microliths, similar to that seen with magnesium depletion or high phosphate diets, may contribute to renal damage in rats given high-dose cyclosporin. LAMMA appears to be an appropriate technique for identifying both the elemental and organic moieities of intrarenal calcium deposits.

Administration, Oral↗
PubMed1992

Pharmacokinetics of aluminoxamine and ferrioxamine and dose finding of desferrioxamine in haemodialysis patients.

We investigated the pharmacokinetics of desferrioxamine and its chelated compounds aluminoxamine and ferrioxamine in normal volunteers and haemodialysis patients with and without iron overload. Desferrioxamine was administered in a single dose of 30 mg per kg body-weight was a 30-min infusion to five healthy volunteers and to 20 haemodialysis patients (five patients without haemosiderosis and 15 patients with haemosiderosis). The interdialytic half-life of ferrioxamine was 2.2 h in normal volunteers, 13.3 h in dialysis patients without haemosiderosis, and 24.6 h in patients with haemosiderosis. There was no interdialytic elimination of aluminoxamine. In a second study, seven dialysis patients received 5, 10, and 20 mg per kg body-weight desferrioxamine in a random order with a time interval of 2 weeks. The peak serum concentrations after these doses were 4.1 +/- 2.9, 6.4 +/- 2.9, and 10.7 +/- 7.1 mumol/l for ferrioxamine and 2.8 +/- 1.5, 3.1 +/- 1.5, and 4.2 +/- 1.7 mumol/l for aluminoxamine. Thus, a 4-fold increase in desferrioxamine dosage resulted in a 2.7-fold increase in peak ferrioxamine levels and in only a 1.5-fold increase in peak aluminoxamine levels. We conclude that dialysis patients, especially those with haemosiderosis, are exposed to persistently elevated ferrioxamine levels. Weekly doses of 5-10 mg/kg of desferrioxamine would be sufficient for aluminium chelation therapy.

Adult↗
PubMed1991

Influence of dosage schedule on renal cortical accumulation of amikacin and tobramycin in man.

The pathogenesis of aminoglycoside nephrotoxicity is directly related to the accumulation of drug within the renal cortex. To identify measures that might prevent aminoglycoside nephrotoxicity, we investigated the influence of various dosage regimens on the renal cortical accumulation of amikacin and tobramycin in man. Patients undergoing nephrectomy for a renal tumour with normal renal function and no proteinuria received (i) a single dose of either amikacin (15 mg/kg) or tobramycin (4.5 mg/kg) given iv over 30 min, or (ii) a 24-h continuous infusion of either drug or (iii) amikacin as two injections of 7.5 mg/kg or tobramycin as three injections of 1.5 mg/kg over the 24 h preceding nephrectomy. Serum aminoglycoside pharmacokinetics were examined and renal cortical tissue was sampled for drug determination at operation. A single injection yielded cortical concentrations of 115.4 +/- 21.8 and 68.9 +/- 30.3 mg/kg for amikacin and tobramycin, respectively. Tissue levels after continuous infusion were 171.7 +/- 42.9 and 100.0 +/- 30.0 mg/kg for amikacin and tobramycin, respectively. Two injections of 7.5 mg/kg amikacin resulted in renal cortical concentrations of 196.9 +/- 54.9 and three injections of 1.5 mg/kg tobramycin resulted in renal cortical concentration of 76.5 +/- 18 mg/kg. The AUC for the three dosage regimens was not significantly different for the two aminoglycosides indicating linear serum pharmacokinetics for these drugs. In the case of amikacin, a single injection resulted in significantly lower drug levels than did a continuous infusion or administration of the same dose over three injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Amikacin↗
PubMed1991

Single dose pharmacokinetics of perindopril and its metabolites in hypertensive patients with various degrees of renal insufficiency.

1 Perindopril is a prodrug which is hydrolysed in vivo to the active metabolite perindoprilat, an angiotensin-converting enzyme inhibitor. Perindoprilat glucuronide is also found in plasma. 2 The pharmacokinetics of perindopril and its metabolites were studied after administration of a single 4 mg dose to hypertensive patients with various degrees of renal failure. 3 The absorption and elimination of perindopril were not influenced by the degree of renal failure. 4 The mean area under the serum concentration-time curve of the active metabolite perindoprilat increased from 93 ng ml-1 h in subjects with normal renal function to 1106 ng ml-1 in patients with severe renal failure, whereas its half-life varied from 5.0 to 27.4 h. 5 In the same subjects, the mean area under the curve of perindoprilat glucuronide increased from 78 to 513 ng ml-1 h, while its half-life varied from 1.8 h to 7.7 h. 6 Perindopril, perindoprilat, and perindoprilat glucuronide were dialysable. 7 The extent and duration of serum angiotensin-converting enzyme inhibition was augmented in renal failure. The mean area under the inhibition time curve (extrapolated to infinity) increased from 2490%.h in subjects with normal renal function to 42241 %.h in patients with severe renal impairment. The half-life of inhibition varied from 12.1 h to 100.4 h. This effect of renal failure on the pharmacodynamics of perindoprilat was more pronounced than its influence on perindoprilat kinetics. 8 In view of the important influence of renal impairment on the elimination and action of the active substance perindoprilat, a dosage reduction of perindopril is proposed in in patients with renal failure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Legionella pneumophila peritonitis in a kidney transplant patient.

Legionella pneumophila serotype 6 was isolated from the peritoneal fluid of a 59-year-old immunosuppressed patient who developed peritonitis shortly after kidney transplantation. Clinical and radiological examination did not show pulmonary abnormalities until shortly before his death when multiple organ failure developed with adult respiratory distress syndrome (ARDS). Post mortem examination showed L. pneumophila in the peritoneum and in a small pulmonary infiltrate, confirmed by positive cultures. A primary peritoneal inoculation via an indwelling Tenckoff catheter seems to have been the most likely route of infection. Positive L. pneumophila type 6 cultures were obtained from the shower and hot water tap in the room of the patient. L. pneumophila must be considered as a potential cause of peritonitis in which routine microbiological cultures remain negative.

Ascitic Fluid↗
PubMed1990

Acute sodium valproate intoxication: occurrence of renal failure and treatment with haemoperfusion-haemodialysis.

In a child who probably received an overdose of sodium valproate, progressive coma, intermittent tonic-clonic seizures and anuria developed. Laboratory investigations revealed coagulopathy, and anaemia and mildly disturbed liver function. Progressive renal insufficiency, probably due to rhabdomyolysis and myoglobulinuria, occurred later. Treatment consisted of supportive measures, combined haemoperfusion and haemodialysis and IV thiopentone. Clinical and biochemical normalisation was observed after 11 days.

Acute Disease↗
PubMed1989

Once-daily dosing decreases renal accumulation of gentamicin and netilmicin.

The pathogenesis of aminoglycoside nephrotoxicity is intimately related to the extent of drug accumulated in the renal cortex. In the framework of searching for preventive measures of aminoglycoside-induced nephrotoxicity, we investigated the influence of dosage regimen on the renal cortical accumulation of gentamicin and netilmicin in humans. Patients with a tumor partly involving one kidney, with normal renal function, and scheduled for nephrectomy received one dose of either gentamicin (4.5 mg/kg) or netilmicin (5 mg/kg) as a single short-term infusion or as 24-hour continuous infusion. Treatment started 24 hours before surgery. Serum aminoglycoside pharmacokinetics were examined during treatment and renal cortical tissue was sampled at the moment of operation for drug determination. The short-term infusion schedule yielded cortical concentrations of 103.2 +/- 36.3 and 137.4 +/- 34.6 micrograms/gm for gentamicin and netilmicin, respectively. Tissue levels after continuous infusion were 158.1 +/- 52.9 and 178.5 +/- 21.8 micrograms/gm for gentamicin and netilmicin, respectively. For each aminoglycoside, a single short-term infusion resulted in significantly lower renal drug levels than did a continuous infusion of the same dose. From the nephrotoxicity point of view, these data support the administration of gentamicin and netilmicin as once-daily injections. This also supports the appropriateness of further studies to determine clinical efficacy of once-a-day dosing for aminoglycosides.

Drug Administration Schedule↗
PubMed1988

Propylene glycol-induced side effects during intravenous nitroglycerin therapy.

Propylene glycol, an alcohol frequently used as a solvent in medical preparations, is considered non-toxic. We found that this solvent, used in a commercially available IV nitroglycerin solution, may cause hyperosmolality, hemolysis and lactic acidosis. The influence of kidney function as the main determinant in causing accumulation of this solvent and consequently hyperosmolality is emphasized. A review of the literature dealing with propylene glycol is given. The possible mechanisms of neurological disturbances occurring during IV nitroglycerin therapy are discussed.

Acidosis, Lactic↗
PubMed1988

Effect of hyperfiltration, proteinuria and diabetes mellitus on the uptake kinetics of gentamicin in the kidney cortex of rats.

The influence of hyperfiltration-hypertrophy, proteinuria and glucosuria on the renal cortical uptake of gentamicin was studied in several experimental models. Two groups of remnant kidney rats, one fed a standard protein diet and one a low protein diet, heavy proteinuric rats (adriamycin) and diabetic rats, each with their own control group, were treated with increasing doses of gentamicin, given as a continuous infusion over 6 hr. The relationship between increasing steady-state serum levels (ranged from 1 to 100 micrograms/ml) and the cortical gentamicin concentrations at the end of the infusions was examined by means of Michaelis-Menten kinetics. The uptake curves were compared to their respective control curves. It was demonstrated that gentamicin uptake was reduced in remnant kidney rats fed standard diet (showing hyperfiltration and heavy proteinuria), in adriamycin rats (showing heavy proteinuria in the absence of hyperfiltration) and in diabetic rats. Uptake of gentamicin in remnant kidney rats fed low protein diet (showing hyperfiltration and slight proteinuria) was comparable to controls. It appeared that among the pathophysiological factors examined, proteinuria is the most important in decreasing the cortical uptake of gentamicin. It is suggested that high levels of proteins in the proximal tubular fluid interfere with the adsorptive endocytic process, involved in the uptake of both proteins and gentamicin.

Animals↗
PubMed1988

Automated measurement of kidney lysosomes by light microscopy. Influence of cyclosporine treatment.

After staining for acid phosphatase, video images were acquired from 1-micron sections of the kidneys of rats treated with cyclosporine. Automated segmentation of the lysosomes was followed by measurements of their area, number and optical density; tubular area was delineated manually. In addition to small lysosomes, representing more than 80% of the total number, all kidneys contained a second population of larger organelles. Cyclosporine treatment with 50 mg/kg/day for one week and with 25 mg/kg/day for three weeks, but not with 25 mg/kg/day for one week, induced a significant increase of lysosomal area, especially in the larger organelles (+200%). In a few animals, this was accompanied by a reduction in the number of lysosomes, suggesting a fusion of the organelles. Other parameters were not consistently modified by treatment. Cyclosporine treatment also elicited the appearance of fat droplets; however, lysosomes were not enlarged in tubular cells containing fat droplets.

Animals↗
PubMed1987

Functional acute renal failure in a patient with carcinoid syndrome.

Acute renal failure occurred in a patient with a carcinoid syndrome whenever he developed a flushing episode. Renal biopsy performed during one of these oliguric episodes did not reveal any lesions which could explain this reversible form of renal insufficiency. Urinary indices were not conclusive. Alteration of intrarenal hemodynamics by vasoactive compounds is proposed to be the causative mechanism of this relapsing acute oliguric renal failure.

Acute Kidney Injury↗
PubMed1987

Acute oligo-anuria during ovarian hyperstimulation syndrome.

Severe ovarian hyperstimulation developed in a young woman during ovulation induction with human menopausal and chorionic gonadotropins. This was complicated by acute functional renal insufficiency with vascular overfilling and incipient pulmonary edema, possibly caused by indomethacine and fluid treatment. The pathogenetic mechanisms involved are discussed.

Acute Kidney Injury↗
PubMed1986

Choice of drug and dosage regimen. Two important risk factors for aminoglycoside nephrotoxicity.

Since the clinical use of aminoglycosides may be limited by the development of nephrotoxicity, it is important to be aware of those risk factors associated with a greater incidence of renal damage. Some of these factors are related to the drug and its administration and others are related to the patient's clinical condition. In the human kidney, the toxicity mechanism is very likely the same for all aminoglycosides, although the risk of nephrotoxicity increases for a given aminoglycoside as cortical concentrations increase. Kinetic studies in the rat demonstrated a nonlinear increase in renal cortical uptake of gentamicin and netilmicin, a linear relationship for tobramycin uptake, and a mixed kinetic pattern for amikacin, that is, saturation kinetics at low serum concentrations and a linear pattern at high serum levels. At comparable steady-state low serum levels, amikacin and tobramycin showed lower cortical concentrations than gentamicin or netilmicin, demonstrating a lower affinity for the uptake of amikacin and tobramycin in the rat. Since drug uptake kinetics determine the extent of cortical concentrations achieved, dosing strategies may affect cortical accumulation of aminoglycosides. Our kinetic data show that continuous infusions of low doses of gentamicin and amikacin resulted in higher cortical levels, but the differences between regimens were more remarkable for gentamicin than for amikacin. For tobramycin, however, cortical concentrations were similar regardless of the dosing strategy used. In addition, our data show that dosage regimens also determine cortical accumulation in humans. A second major determinant of nephrotoxicity is intrinsic toxicity. At therapeutic doses, gentamicin, tobramycin, netilmicin, and amikacin induce an early lysosomal phospholipidosis in the human kidney cortex comparable to that observed in animals treated with low doses of these drugs. However, animal and human studies have shown that amikacin induces significantly less lysosomal overloading than the other aminoglycosides with no loss of phospholipase A1 activity. Based on the examination of cortical drug levels and the detection of early biochemical and morphologic alterations induced by aminoglycosides, the data suggest that amikacin has less pronounced nephrotoxic effects than gentamicin, netilmicin, or tobramycin, when used in strictly comparable clinical conditions.

Amikacin↗