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Biomedical subjects

D Fliser

Publications and source records attributed to D Fliser.

At least 19 recordsLinked to original sources
PubMed2005

Biocompatibility parameters of different dialysis membranes assessed during systemic inflammation.

BACKGROUND: We explored whether biocompatible dialyzer membranes modulate the inflammatory response during blood contact in patients with systemic inflammation. METHODS: 15 patients with end-stage renal disease and systemic inflammation (mean serum C-reactive protein 86 +/- 4 mg/l) were randomly treated with Cuprophan (CU), polyamide (PA) and vitamin-E coated (VEC) membrane-based dialyzers. RESULTS: Changes in blood pressure, capillary blood oxygen saturation and differential blood counts during the hemodialysis session were not significantly different between the three dialyzers. Baseline blood levels of activated circulating complement (C3a) were more than 100 times above normal, and unlike expected they decreased during hemodialysis treatments (CU: from 7,389 +/- 783 to 5,423 +/- 761 ng/ml; PA: from 7,379 +/- 980 to 5,690 +/- 714 ng/ml; VEC: from 7.377 +/- 714 to 5,360 +/- 1,005 ng/ml; all n.s.). No significant differences between treatments were found with respect to changes in blood concentrations of TNF-alpha, interleukin-6 and interleukin-1 receptor antagonist as well as ICAM-1 (CU: from 451 +/- 41 to 477 +/- 41 ng/ml; PA: from 437 +/- 42 to 449 +/- 40 ng/ml; VEC: from 461 +/- 43 to 460 +/- 47 ng/ml). Furthermore, generation of reactive oxygen species by mononuclear blood cells was comparable during hemodialysis with the CU, PA and VEC dialyzer. CONCLUSION: The choice of dialyzer membrane material does not affect most aspects of biocompatibility when patients have significant systemic inflammation. This confounding variable should be taken into account in studies exploring the effects of biocompatible dialyzer membranes.

Female↗
PubMed2005

Asymmetric dimethylarginine (ADMA): the silent transition from an 'uraemic toxin' to a global cardiovascular risk molecule.

Endothelial dysfunction as a result of reduced bioavailability of nitric oxide (NO) plays a central role in the process of atherosclerotic vascular disease. In endothelial cells NO is synthesized from the amino acid l-arginine by the action of the NO synthase (NOS), which can be blocked by endogenous inhibitors such as asymmetric dimethylarginine (ADMA). Acute systemic administration of ADMA to healthy subjects significantly reduces NO generation, and causes an increase in systemic vascular resistance and blood pressure. Increased plasma ADMA levels as a result of reduced renal excretion have been associated with atherosclerotic complications in patients with terminal renal failure. However, a significant relationship between ADMA and traditional cardiovascular risk factors such as advanced age, high blood pressure and serum LDL-cholesterol, has been documented even in individuals without manifest renal dysfunction. As a consequence, the metabolism of ADMA by the enzyme dimethylarginine dimethylaminohydrolase (DDAH) has come into the focus of cardiovascular research. It has been proposed that dysregulation of DDAH with consecutive increase in plasma ADMA concentration and chronic NOS inhibition is a common pathophysiological pathway in numerous clinical conditions. Thus, ADMA has emerged as a potential mediator of atherosclerotic complications in patients with coronary heart disease, peripheral vascular disease, stroke, etc., being the culprit and not only an innocent biochemical marker of the atherosclerotic disease process.

Amidohydrolases↗
PubMed2004

One for all--a multi-use dialysis system for effective treatment of severe thallium intoxication.

Guided by the idea of providing a stable electrolyte composition of the dialysate, the late Bernd Tersteegen designed a machine ingeniously combining the advantages of a closed tank hemodialysis system with the efficacy and bacteriological safety of a single-pass system. Several thousand dialysis sessions have been performed with this system in the chronic hemodialysis population. Recently, highly efficient (i.e. high volume) dialysis systems have been successfully introduced for the treatment of critically ill patients in the intensive care unit as extended dialysis. Furthermore, they can also be a safer, more effective and less costly alternative to traditional extracorporeal techniques in the treatment of severe intoxication. In a case-based approach, we review the increasing use of such a system.

Critical Care↗
PubMed2004

Subpressor dose asymmetric dimethylarginine modulates renal function in humans through nitric oxide synthase inhibition.

Increased blood concentrations of the endogenous nitric oxide (NO) synthase inhibitor asymmetric dimethylarginine (ADMA) have been linked to high blood pressure and to cardiovascular mortality. We evaluated the effects of a subpressor ADMA dose on NO production, renal hemodynamics, sodium handling and active renin and noradrenalin plasma concentrations in 12 healthy subjects (age 26 +/- 1 year) using a double-blind placebo-controlled study design. Infusion of ADMA caused a significant decrease in plasma cyclic guanosine monophosphate (cGMP) levels, i.e. the second messenger of NO (from 6.1 +/- 0.4 to 4.3 +/- 0.3 pmol/l; p < 0.05). In parallel, effective renal plasma flow (ERPF) decreased while renovascular resistance (RVR) increased significantly (ERPF from 667 +/- 9 to 603 +/- 10 ml/min/1.73 m2; RVR from 79 +/- 2 to 91 +/- 2 ml/min/mm Hg; both p < 0.05 vs. baseline). Infusion of placebo did not cause significant changes in plasma cGMP levels, ERPF and RVR (cGMP from 5.7 +/- 0.5 to 5.9 +/- 0.6 pmol/l; ERPF from 665 +/- 12 to 662 +/- 11 ml/min/1.73 m2; RVR from 79 +/- 2 to 78 +/- 2 ml/min/mm Hg; all non-significant). Moreover, urinary sodium excretion was significantly lower with infusion of ADMA as compared with placebo infusion (128 +/- 8 vs. 152 +/- 7 micromol/min; p < 0.05). In contrast, blood pressure, active renin and noradrenalin plasma concentrations did not change significantly with either infusion protocol. Acute infusion of a subpressor ADMA dose modulates several aspects of renal function in humans without affecting the activity of the renin-angiotensin and sympathetic system. Whether chronic (intrarenal) NO synthase inhibition in individuals with increased ADMA blood levels may cause persistent renal vasoconstriction and sodium retention must be evaluated.

Adult↗
PubMed2004

[Modern differential therapy with diuretics].

Diuretics block different electrolyte transporters in renal tubular cells. Their predominant action is inhibition of renal sodium chloride reabsorption, however, and achievement of a negative body sodium balance is the principal goal of diuretic therapy in patients with hypertension and edema. Several classes of diuretics can be distinguished with respect to the sites of sodium reabsorption along the nephron, but loop diuretics and distal-tubular diuretics (incl. thiazides) are the most widely used. The latter have a less potent natriuretic effect than loop diuretics, but their long duration of action predispose them for treatment of patients with uncomplicated hypertension. In conditions of gross edema, e.g. heart and/or renal failure, distal-tubular diuretics lose their efficacy and must be replaced by or combined with loop diuretics ("sequential nephron blockade"). Aldosterone antagonists are unique among diuretics because they improve survival in patients with heart failure independently of their effect on sodium metabolism.

Benzothiadiazines↗
PubMed2004

Low dialysance of asymmetric dimethylarginine (ADMA)--in vivo and in vitro evidence of significant protein binding.

BACKGROUND: Increased blood levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) predict cardiovascular mortality in patients with end-stage renal disease. Despite its low molecular weight, available information on the impact of hemodialysis (HD) on ADMA plasma levels is controversial. METHODS: We assessed plasma concentrations, dialyzer clearance and total amount of ADMA removed in 30 patients with end-stage renal disease during regular HD. In addition, plasma ADMA levels were assessed in 10 patients with acute renal failure treated with extended HD. RESULTS: Regular HD decreased plasma creatinine (from 774 +/- 42 to 312 +/- 17 micromol/l) and urea (from 24.5 +/- 1.5 to 8.4 +/- 0.5 mmol/l) concentrations significantly (both p < 0.001), whereas plasma ADMA remained unchanged (4.35 +/- 0.19 vs. 4.76 +/- 0.24 micromol/l). ADMA clearance was 92 +/- 6 ml/min, and the total amount removed in the spent dialysate was 37 +/- 4 micromol. The clearances of creatinine (161 +/- 3 ml/min) and of urea (173 +/- 3 ml/min) were significantly higher. Furthermore, even during extended HD, plasma ADMA concentrations did not decrease significantly (1.73 +/- 0.22 vs. 1.63 +/- 0.18 micromol/l). CONCLUSION: In conclusion, dialysance of ADMA is markedly lower than expected from its molecular weight because of significant protein binding of the substance. Since markedly increased ADMA blood concentrations have been linked to cardiovascular complications due to atherosclerosis in patients with ESRD, new strategies should be evaluated to remove this putative uremic toxin.

Arginine↗
PubMed2003

Endogenous nitric oxide synthase inhibitors and renal perfusion in patients with heart failure.

BACKGROUND: Patients with heart failure are characterized by impaired nitric oxide-dependent endothelial vasodilation and, in addition, by reduced renal perfusion. DESIGN: We assessed blood concentrations of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) as well as renal haemodynamics to compare normotensive patients with mild heart failure (n = 12, seven males, 70 +/- 1 years, 72.0 +/- 2.7 kg, 92 +/- 2 mmHg, NYHA I/II) and healthy subjects matched with respect to gender, age and body weight (n = 12, seven males, 69 +/- 2 years, 72.7 +/- 2.5 kg, 88 +/- 2 mmHg). RESULTS: Plasma ADMA concentration and renovascular resistance (RVR) were significantly higher (P < 0.01) and effective renal plasma flow (ERPF) significantly lower (P < 0.01) in the patients with heart failure (ADMA 4.18 +/- 0.42 micro mol L-1, RVR 159 +/- 12 mmHg mL-1 min-1, ERPF 381 +/- 26 mL min-1 1.73 m-2) as compared with the healthy controls (ADMA 2.38 +/- 0.11 micro mol L-1, RVR 117 +/- 8 mmHg mL-1 min-1, ERPF 496 +/- 19 mL min-1 1.73 m-2). In contrast, plasma concentrations of l-arginine, homocysteine, symmetric dimethylarginine (i.e. the biologically inactive stereoisomer of ADMA) and plasma renin activity were not significantly different in both groups studied. In the multiple regression analysis, only plasma ADMA concentrations independently predicted reduced ERPF (r = -0.57; P < 0.003). CONCLUSIONS: In normotensive patients with heart failure plasma ADMA concentrations are markedly increased and related to reduced renal perfusion. Thus accumulation of this endogenous nitric oxide inhibitor may play a role in renal pathology in these patients.

Aged↗
PubMed2003

Efficiency of high-flux hemodialysis in the treatment of valproic acid intoxication.

Recently, highly efficient (i.e., high volume) dialysis systems have been successfully introduced for the treatment of critically ill patients in the intensive care unit. They also can be a safer, more effective, and less costly alternative to traditional extracorporal techniques in the treatment of severe intoxication. This holds true even if the substance to be eliminated is believed to be a poor candidate for dialysis treatment. We report a case of successful treatment of potentially life-threatening intoxication, with valproic acid (VPA) using a GENIUS batch dialysis system for combined standard and extended high-volume hemodialysis therapy. Concentration of VPA in the total collected dialysate were measured.

Adult↗
PubMed2002

High-flux hemodialysis--an effective alternative to hemoperfusion in the treatment of carbamazepine intoxication.

Carbamazepine intoxication is associated with seizures, coma, arrhythmias and death. In acute intoxication, charcoal hemoperfusion is employed for removal of the drug. This can be associated with thrombocytopenia, coagulopathy, hypothermia and hypocalcemia. Alternatively, we used high-efficiency hemodialysis with a batch dialysis system (Genius), lowering not only serum levels of carbamazepine but removing a considerable amount of the drug as measured in the dialysate. This treatment regimen was compared to treatment by hemoperfusion. A 3.5-hour high-flux hemodialysis was as effective as a 2-hour hemoperfusion. We conclude that high-efficiency hemodialysis is a safe and effective alternative for treating life-threatening carbamazepine intoxication.

Adult↗
PubMed2001

Serum cystatin C concentration as a marker of renal dysfunction in the elderly.

Serum cystatin C is a novel marker of renal function claimed to be superior to plasma creatinine. We assessed both parameters in young normotensive subjects (n = 12; 6 men; mean age, 25 +/- 2 years) and elderly normotensive and hypertensive subjects (n = 41; 19 men; mean age, 67 +/- 6 years). Glomerular filtration rate (GFR) was measured in all individuals using the inulin clearance (C(in)) technique. Compared with young subjects, mean GFR was modestly but significantly (P: < 0.001) less in elderly subjects (young, 119 +/- 11 mL/min/1.73 m(2) versus elderly, 104 +/- 12 mL/min/1.73 m(2)). Mean plasma creatinine concentration was identical in both groups (young, 0.93 +/- 0.11 mg/dL versus elderly, 0.93 +/- 0.10 mg/dL; P: < 0.90). Mean serum cystatin C concentration was significantly (P: < 0.001) greater in elderly subjects (0.84 +/- 0.10 mg/L) compared with young subjects (0.69 +/- 0.08 mg/L). In all but one elderly subject, plasma creatinine concentration was within the 95% confidence interval of plasma creatinine concentration in young subjects. Eleven of 41 elderly subjects (27%) had GFRs less than the lower 95% confidence interval, respectively, and 12 of 41 elderly subjects (29%) had a serum cystatin C concentration greater than the upper 95% confidence interval in young subjects. The correlation between serum cystatin C concentration and C(in) (r = -0.65; P: < 0.001) was considerably better than between plasma creatinine concentration and C(in) (r = -0.30; P: < 0.02). Serum cystatin C concentration is a better marker of renal dysfunction (ie, reduced GFR) than plasma creatinine concentration, at least in elderly subjects with plasma creatinine concentrations within the normal range.

Adult↗
PubMed2001

[Fulminant course of leptospirosis complicated by multiple organ failure].

We describe a case of a 39-year-old male, who initially presented with severe muscle pain, fever, shortness of breath and tachycardia. He was admitted to hospital with suspected myocarditis. The next days he developed a generalized icterus and acute renal failure. Suspecting leptospirosis an intravenous therapy with penicillin was started. Due to pulmonary and circulatory insufficiency intensive care was necessary. In course the patient developed all known manifestations of leptospirosis including, cardiac arrhythmia and asystolia due to AV-block III degrees, recurrent atelectases of the lungs, hyperbilirubinemia, thrombocytopenia, hepatitis, pancreatitis, very severe rhabdomyolysis and polyradiculitis with areflexia and tetraplegia. Additionally, the patient had a transient hyperthyreosis, which has not been described in the literature so far. After 33 days the patient left the intensive care unit and was discharged out of hospital a fortnight later. 4 weeks later he was able to return to work. The only residuum of this illness is a partial paresis of his right quadriceps muscle.

Acute Kidney Injury↗
PubMed2001

Angiotensin II subtype 1-receptor antagonists in the treatment of diabetic nephropathy.

Diabetic nephropathy has become the leading cause of terminal renal failure in all Western nations due to a steady increase of patients with the renal complication of type 2 (non-insulin-dependent) diabetes mellitus. A number of modifiable risk factors have been identified that predispose to and/or accelerate renal disease in patients with diabetes mellitus. Among these, the level of blood pressure, even in the range of normotension according to World Health Organization or Joint National Committee definition, is closely related to the rate of progression of diabetic nephropathy. This has been documented in patients with incipient (microalbuminuric) and in patients with manifest (proteinuric) diabetic renal disease. Consequently, the treatment of even normotensive diabetics has been recommended once microalbuminuria is present, and blood pressure values in the low normal range should be aimed for. The selection of antihypertensive agents is also important, however, since a 'renoprotective effect' has been documented for drugs that interfere with the renin-angiotensin-aldosterone system such as angiotensin converting enzyme inhibitors. Recently, a new class of drugs that selectively inhibits this system by specifically targeting the angiotensin II receptor has been developed. These angiotensin II subtype 1-receptor antagonists are efficacious antihypertensive agents with a side-effect profile similar to placebo. Evidence for a renoprotective effect in patients with diabetic nephropathy from a large controlled clinical trial is still awaited, but data generated in animal experiments and in smaller clinical trials are encouraging. Currently, these drugs are a valuable substitute for angiotensin converting enzyme inhibitors in patients who experience side effects such as intractable cough.

Angiotensin Receptor Antagonists↗