Biomedical subjects

H Thysell

Publications and source records attributed to H Thysell.

At least 37 records · Page 2Linked to original sources

PubMed1996

Analysis of proteinuria: reference limits for urine excretion of albumin, protein HC, immunoglobulin G, kappa- and lambda-immunoreactivity, orosomucoid and alpha 1-antitrypsin.

Efficient use of assessment of urine protein excretion in nephrological practice requires adequate reference intervals. To determine the upper reference limits of urine albumin, protein HC (alpha 1-microglobulin, immunoglobulin G (IgG), orosomucoid (alpha 1-acid glycoprotein, alpha 1-antitrypsin, and kappa- and lambda-chain immunoreactivities, the concentrations of these proteins were measured in urine samples from 95 healthy, adult individuals, using rapid, generally available methods and with conditions for urine collection which secured stable protein levels. The obtained values were expressed in mg 1(-1), as the urine protein-creatinine index and as fractional protein-creatinine clearance. No differences were found between the upper reference limits in the first voided morning urine samples and the randomly collected urine samples, nor between the upper reference limits in urine samples collected from males and females. The urinary excretion of the tested proteins did not correlate to age, positive dipsticks for haematuria nor to granular casts in urine sediment. Thus, the same upper reference limits can be used for both sexes and regardless of the type of urine collection. The upper reference limits of urine protein-creatinine index found in this study were: for albumin, 3.8 mg mmol(-1); for protein HC, 0.7 mg mmol; for IgG, 0.8 mg mmol(-1); for orosomucoid, 0.7 mg mmol(-1); for alpha 1-antitrypsin, 0.2 mg mmol(-1), and for kappa-immunoreactivity 0.7 mg mmol(-1). The upper reference limit for lambda-immunoreactivity was below the detection limit.

Adult↗

PubMed1996

C4 phenotypes in IgA nephropathy: disease progression associated with C4A deficiency but not with C4 isotype concentrations.

IgA nephropathy (IgAN) is a common glomerular disease and is thought to have an immunological origin which may involve complement-mediated pathogenic mechanisms. We performed C4 phenotyping and C4 isotype quantification in 93 IgAN patients in Southern Sweden. Phenotype frequencies did not deviate from those of healthy controls. However, three patients had homozygous C4A deficiency and these all belonged to a group of fifteen patients with end-stage renal failure (p < 0.0035). Progression to end-stage renal failure did not appear to be faster than in other IgAN patients. Both C4A and C4B concentrations were raised in the IgAN patients, but the C4A/C4B concentration ratios did not deviate from those of healthy controls. This indicated that heterozygosity for C4A or C4B deficiency or other reasons for the relatively low concentrations of the protein were not associated with disease susceptibility. There was no correlation between low C4A/C4B ratio and poor prognosis. In conclusion, the findings suggested that homozygous C4A deficiency predisposes to development of end-stage renal failure. The question if this is due to complement dysfunction or to linked genetic factors remains to be elucidated.

Adolescent↗

PubMed1995

The effect of dialysis on radiocaesium in man.

Dialysis is used for cleaning the blood in patients with end-stage renal disease. The most common methods are hemodialysis (HD) and peritoneal dialysis (PD). Dialysis patients might constitute a critical group because of poor elimination of radioactive elements ingested. On the other hand dialysis may be a useful decontamination method for radioactivity. The effect of dialysis on the turnover of radiocaesium was studied in 10 HD patients and 4 PD patients. The dialysis fluid, which contains electrolytes and the metabolic waste products, was analyzed for radiocaesium. In this connection the patients were whole-body counted for radiocaesium and 40K. The results show that HD patients generally have a lower body burden of radiocaesium than normal subjects, while PD patients show normal levels. At steady state both dialysis methods eliminate slightly less radiocaesium than normal kidneys do, but in the case of HD during a much shorter time. The calculated effective half-life for radiocaesium was normal in the HD patients, and somewhat longer in the PD patients. Considering that HD is performed only for 12-15 h weekly, the elimination rate of radiocaesium by HD is much higher compared with that by normal kidneys. Thus, HD might constitute an important method for decontamination of radiocaesium after accidental internal contamination.

Body Burden↗

PubMed1995

Hepatitis C superinfection in hepatitis C virus (HCV)-infected patients transplanted with an HCV-infected kidney.

Hepatitis C virus (HCV) genotypes, determined by polymerase chain reaction with type-specific primers, were studied in 5 already HCV-infected patients receiving kidneys from HCV-infected cadaver donors. Three patients were investigated retrospectively using stored pre- and posttransplantation sera and followed 18-28 months after transplantation. Two recipients with HCV genotype 2b infection had received kidneys from 1 genotype 3a-infected donor. In 1 recipient, HCV 2b was replaced by the donor's type; in the other recipient, a prolonged mixed infection of 3a and 2b occurred. Persistent alanine aminotransferase (ALT) elevation (3- to 5-fold) appeared in both patients. The third patient, also HCV 2b infected when transplanted with an HCV 3a-infected kidney, remained infected with HCV 2b only. Two patients, one with HCV genotype 1b and the other with genotype 3a, were followed prospectively with frequent bleeds (initially biweekly) and genotyping over 14 months after they had received kidneys from 1 HCV genotype 1a-infected donor. The HCV 1b-infected recipient remained infected with 1b only and had minimal biochemical signs of liver injury. In the other recipient, mixed infection of 3a and 1a appeared at week 3 and persisted for several weeks, until only genotype 1a could be detected. This patient had elevated ALT levels before transplantation. After onset of mixed infection, ALT levels increased further for several weeks, and returned to pretransplantation levels when only HCV 1a was found. HCV-infected kidneys transplanted into HCV-infected recipients gave 3 different virus patterns. Most patients benefitted in the short term, but some super-infected patients experienced increased liver damage.

Adult↗

PubMed1995

Cytokines in childhood hemolytic uremic syndrome and thrombotic thrombocytopenic purpura.

Serum and urine cytokines were analyzed in children with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Interleukin-6 (IL-6) was elevated in the serum of 33 of 35 children with HUS (94%) and in 2 of 2 children with recurrent TTP. Serum IL-6 was higher in children with HUS who developed anuria, extrarenal manifestations during the acute phase of illness and/or chronic renal sequelae. Tumor necrosis factor-alpha (TNF-alpha) was detected in the serum of 7 patients with HUS (20%) and 1 patient with TTP. IL-6 and TNF-alpha were elevated in the urine of 4 of 4 children with HUS and 2 of 2 children with TTP. Urinary levels were higher than serum levels, suggesting local production of cytokines in the urinary tract. Sequential serum and urine samples showed that IL-6 levels varied with disease activity. IL-6 and TNF-alpha were not detected in the serum (n = 25) and urine (n = 15) of healthy children. We conclude that IL-6 in urine may be used to monitor disease activity in HUS and TTP.

Adolescent↗

PubMed1995

Circulating neuropeptide Y in plasma from uremic patients consists of multiple peptide fragments.

Increased plasma levels of neuropeptide Y (NPY)-like immunoreactivity (p-NPY-LI) have been described in hemodialysis (HD) patients. In this investigation the effect of a standard HD on p-NPY-LI, analyzed by radioimmunoassay and reverse-phase high performance liquid chromatography (HPLC), was studied. During dialysis p-NPY-LI increased from 128 +/- 5 to 154 +/- 8 pmol/l (p < 0.01). The change in p-NPY-LI during the treatment correlated with the ultrafiltration volume (rs = +0.72, p < 0.05). The HPLC separation revealed a complex pattern of NPY-immunoreactive peptides. This was true of the plasma of the control subjects as well as of the uremic plasma. In the case of the controls and the HD patients prior to dialysis, the amount of NPY-LI was rather small. After the dialysis qualitative as well as quantitative changes of the chromatogram were found. Some of the peaks seemed to have a retention time similar to that of the known fragments of synthetic human NPY used as markers. In conclusion, an increase in p-NPY-LI occurred during the dialysis, probably due to fluid removal. The increased level of NPY-LI in uremic plasma represents a mixture of different NPY fragments.

Aged↗

PubMed1995

Evidence that reduced lipoprotein lipase activity is not a primary pathogenetic factor for hypertriglyceridemia in renal failure.

The aim of the study was to document postheparin plasma lipoprotein lipase (LPL) and hepatic lipase activities and relate these to serum lipid, lipoprotein and apolipoprotein concentrations in 85 patients with kidney function ranging from normal to dialysis dependency. Strict selection criteria were applied in order to exclude conditions other than renal failure which may influence lipid metabolism. Stress was laid on minimizing proteinuria and inflammatory activity. The changes in the lipoprotein pattern were numerically strikingly modest compared to those previously reported. This probably reflected the intention to elucidate the contribution of reduced renal function as such to the dyslipoproteinemia of renal failure, a condition often associated with confounding factors. Significant increases in serum concentrations of triglycerides and apolipoprotein CIII were already observed in moderate renal failure, whereas serum concentrations of high density lipoprotein cholesterol and plasma LPL activities were decreased only in severe renal failure. Plasma LPL activities were not significantly reduced in hemodialysis patients (probably due to anticoagulation with low molecular weight heparin), but serum concentrations of triglycerides and apolipoprotein CIII were significantly increased. A multiple regression analysis, taking glomerular filtration rate, LPL and apolipoprotein CIII into account, showed that both plasma LPL activity and serum apolipoprotein CIII concentration independently predicted serum triglyceride concentration. However, serum apolipoprotein CIII concentration was a much stronger predictor than plasma LPL activity. Thus, a decrease in LPL activity does not seem to be a prerequisite for the hypertriglyceridemia of uremia, but it probably accentuates this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Dose regimen adjustment for milrinone in congestive heart failure patients with moderate and severe renal failure.

This study was designed to test a proposed dose modification for intravenous milrinone in congestive heart failure patients (CHF, NYHA I-II) with either moderate or severe renal impairment. All the patients were administered an intravenous loading dose of drug at 50 micrograms kg-1 over 10 min. This was followed by an 18 h maintenance infusion of milrinone at 0.45 or 0.35 micrograms kg-1 min-1 for the moderate (chromium-EDTA clearance of 31-75 mL min-1, n = 10) and severe renally impaired subjects (chromium-EDTA of clearance 10-30 mL min-1, n = 11), respectively. Plasma and urine samples were collected for up to 34 h and analysed for parent drug by validated HPLC methods. The mean (+/- s.d.) steady-state plasma concentrations of milrinone were within the therapeutic range (100-300 ng mL-1) for both groups, with values of 239 +/- 71 ng mL-1 and 269 +/- 32 ng mL-1 for the moderate and severe patients, respectively. No statistical differences were observed between the steady-state values for the two groups. With the exception of two patients per group, individual steady-state levels were also within the therapeutic range. Those outside the nominal range showed steady-state levels, ranging between 308 and 353 ng mL-1, that were not associated with any serious adverse events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Elevated plasma levels of acute phase proteins in mesangioproliferative glomerulonephritis, membranous nephropathy and IgA nephropathy.

In order to study the possible role of active inflammatory processes in clinical indolent primary chronic glomerulonephritides, plasma concentrations of the acute phase proteins: alpha 1-antitrypsin, haptoglobin, orosomucoid and C-reactive protein were measured in 166 glomerulonephritis patients. The patients had a diagnosis of either mesangioproliferative glomerulonephritis, membranous nephropathy or immunoglobulin A nephropathy and were divided in two groups, one with heavy urinary albumin losses and one with moderate to slight urinary albumin excretion. The median plasma concentration values for alpha 1-antitrypsin, haptoglobin and orosomucoid were increased in all three kinds of the investigated glomerulonephritides with exception for orosomucoid in patients with heavy urinary albumin losses and in the membranous nephropathy group. The plasma concentration values for C-reactive protein were not elevated at all in the material. The increase of plasma levels of acute phase proteins could be the result of persistent inflammatory stimuli that occur in primary chronic glomerulonephritides. The finding of unchanging plasma levels of C-reactive protein in contrast to increased concentrations of the other acute phase proteins could be of significance in diagnosing infections or other inflammatory diseases in patients with chronic glomerulonephritis.

Acute-Phase Proteins↗

PubMed1994

Stability of albumin, protein HC, immunoglobulin G, kappa- and lambda-chain immunoreactivity, orosomucoid and alpha 1-antitrypsin in urine stored at various conditions.

Urine samples from 10 randomly selected patients with advanced renal disease were each divided into six aliquots and a preservative solution containing benzamidinium chloride, EDTA, tris(hydroxymethyl)-aminomethane and azide was then added to three of the aliquots. Aliquots with and without additive were then stored at room temperature for up to 7 days, at 4 degrees C for up to 30 days and at -20 degrees C for up to 6 months. The concentrations of albumin, protein HC, IgG, orosomucoid and alpha 1-antitrypsin as well as the kappa- and lambda-chain immunoreactivities in the samples were determined by automated immunoturbidimetry or by single radial immunodiffusion after 1, 3, 7, 14, 30, 90 and 180 days of storage. All investigated proteins, except alpha 1-antitrypsin in native urine, were stable for 7 days in the samples stored at room temperature both in the presence and absence of additives. All investigated proteins, except alpha 1-antitrypsin in native urine, were stable for 30 days in the samples stored at 4 degrees C both in the presence and absence of additives. A more complex pattern was observed for the stability of the proteins in the frozen samples. The IgG level decreased rapidly in several samples stored without additives but not in samples stored with additives. The alpha 1-antitrypsin concentration decreased rapidly to about 50% of the initial value in several samples stored both with and without additives. The rate of the decrease for both the IgG and the alpha 1-antitrypsin level varied between samples and the main decrease for several samples was seemingly caused by the freezing and/or thawing per se and not by the storage period in between.

Albuminuria↗

PubMed1994

Effect of erythropoietin on muscle metabolic rate, as measured by direct microcalorimetry, and ATP in hemodialysis patients.

Ten anemic hemodialysis patients were treated for 6-14 months with human recombinant erythropoietin (EPO). The mean hemoglobin level significantly increased by 42%. Pretreatment skeletal muscle heat production rate at rest, as determined by direct microcalorimetry, was lower than normal (p < 0.03), indicating decreased metabolic activity. ATP levels in muscle were inversely correlated (rs = -0.66, p < 0.05) with the heat production values. The latter significantly increased by about 40% and were almost normalized by the therapy, whereas a decline in the mean ATP level was seen, from 14.8 to 13.2 mumol g-1 of muscle (p = 0.06). We hypothesize that the lowered ATP concentration in muscle after treatment might have been due to an enhanced ATP consumption in parallel with improved muscle strength. Alternatively, since acidosis prior to treatment might have altered the equilibrium state of the creatine kinase reaction towards ATP production, it is possible that the improved oxygenation after EPO had increased pH in the muscle and catalyzed the transfer of phosphate from ATP to PCr. It is concluded that EPO treatment can almost normalize the decreased muscle metabolic rate in hemodialysis patients, and that the anemia per se seems to be an important cause of the deranged metabolism in striated muscle.

Adenosine Triphosphate↗

PubMed1994

Low-dose simvastatin is a well-tolerated and efficacious cholesterol-lowering agent in ciclosporin-treated kidney transplant recipients: double-blind, randomized, placebo-controlled study in 40 patients.

The high prevalence of hypercholesterolemia in kidney transplant recipients probably contributes to the high cardiovascular mortality in these patients. Except for diet, there is no generally recommended cholesterol-lowering treatment. We conducted a double-blind, randomized, placebo-controlled study with low-dose simvastatin in 40 ciclosporin (CS)-treated kidney transplant recipients during 16 weeks, focusing on side effects and dose finding. In the simvastatin group, the mean serum total and LDL cholesterol concentrations decreased by 23 and 33%, respectively, and the mean serum HDL cholesterol concentration increased by 12%, after 4 weeks of treatment with simvastatin 10 mg daily. Increasing the dose to 20 mg daily in a few patients only resulted in marginal further reductions of the serum cholesterol concentrations at the expense of doubling the plasma simvastatin 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity concentrations. The differences between the changes in the serum cholesterol concentrations in the simvastatin group and the negligible changes in the placebo group were statistically significant. There was no case of proximal myopathy and the serum creatine kinase concentrations did not differ between treatment groups. In conclusion, low-dose simvastatin appears to be a well tolerated and efficacious cholesterol-lowering treatment in CS-treated kidney transplant recipients. Simvastatin 10 mg daily seems to be the most suitable dose for the majority of these patients.

Adult↗

PubMed1994

Delayed decrease in plasma levels of atrial natriuretic peptide during cold hemodialysis.

The high plasma levels of the vasodilating hormone atrial natriuretic peptide (alpha-ANP), observed in patients with chronic renal failure, decrease substantially during hemodialysis (HD), probably owing to volume reduction. Cardiovascular stability is better maintained by the use of cold dialysate although underlying mechanisms are unknown. In order to investigate the effects of different dialysate temperatures on hemodynamic stability and plasma levels of immunoreactive ANP (p-irANP), 10 stable HD patients were dialyzed with bicarbonate dialysis fluid for 240 min with each of 3 different dialysate temperatures: 36.5 degrees C (normal HD; NHD), 38.5 degrees C (warm HD; WHD) and 34.5 degrees C (cold HD; CHD). A Cuprophan plate dialyzer was used. The ultrafiltration volume and ultrafiltration rate were identical in each patient during the treatments. p-irANP was determined by radioimmunoassay, using 2 antisera which different cross-reactivity to ANP-related peptides. During NHD a nonsignificant decrease in mean arterial blood pressure from 111 +/- 5 to 103 +/- 8 mm Hg was observed. A significant (p < 0.05) decrease in mean arterial blood pressure from 109 +/- 4 to 96 +/- 6 mm Hg occurred during WHD, while during CHD it remained stable (111 +/- 4 before, 112 +/- 5 mm Hg after). Irrespective of the dialysate temperature or the antiserum used, p-irANP decreased significantly (p < 0.05) during the treatment. The reduction in p-irANP was delayed during CHD, the decrease being significantly (p < 0.05) less pronounced after 120 min. At the end of the treatment no significant difference was observed between the regimes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Occurrence of autoantibodies directed against myeloperoxidase and elastase in patients treated with hydralazine and presenting with glomerulonephritis.

We have undertaken an investigation retrospectively of 21 patients with positive antinuclear antibodies, who had been on hydralazine treatment and developed a glomerulonephritis. Four patients had circulating antimyeloperoxidase (MPO) and two of them were concluded to have a hydralazine-induced glomerulonephritis, corresponding to a frequency of 10%. These two patients had antibodies of IgG and IgM class directed against myeloperoxidase (MPO), and also antibodies against elastase. These two patients had also a biopsy proven extracapillary glomerulonephritis with focal segmental necrosis. Antibodies against elastase were furthermore seen in three patients with proliferative glomerulonephritis and in one patient with membranoproliferative glomerulonephritis. This study confirms an association between circulating anti-MPO and a histopathological picture compatible with extracapillary proliferation and focal segmental necrosis. From a clinical, histopathological and serological point of view it can be concluded that in two patients the glomerulonephritis was associated with antibody evidence of an autoimmune side effect.

Adult↗

PubMed1994

Changes in plasma levels of vasoactive substances during routine acetate and bicarbonate hemodialysis.

Hemodynamic stability is better preserved during bicarbonate hemodialysis compared to acetate. We have studied the effects of bicarbonate (HDB) and acetate hemodialysis (HDA) on plasma levels of vasoactive substances. The treatments were performed for 270 min. A cuprophan plate dialyzer was used. The ultrafiltration volume and the ultrafiltration rate were identical in the individual patients during the two treatments. In the case of vasoconstrictors there was an increase in neuropeptide Y (NPY) (20%, p < 0.01) during HDB and arginine vasopressin (AVP) was unchanged. Unlike this was the response during HDA when there was no change in NPY and a decrease in AVP (38%, p < 0.01). An increase in noradrenaline (NA) (41%, p < 0.05) occurred during HDA different from what was the case during HDB. There was a gradual increase in renin (PRA) during both HDB (141%, p < 0.05) and HDA (148%, p < 0.01). With respect to vasodilators there were no differences between the two regimes regarding calcitonin gene-related peptide (CGRP) and motilin (MOT). The change in substance P (SP) during the treatments was also similar but somewhat more pronounced during HDB. Thus, an initial rise occurred (HDB, 81%, p < 0.01; HDA, 36%, p < 0.05) followed by a decrease (HDB, 26%, p < 0.05) or a tendency to decrease (HDA, 12%, p = 0.058) during the remaining part of the treatment. A rise in beta-endorphin (beta-END) occurred during HDB (10%, p < 0.05) but not during HDA. An increase in vasoactive intestinal peptide (VIP) occurred during HDB (27%, p < 0.05) different from the decrease during HDA (11%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

PubMed1993

Changes in plasma levels of vasoactive peptides during standard bicarbonate hemodialysis.

During bicarbonate hemodialysis, there is an increase in peripheral vascular resistance of nonadrenergic origin, counteracting the hypotensive effect of fluid removal during the course of the dialysis. In this study, the plasma levels of vasoactive regulatory peptides, noradrenaline and renin, were investigated in 11 patients with chronic renal failure during standard bicarbonate hemodialysis (STHD) for 270 min. As regards vasoconstrictors, an increase in gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY) and plasma renin activity (PRA) occurred. However, arginine vasopressin and noradrenaline were unchanged. With respect to vasodilators, calcitonin gene-related peptide was not changed. An initial increase in beta-endorphin (beta-END) occurred, followed by a decrease during the remaining part of the treatment. Motilin decreased during the first part of the treatment but increased to the baseline level during the latter part. An increase in substance P was observed while vasoactive intestinal peptide decreased. We conclude that an increase in vasoconstricting substances (gamma 2-MSH, NPY, PRA) occurs during STHD, probably owing to the decrease in plasma volume. With the exception of beta-END, the changes in vasodilators were fairly small. The data suggest that vasoactive substances might participate in the hemodynamic response to hemodialysis.

Adult↗

PubMed1993

Changes in plasma levels of vasoactive peptides during sequential bicarbonate hemodialysis.

The hemodynamic response to isolated ultrafiltration (IUF) is characterized by a vasoconstriction, while there is no significant change in peripheral vascular resistance during isovolemic bicarbonate hemodialysis (IVHD). The present investigation was designed to study the plasma levels of vasoactive regulatory peptides together with noradrenaline (NA) and plasma renin activity (PRA) in 11 patients during sequential hemodialysis (SQHD) - IUF for 60 min, followed by IVHD for 210 min. During IUF, the vasoconstrictors arginine vasopressin (AVP), gamma 2-melanocyte-stimulating hormone (gamma 2-MSH), neuropeptide Y (NPY), NA and PRA increased. During IVHD, NPY and PRA remained unchanged on a higher level. A decrease in AVP below the baseline and in gamma 2-MSH and NA to the baseline levels occurred during IVHD. In the case of vasodilators, there were no changes in calcitonin gene-related peptide or motilin during SQHD. An increase in beta-endorphin (beta-END) occurred during IUF, followed by a decrease during IVHD. Substance P and vasoactive intestinal peptide were unchanged during IUF but decreased during IVHD. We conclude that SQHD is characterized by an increase in all the measured vasoconstrictors during IUF in response to loss of fluid, and by a decrease in some vasoconstrictors (AVP, gamma 2-MSH, NA) during IVHD. With the exception of beta-END, there were no changes or only minor ones in vasodilators during SQHD. There are changes in plasma levels of vasoactive substances during SQHD but the importance of these changes for the hemodynamic adaptation to ultrafiltration and dialysis needs to be studied further.

Adult↗

PubMed1993

Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin.

A few cases of severe rhabdomyolysis have been reported in heart transplant recipients treated simultaneously with ciclosporin (CS) and the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor lovastatin. When measured, plasma lovastatin HMG-CoA reductase inhibitor concentrations in these patients were higher than expected. This prompted us to study the plasma concentration profiles of simvastatin HMG-CoA reductase inhibitory activity after a single dose of simvastatin in kidney transplant recipients. Five patients treated with CS, azathioprine and prednisolone (CS patients) were compared to 5 patients treated with azathioprine and prednisolone (non-CS patients). The concentration curves had similar shapes but the mean area under the curve/24 h was almost 3 times higher (p = 0.047) and the mean peak concentration was twice as high in CS patients (p = 0.028). These results suggest a difference in the disposition of simvastatin in CS patients as compared to non-CS patients. Simvastatin should be administered in a reduced dosage to CS patients.

Adult↗