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Biomedical subjects

T Risler

Publications and source records attributed to T Risler.

At least 73 records · Page 4Linked to original sources
PubMed1994

Pharmacokinetics of torasemide and its metabolites in end-stage renal disease.

The pharmacokinetics of torasemide, a new loop diuretic, as well as its active metabolites M1 and M3, and its inactive main metabolite, M5, were studied in 12 patients with end-stage renal failure during single i.v. (n = 6) or single oral (n = 6) dosing of 200 mg torasemide, and during chronic oral treatment for 9 days (n = 12). The elimination half-life (t1/2) of torasemide was unchanged in renal failure, whereas t1/2 of the torasemide metabolites M1, M3, and M5 were markedly prolonged. However t1/2 as well as the area under the plasma level time curve of torasemide and its metabolites were unchanged during chronic compared to acute administration. The results of this study suggest that despite the increased half-life of torasemide metabolites M1, M3 and M5 in end-stage renal failure patients, no accumulation of the parent drug torasemide and its metabolites during chronic dosing is demonstrable.

Diuretics↗
PubMed1994

Comparative long-term experience with immunoadsorption and dextran sulfate cellulose adsorption for extracorporeal elimination of low-density lipoproteins.

Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to 2 years. The mean plasma volume processed per session to decrease total cholesterol to a target level of 100-150 mg/dl at the end of LDL apheresis was significantly lower in DSA than in IMA: 143% vs. 180% of the individual plasma volume. Both LDL apheresis procedures achieved a mean acute reduction of plasma LDL cholesterol by more than 70%. The average interval concentrations of plasma LDL cholesterol obtained without concomitant lipid-lowering medication were 151 +/- 26 mg/dl compared to 351 +/- 65 mg/dl at baseline in the IMA-treated patients and 139 +/- 18 mg/dl compared to 359 +/- 48 mg/dl at baseline in the DSA-treated patients. Two patients from the DSA group died after 2 years of study participation due to a stroke and a sudden cardiac death several days after the last plasma therapy. Treatment-related side effects were infrequent. Long-term therapy with IMA and DSA was associated with symptomatic improvement of coronary artery disease and mobilization of tissue cholesterol deposits. Analysis of coronary angiograms after 3 years of weekly LDL apheresis with IMA revealed in five patients nearly identical atherosclerotic lesions without definite regression or progression.

Adult↗
PubMed1994

Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application.

Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebo-controlled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-beta-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 +/- 10.6 mumol/liter and 40.1 +/- 10.9 mumol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 +/- 40 to 75 +/- 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 +/- 26 vs. 78 +/- 33 ml/min/1.72 m2).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗
PubMed1994

Comparative pharmacokinetics and pharmacodynamics of loop diuretics in renal failure.

Loop diuretics increase the fractional excretion of volume, sodium, potassium, chloride and calcium in all stages of renal failure, and their potency is directly correlated with these excretory activities. Tubular secretion of loop diuretics in renal failure is impaired both by reduced renal blood flow and by reduced activity of the tubular carrier system. For these reasons, high concentrations of diuretics in the peritubular capillaries are necessary to guarantee delivery of sufficient drug to their site of action in the ascending limb of the loop of Henle. Piretanide and furosemide have a constant extrarenal elimination and thus accumulate in renal failure. Decreased renal excretion of bumetanide is compensated by hepatic elimination and hence bumetanide does not accumulate. Elimination of torasemide is also independent of its renal excretion. Thus in renal failure, torasemide is the only loop diuretic in which the plasma concentration is strictly dose dependent. Loop diuretics follow a number of different metabolic pathways, but this may not be clinically relevant.

Diuretics↗
PubMed1994

Do different dialysis-membranes affect beta 2-microglobulin kinetics during chronic hemodialysis?

Hemodialysis is not an absolute prerequisite for the formation of beta 2-microglobulin amyloidosis, but it enhances the progression of this complication related to long-standing renal failure. Thus the clearance and turnover of beta 2-microglobulin seems to play a major role in this disease. In a prospective multicenter study the beta 2-microglobulin clearance was studied in 87 patients starting hemodialysis. Serum samples were taken prior to and after the first dialysis session and also before and after dialysis at 4, 6, 12, 16, 26 and 52 weeks. Patients were either treated by cuprophane or a polyacrylonitril membrane. At the start, the mean serum beta 2-microglobulin level was about 18 mg/L in patients treated with a cuprophane membrane, but the levels increased after hemodialysis and reached a plateau, which was always higher than in those treated with polyacrylonitril, which cleared beta 2-microglobulin from the serum. However, after 12 months the difference was no longer significant. Thus beta 2-microglobulin excretion during dialysis differs between the two membranes, but seems to lose its significance for the beta 2-microglobulin serum level in chronic hemodialysis treatment.

Acrylic Resins↗
PubMed1994

[Therapy of primary chronic glomerulonephritis].

Primary chronic glomerulonephritis may emerge clinically as acute nephritis, the nephrotic syndrome as well as asymptomatic hematuria and proteinuria. Therapeutic consequences still depend on the morphological diagnosis. In cases of minor proteinuria [< 3,5 g/24 h] immunosuppressive therapy is not superior to symptomatic therapy. In patients with nephrotic syndrome immunosuppressive therapy depends on the morphological diagnosis. Glucocorticoids are the therapy of choice in minimal changes glomerulopathy and should be tried in focal segmental sclerosing glomerulonephritis. Steroids may be tried in pure mesangial as well as in IgA and IgM nephropathy. Especially Ponticelli claims significant therapeutic success in patients with membranous glomerulonephritis treated with Prednisolone and Chlorambucil. Failures and relapses may be treated with Cyclophosphamide, Chlorambucil or Cyclosporin A. Anticoagulants may be advantageous in the therapy of membranoproliferative glomerulonephritis.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

Acute and chronic effects on cholesterol biosynthesis of LDL-apheresis with or without concomitant HMG-CoA reductase inhibitor therapy.

To determine the acute and long-term effects of low density lipoprotein (LDL) reduction on cholesterol biosynthesis, we studied changes in the cholesterol precursors mevalonic acid (MVA) and lathosterol in patients with heterozygous familial hypercholesterolemia undergoing LDL-apheresis. Long-term LDL-apheresis in eight patients resulted in slight but insignificant increases in plasma MVA levels and lathosterol/cholesterol (L/C) ratios over 18 months. In short-term studies, six patients not on drugs and six patients treated with lovastatin or pravastatin had blood taken immediately before and after LDL-apheresis, and afterwards on days 1, 2, 3, 5, and 7. Plasma L/C ratios and MVA concentration did not change significantly on the first day after LDL-apheresis in those not on statin therapy (1.11 +/- 0.08 vs. 1.40 +/- 0.18, and 9.2 +/- 1.3 vs. 9.1 +/- 0.6 ng/ml, respectively) but increased in the statin-treated group (from 0.78 +/- 0.09 to 1.55 +/- 0.21, P = 0.003 and from 5.0 +/- 0.7 to 11.0 +/- 1.6 ng/ml, P = 0.008, respectively). There was no clear correlation between the changes in either of these precursors and the extent of reduction of total cholesterol by LDL-apheresis, but there was a strong inverse correlation with the post-apheresis LDL-cholesterol level (r = -0.77, P = 0.002 for L/C ratio; r = -0.75, P = 0.003 for MVA). Post-apheresis changes in L/C ratio and MVA were mutually correlated (r = 0.68. P = 0.01). We conclude that LDL-apheresis stimulates cholesterol biosynthesis transiently despite concomitant therapy with an HMG-CoA reductase inhibitor, the degree of stimulation being inversely related to the level to which the LDL-cholesterol was reduced.

Adult↗
PubMed1994

[Acute noninflammatory renal failure. New pathogenetic aspects in light of findings obtained in autopsy and biopsy of kidneys].

Thorough studies of kidney specimens obtained at autopsy or by renal biopsy revealed, that in noninflammatory acute renal failure oliguria/anuria is caused by increased activation o the renal renin-angiotensin system and increased generation of adenosine. At the polyuric phase moderately increased adenosine in kidney tissue seems to be the main factor responsible for decreased glomerular filtration.

Acute Kidney Injury↗
PubMed1993

Posttransplant renal artery stenosis--outpatient intraarterial DSA versus color aided duplex Doppler sonography.

A prospective trial was conducted to assess the accuracy of color aided duplex Doppler (CADD) sonography to rule out transplant renal artery stenosis (TRAS) and to determine feasibility and safety of intraarterial digital subtraction angiography (DSA) in hypertensive renal allograft recipients on an outpatient basis. All patients were hypertensive (n = 18, mean age: 42 +/- 11 years) and underwent CADD and an i.a. DSA with 4F catheters. There was a 4 hour rest post DSA. Duplex Doppler measurements of maximum velocity were obtained. Absolute values of > or = 100 cm/s were considered indicative to suspect TRAS. DSA revealed severe TRAS in 4 patients (22%). The stenoses were located near the iliorenal anastomosis (n = 2) and at the bifurcation of the renal artery (n = 2). Duplex Doppler classified twelve (67%) renal artery pedicles normal (maximum velocity: 79 +/- 23 cm/s). TRAS was suspected in 6 patients with a maximum velocity of 159 +/- 48 cm/s (P < 0.01). False positive CADD diagnoses were due to tortuous graft vessels and a postbiopsy arteriovenous fistula. Sensitivity of CADD was 100%, specificity 86%. There were no DSA related complications. No impairment of graft function occurred. CADD allows renal angiography to be reserved to clarify an inconclusive ultrasound study and for definite diagnosis of angiomorphology and lesion classification. Intraarterial DSA of renal grafts in outpatients may be performed without an increased risk of procedure-related complications.

Adult↗
PubMed1993

Different effects of two methods of low-density lipoprotein apheresis on the coagulation and fibrinolytic systems.

OBJECTIVE: Immunoadsorption (IMA) and dextran sulfate adsorption (DSA) are two methods for selective extracorporeal elimination of low-density lipoproteins which are known as LDL apheresis. Their influence on haemostasis until now is widely unknown. DESIGN: The effects of both LDL apheresis procedures on the coagulation and fibrinolytic systems were compared amongst five patients treated with IMA and four patients who received a DSA therapy. SUBJECTS: All patients with severe heterozygous familial hypercholesterolaemia were participants in a long-term LDL apheresis programme with treatments every 1-2 weeks. INTERVENTION: Combined anticoagulation with heparin and citrate in IMA, and also heparin exclusively in DSA were used for the extracorporeal circulation. MEASURES: Blood samples were taken immediately before and after a single LDL apheresis and five times during the weekly interval until the next therapy. RESULTS: DSA had a significantly greater effect on standard clotting tests than IMA at the end of plasma therapy despite identical dosages of heparin. DSA caused a considerable reduction of the coagulation factors V, VIII:C, vWF:Ag, XI, XII, and prekallikrein by 48-99% at the end of apheresis treatment whereas only factor VIII:C showed a marked decrease of 72% after IMA. All abnormalities of the global coagulation tests and of most clotting factors were restored 1 day after treatment in both procedures followed by a moderate rebound phenomenon of single coagulation factors during the next few days in IMA-treated patients. CONCLUSION: DSA exerts a more profound effect on the coagulation system than IMA by a substantial co-elimination of various clotting factors in addition to the desired removal of atherogenic lipoproteins.

Adsorption↗
PubMed1993

Microalbuminuria in essential hypertension. Reduction by different antihypertensive drugs.

The effects of four different antihypertensive drugs (the Ca(2+)-channel blocker felodipine, the beta-blocker metoprolol, the angiotensin converting enzyme inhibitor ramipril, and the alpha-blocking agent doxazosin) on microalbuminuria and renal hemodynamics were evaluated in a double-blind, crossover study in 17 patients (10 women, seven men, aged 39 +/- 14 years) with mild-to-moderate essential arterial hypertension and microalbuminuria. Patients were studied after a 2-week placebo phase preceded by 2 weeks off all medication and after 12 weeks of treatment with each drug. Between each drug treatment, there was another 14-day placebo washout period. At the end of the study, we performed two additional 2-week placebo periods. After each placebo and treatment period, we measured albumin excretion during a 3-day collecting period. Renal hemodynamics were assessed by clearance techniques (inulin and p-aminohippurate clearance) at the end of the first and last placebo periods and after each treatment period. All drugs reduced mean arterial pressure and microalbuminuria to a similar and statistically significant (p < 0.05) extent (mean arterial pressure: placebo phase, 116 +/- 5 mm Hg; felodipine, 101 +/- 4 mm Hg; metoprolol, 101 +/- 5 mm Hg; ramipril, 101 +/- 4 mm Hg; doxazosin, 102 +/- 5 mm Hg; urinary albumin excretion: placebo phase, 46 +/- 50 mg/day; felodipine, 18 +/- 23 mg/day; metoprolol, 14 +/- 12 mg/day; ramipril, 16 +/- 16 mg/day; doxazosin, 14 +/- 14 mg/day). Mean arterial pressure levels and urinary albumin excretion returned to baseline after the last placebo period (110 +/- 6 mm Hg and 40 +/- 46 mg/day, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Modification of renal hemodynamics and proteinuria in patients with arterial hypertension and kidney diseases].

A considerable number of hormones control renal perfusion to preserve glomerular filtration. We used the "captopril test" to characterize patients with renal-vascular hypertension. This study revealed a group of patients which reacted to 25 mg of captopril with a significant increase of plasma renin activity, but angiography excluded a renal artery stenosis. These patients had significantly more hypertensive organ damage than a control-group, including a significant microalbuminuria. Consequently, we infused a subpressure dose of angiotensin II to investigate its impact on albuminuria in these patients. Although angiotensin II induced hyperfiltration, microalbuminuria was not increased. Because this finding could have therapeutic relevance, we investigated the significance of different antihypertensive drugs (beta-blocker, alpha-blocker, Calcium antagonists, ACE-inhibitor) on microalbuminuria in patients with arterial hypertension. Renal hemodynamics were influenced as expected, but blood-pressure and microalbuminuria were reduced to the same extent by all antihypertensives. In contrast to these results, we could demonstrate significantly different influences of a beta-blocker and an ACE-inhibitor on proteinuria in patients with primary glomerulonephritis. These results suggest different effects of antihypertensive drugs on renal protein excretion depending on the actual disease.

Adrenergic beta-Antagonists↗
PubMed1992

[Proteinuria and atherogenic risk].

The relationship between blood-lipid levels and severity of proteinuria was examined retrospectively in 30 patients (12 males, 18 females; mean age 39 [18-58] years). All patients had histologically confirmed glomerulonephritis (minimal change: n = 7, perimembranous: n = 8, focal sclerosing: n = 6, rapid progressive: n = 3, mesangio-proliferative: n = 4, membrano-proliferative: n = 1, diabetic glomerulosclerosis: n = 1). None was taking lipid-lowering drugs. Patients were classified according to the degree of proteinuria. In group 1 (proteinuria less than 5 g/d, n = 13) the LDL-HDL ratio averaged 4.4; in group 2 (proteinuria 5.0-10.0 g/d, n = 10) the average ratio was 8.8, and in group 3 (proteinuria greater than 10.0 g/d, n = 7) 13.3. Total cholesterol concentration also rose with increasing proteinuria (to 300 +/- 87 mg/dl, 375 +/- 168 mg/dl and 464 +/- 143 mg/d, respectively). The size of the LDL-HDL ratio and the level of total cholesterol did not correlate with the degree of excretory renal failure. These results point to an impressive correlation between the degree of proteinuria and the level of LDL-HDL ratio as a measure of atherogenic risk for a given patient.

Adult↗
PubMed1992

Pharmacokinetic and blood pressure effects of carvedilol in patients with chronic renal failure.

The pharmacokinetic and acute systemic haemodynamic effects of a single oral dose of 50 mg carvedilol has been studied in 24 hypertensive patients with chronic renal failure. The patients were stratified into 3 groups according to the creatinine clearance: I 51-90 ml.min-1; II 26-50 ml.min-1; III 4-25 ml.min-1. The area under plasma level time curve AUC, the elimination half-life t1/2, the maximum plasma concentration Cmax, the time to peak concentration tmax were not significantly different between groups, whereas the amount of unchanged drug or metabolite excreted in urine Ae and the renal clearance CLR of carvedilol and its metabolites M2, M4, M5 were significantly decreased in Group III. Blood pressure and heart rate decreased in all 3 groups of patients after acute administration of 50 mg carvedilol. Mild adverse effects were reported in 6 patients. Despite a decrease in the renal clearance of carvedilol and of its metabolites with decreasing kidney function, its main pharmacokinetic parameters remained unchanged. The present results suggest that the dose of carvedilol need not be reduced in hypertensive patients with chronic renal failure.

Administration, Oral↗
PubMed1992

Renal hemodynamics and reduction of proteinuria by a vasodilating beta blocker versus an ACE inhibitor.

The effects of a nonselective beta-adrenergic blocking drug with beta-2 agonist activity (dilevalol 200 mg) on proteinuria and renal hemodynamics were evaluated in a double-blind crossover study versus an ACE inhibitor (enalapril 5 mg) in eight patients with glomerulonephritis, moderate renal function impairment and proteinuria greater than 1 g/24 hr. Patients were studied after a one week placebo phase while off all other medications, except steroids in a few cases, and after three weeks of treatment. A 10-day placebo washout perod was included between the various drug treatments. During each period renal hemodynamics were measured by clearance techniques, and urinary protein excretion as well as fractional clearance of albumin and IgG were determined. Both drugs reduced mean arterial pressure and proteinuria to a similar extent [mean arterial pressure: placebo 108 +/- 13 mm Hg; dilevalol 103 +/- 11 mm Hg (P less than 0.05); enalapril 103 +/- 12 mm Hg (P less than 0.05); protein excretion: placebo 5.1 +/- 4.2 g/day; dilevalol 3.3 +/- 3.0 g/day (P less than 0.05); enalapril 2.8 +/- 2.8 g/day (P less than 0.05)]. The antiproteinuric effect was greater with enalapril than dilevalol. Dilevalol reduced GFR [baseline inulin clearance: 73.3 +/- 38 ml/min/1.73 m2; after dilevalol: 63.3 +/- 28 ml/min/1.73 m2 (P less than 0.05)] and the decrease of proteinuria correlated positively with the reduction of GFR. Enalapril did not significantly lower the GFR (inulin clearance during enalapril 66.8 +/- 23 ml/min/1.73 m2) and the reduction of proteinuria did not correlate with the lowering of the GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Renal haemodynamics and organ damage in young hypertensive patients with different plasma renin activities after ACE inhibition.

We describe our observations concerning differences in two groups of young hypertensive patients according to their renin activities after ACE inhibition. Seventeen of these patients (age 26 +/- 7 years), so far untreated, were investigated prospectively for hormone levels (renin, aldosterone, vasopressin), microalbuminuria, renal haemodynamics (inulin and PAH clearance) and signs of organ damage (echocardiography, fundoscopy). Secondary forms of hypertension were excluded by routine methods, including angiography. We differentiated two groups of young hypertensive patients. Group 1 (n = 9) had a false positive captopril test with elevated renin activities after ACE inhibition with captopril (8.4 +/- 5 ng/ml per hour) compared to group 2 (renin activity: 2.2 +/- 1.3 ng/ml per hour) or an increase of greater than 400% of renin activity after ACE inhibition. Baseline renin activities and sodium excretion did not differ between the groups. Group 1 also showed significantly greater GFR, FF, and microalbuminuria, as well as signs of organ damage, with left ventricular hypertrophy and hypertensive changes in fundoscopy. There were no differences between the groups concerning mean arterial blood pressure and duration of hypertension. In conclusion, we were able to demonstrate that patients with highly stimulated renin activities showed signs of visceral organ damage and renal hyperfiltration compared to the normal renin activity group after ACE inhibition. Investigations of the renin-angiotensin-aldosterone system with ACE inhibitors might constitute a helpful indicator of renal changes and organ damages in young hypertensive patients.

Adult↗