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Biomedical subjects

C Wanner

Publications and source records attributed to C Wanner.

At least 127 records · Page 7Linked to original sources
PubMed1991

Hyperlipoproteinemia in chronic renal failure: pathophysiological and therapeutic aspects.

Dyslipidemia of chronic renal failure is of multifactorial origin. Decreased activity of lipoprotein lipase and hepatic triglyceride lipase, peripheral insulin resistance, hyperparathyroidism and L-carnitine deficiency are the contributing factors. This results in a disturbed catabolism of chylomicron, accumulation of very-low-density (VLDL) and intermediate-density (IDL) lipoproteins as well as incompletely cleared remnant particles, whereas low-density lipoprotein (LDL) levels are diminished. There is current debate as to whether cardiovascular disease is accelerated and whether hyperlipidemia should specifically be treated. In addition, there have been few means of influencing these metabolic alterations. Drug incompatibility and consequently side effects render treatment difficult. The drugs that have been most tested for lipid lowering in chronic renal failure are the fibric acids. By their mode of action, they are the logical choice. Dose reduction overcomes major side effects such as myopathy and rhabdomyolysis. The second generation of fibric acid derivatives (gemfibrozil and beclobrate) show several advantages over formerly used derivatives. Treatment with lovastatin and simvastatin appears to be safe and is recommended in a minority of patients with predominantly elevations of LDL. HMG-CoA reductase inhibitors also lower remnant particles effectively in hemodialysis (HD) patients. L-Carnitine and low-molecular-weight heparin have been shown to influence VLDL rich in triglycerides in a subset of patients on HD. In posttransplant hyperlipidemia, diet remains the first course of action in all patients. When this approach fails, the new lipid-lowering agents, especially fibric acids, appear to be safe in short-term studies in azathioprine- and ciclosporin-treated patients. Lovastatin has been shown to be safe in stable renal transplant patients. Its toxicity seems to depend mainly on high ciclosporin whole blood through or plasma levels.

Humans↗
PubMed1991

Crescentic glomerulonephritis in Wegener's granulomatosis: morphology, therapy, outcome.

Fourteen patients with Wegener's granulomatosis (WG) and severe renal and extrarenal involvement were studied (serum creatinine on admission 5.8 +/- 3.4 mg/dl). Renal histology showed a necrotizing, crescentic glomerulonephritis in all patients. Despite advanced renal disease on admission cyclophosphamide, steroids (in 13 patients) and plasma exchange (in 9 patients) caused a rapid and sustained improvement of renal function. Four patients required intermittent hemodialysis over a period of one week. After 2 weeks of treatment serum creatinine values below 2 mg/dl (n = 4) indicated a nearly complete recovery of renal function in the long-term follow up (mean serum creatinine achieved after 12 months therapy: 1.1 +/- 0.1 mg/dl (n = 4). Therefore serum creatinine values observed after 2 weeks of therapy, appear to be of prognostic value with regard to renal outcome. No relapse of active WG or progressive renal deterioration was observed during follow-up (22 +/- 13 months) except in one patient with persisting renal impairment. Three patients died (staphylococcus sepsis, intracerebral hemorrhage during hypertensive crisis, pulmonary embolism) during the first two months of therapy. The decline of serum creatinine seemed to be a better indicator of successful therapy than the decrease of anticytoplasmatic antibody (ANCA), erythrocyte sedimentation rate (ESR) and hematuria. On admission ANCA titer neither correlated with serum creatinine, the degree of renal involvement, nor was it of prognostic value. ANCA, serum creatinine and hematuria normalized within 2 to 8 months, whereas ESR and proteinuria remained elevated. Our data indicate a good prognosis of WG even with advanced renal involvement and generalized vasculitis provided aggressive treatment is performed early.

Acute Disease↗
PubMed1991

Beclobrate:pharmacodynamic properties and therapeutic use in hyperlipidemia.

Beclobrat is a new fibric acid derivative with potent cholesterol- and triglyceride-lowering effects. Pharmacodynamic and pharmacokinetic investigations suggest that once-daily administration in a dosage of 100 mg is admissible. In comparison with other lipid-lowering drugs such as dose, even when calculated on a molar basis, is as effective as 300 mg fenofibrate, 600 mg bezafibrate or 900 mg gemfibrozil. The effectiveness of the drug has been investigated in a variety of studies including patients with hyperlipidemia types IIa, IIb and IV and patients suffering from secondary hyperlipidemia attributable to diabetes mellitus, liver disease, end-stage renal failure requiring hemodialysis, and kidney transplantation. According to the type of hyperlipidemia studied, the mean reduction of LDL-cholesterol ranges from -10% to -28% and that of triglycerides from -20% to -58%. Mean serum HDL-cholesterol increase has been reported to be 8.5-23.9%. In general, side-effects of beclobrate therapy are comparable with those of other fibric acid derivatives, but have to be investigated carefully in a greater number of patients. Advantages in clinical use are administration of a small capsule in a single daily dose. This has been shown to increase patient compliance and is especially useful for treatment of hyperlipidemia in those patients requiring antihyperlipidemic combination therapy or additional medication for further diseases.

Benzhydryl Compounds↗
PubMed1990

Plasma and red blood cell carnitine and carnitine esters during L-carnitine therapy in hemodialysis patients.

Plasma and red blood cell (RBC) carnitine and acylcarnitines were determined in 20 hemodialysis (HD) patients during three different L-carnitine dosages (1, 5, and 15 mg/kg body wt), each for 3 mo. Before L-carnitine treatment, free carnitine was significantly lowered in plasma but elevated in RBCs compared with healthy subjects. Short-chain acylcarnitines were elevated in plasma and normal in RBCs. HD therapy decreased plasma free and acylcarnitines markedly but did not influence RBC values. Low-dose L-carnitine treatment normalized both plasma- and RBC-free carnitine. Dosages of 5 and 15 mg/kg body wt increased plasma and intracellular carnitine and carnitine esters impressively. Plasma and RBC carnitine fractions remained elevated even after a 6-wk washout period. Low-dose L-carnitine treatment is sufficient to correct disturbed plasma and RBC carnitine and carnitine esters of HD patients. Elevated RBC carnitine esters decreased very slowly, suggesting low RBC carnitine turnover. Carnitine overdosage should be prevented in those patients who benefit from carnitine therapy.

Adult↗
PubMed1990

Plasma levels of main granulocyte components during hemodialysis. Comparison of new and reused dialyzers.

Complement activation occurs during hemodialysis, and its intensity depends on the type of dialyzer and whether it is new or reused. Neutrophil degranulation also occurs during hemodialysis with release of lactoferrin, myeloperoxidase and elastase. However, it is unclear whether this event is induced by complement activation and whether it is attenuated by reuse. We examined complement activation and neutrophil degranulation during 10 consecutive hemodialyses using the same cuprophane dialyzer. Also the effect of rinsing the latter with 25% human albumin was studied. The rise in plasma C3a and C5a was markedly higher (p less than 0.01) during the first than the second use. Plasma levels of lactoferrin and myeloperoxidase increased significantly (p less than 0.01) during the first use, and levels were not affected by reuse. In contrast, plasma elastase increased with the first use and decreased with each subsequent use. Treatment of the dialyzer with albumin did not affect the magnitude of rise in plasma levels of C3a or lactoferrin but was associated with a significant reduction in plasma elastase. The data show that neutrophil degranulation is not dependent on complement activation and that the two processes could be dissociated.

Adult↗
PubMed1990

Control of hyperkalemia with fludrocortisone in a patient with systemic lupus erythematosus.

We describe the use of fludrocortisone in a patient with systemic lupus erythematosus, who initially presented with moderate renal insufficiency, high serum potassium, metabolic acidosis, low urine pH, and a high urinary anion gap indicating tubular dysfunction. Renal histology revealed membranous glomerulonephritis and interstitial inflammation. During the course of the disease the patient developed persistent severe hyperkalemia. Dietary potassium restriction and therapy with diuretics combined with cation exchange resins failed to decrease potassium levels sufficiently. Drug therapy including cyclosporin A, enalapril, atenolol, phenytoin, necessary to control active disease and severe hypertension contributed to elevated potassium levels. Effective correction of hyperkalemia was achieved by fludrocortisone treatment. We conclude that fludrocortisone is a potent therapeutic approach for selected patients suffering from life threatening hyperkalemia, in whom potassium elevating drugs cannot be withdrawn.

Adolescent↗
PubMed1989

Endocrine and metabolic abnormalities following kidney transplantation.

Various endocrine and metabolic disturbances associated with long standing uremia persist after kidney transplantation or arise from the use of immunosuppressive drugs. Hyperlipidemia for long time being implicated as the cause of corticosteroids is also observed in renal transplant recipients treated with cyclosporin A monotherapy. After conversion from cyclosporin to azathioprine serum cholesterol and triglyceride concentration fall, and elevation of LDL-cholesterol may also be reversed. There is a tendency for higher HDL-cholesterol in azathioprine and prednisolone treated transplant patients. Those patients who are at risk for clinically significant cholesterol elevations can be predicted by their pretransplant lipid levels, specifically the LDL-fraction. Risk-benefit ratio of conversion and of treatment with lipid-lowering drugs, especially with lovastatin, should be carefully examined, also in view of glucose intolerance. Higher incidence of diabetes mellitus requiring insulin therapy in cyclosporin treated transplant recipients has been reported. Cyclosporin may cause toxic effects on pancreatic beta-cells resulting in inhibition of insulin secretion. High doses of cyclosporin induce inhibition of glycogen synthesis in rat liver. Glucose intolerance is reversible after reduction of cyclosporin dose or conversion to azathioprine. Therefore glucose metabolism in kidney transplant recipients treated with cyclosporin should be carefully followed. Immunosuppressive therapy may affect reproductive function, arachidonate metabolism and renin-angiotensin-aldosterone system as well as posttransplant calcium and phosphate metabolism. Endocrine and metabolic abnormalities are associated with long standing uremia. After successful kidney transplantation several observations are normalized but further complications arise from the use of immunosuppressive drugs. The present paper reviews various endocrine and metabolic disturbances described following renal transplantation.

Animals↗
PubMed1989

[Hypophosphatemic osteomalacia in adults].

Hypophosphataemic osteomalacia occurred in a 38-year-old woman. The leading clinical symptom was severe bone pain. X-ray studies demonstrated fractures of the iliac crest and pubic and ischiadic bone, as well as Looser's zones and demineralization of the skeleton. Computerized densitometry of the bone revealed a 31% reduction of hydroxyapatite. Histological evaluation showed nearly absence of osteoclasts and extensive demineralisation of the bone. Hypophosphataemia (0.48 mmol/l), increased urinary phosphate clearance (36 ml/min), reduced renal-tubular reabsorption for phosphate (73%) and increased alkaline phosphatase (355 U/l) were present. Parathyroid hormone and 1,25-dihydroxyvitamin D were normal. No inborn errors, disturbances of the calcium metabolism or paraneoplastic signs could be detected. Defective renal tubular reabsorption of phosphate is likely to be the underlying cause of the disease. Phosphate supplementation and intermittent vitamin D administration remains the therapy of choice.

Adult↗
PubMed1989

Carnitine and carnitine esters in acute renal failure.

Plasma concentrations of carnitine and carnitine esters were determined in patients with multiple forms of acute renal failure with and without sepsis, and also before and after haemodialysis therapy. Total carnitine, free carnitine, short-chain and long-chain acylcarnitine values of both groups of acute renal failure patients were markedly elevated compared with healthy subjects and chronically uraemic patients undergoing regular haemodialysis treatment. Carnitine and carnitine esters did not differ between septic and non-septic patients before and after haemodialysis with dialysers made of cuprophane or polysulphone. Animal experiments with acutely uraemic rats were performed in order to determine whether the liver or the kidney may be responsible for elevated carnitine and carnitine esters in acute renal failure. Plasma and liver total carnitine, free carnitine, short-chain acylcarnitine and long-chain acylcarnitine were significantly elevated in sham-operated animals, and further in ureter ligated and bilateral nephrectomised rats. Skeletal muscle and heart muscle carnitine and carnitine esters remained the same as in sham-operated controls. Our data demonstrate markedly increased liver carnitine synthesis and carnitine acylation in an acute uraemic rat model even after binephrectomy and 48-h food depletion and in the presence of elevated serum carnitine concentrations. Furthermore, from our clinical study we conclude that there is no need for carnitine supplementation in patients who developed acute renal failure in the postoperative and post-traumatic state under adequate nutrition even when requiring daily haemodialysis.

Acute Kidney Injury↗
PubMed1989

Reduction of degranulation of polymorphonuclear leukocytes by immunosuppression in patients following cadaveric renal transplantation.

Plasma levels of main granulocyte components of patients after cadaveric renal transplantation were compared 9 days postoperative with the plasma levels of patients undergoing aortofemoral and iliacofemoral bypass operation or abdominal surgery. Lactoferrin values were significantly lower in patients under immunosuppression with cyclosporine and prednisolone, whereas plasma levels of myeloperoxidase were comparable in all 3 groups of patients. Plasma E-alpha 1 PI values were significantly lower in patients undergoing bypass operation compared to abdominal surgery but did not differ from patients undergoing cadaveric kidney transplantation. Within 22 days postoperatively, there was no difference in the plasma levels of main granulocyte components in patients after kidney transplantation with and without postoperative complications. In vitro incubation of heparinized whole blood and isolated granulocytes obtained from healthy subjects in the presence of CsA, azathioprine, or prednisolone were performed. Only CsA caused inhibition of spontaneous degranulation of polymorphonuclear neutrophils showing significant lower elastase and lactoferrin release. However, in vivo administration of CsA and prednisolone in transplant patients displayed no effect on in vitro degranulation of both whole blood samples and isolated granulocytes. Our data demonstrate that CsA after in vitro incubation inhibits spontaneous granulocyte degranulation but not after in vivo administration. However, in vivo administration of CsA and prednisolone reduces lactoferrin release under certain conditions, e.g., postoperative stress or during hemodialysis therapy.

Abdomen↗
PubMed1989

Enhanced plasma and intracellular levels of main granulocyte components in diabetics on dialysis.

Intracellular and plasma levels of main granulocyte components (elastase, lactoferrin) were investigated in 25 diabetic and 27 nondiabetic patients undergoing regular hemodialysis treatment (RDT) as well as in 14 diabetic and 11 nondiabetic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Diabetic patients on dialysis released more intragranular enzymes from neutrophils than their nondiabetic counterparts. Intracellular concentrations of granulocyte elastase and lactoferrin were only slightly higher in uremic diabetics than in uremic nondiabetics. However, both diabetic and nondiabetic hemodialysis patients displayed significantly lower cellular elastase and lactoferrin levels than healthy subjects. In addition, the diabetic dialysis patients had more protein catabolic fragments in the plasma as determined by trichloroacetic acid solubility. These observations were cited to support the hypothesis that not only is the hemodialysis procedure itself (with exposure to membranes) catabolic, but the diabetics are in double jeopardy. Thus, neutrophil abnormalities in diabetics on dialysis might affect the plasmatic proteinase inhibitor system and contribute to enhanced plasma protein degradation as well as to enhanced susceptibility to infections.

Adult↗
PubMed1989

Ketogenic and antiketogenic effects of L-carnitine in hemodialysis patients.

Eighteen hyperlipidemic hemodialysis patients were treated with 1, 5, and 15 mg L-carnitine/kg body weight (each dose was given for three months) given intravenously at the end of the dialysis therapy. Low dose L-carnitine treatment caused an increase in plasma total carnitine (TC), short chain acylcarnitine (SCC), and long chain acylcarnitine (LCC). An increase in plasma free carnitine (FC) occurred only in the 10 responders who showed a significant decrease in serum triglycerides. Serum VLDL triglycerides, VLDL cholesterol and VLDL phospholipids also decreased in the responders compared to nonresponders. There was no difference in HDL- and LDL-lipoproteins in both responders and nonresponders. L-carnitine in doses of 5 or 15 mg/kg body weight caused markedly elevated plasma levels of all carnitine fractions but no further lipid lowering effect. Moreover, enhanced serum triglycerides were observed in some hemodialysis patients. Thirteen out of 15 patients displayed an increase of HDL triglycerides and 5, an increase of VLDL triglycerides. Our data suggest that low doses of L-carnitine are effective in treating hypertriglyceridemia in selected patients. Low dose L-carnitine also avoids unphysiological high plasma levels of carnitine and carnitine esters and prevents antiketogenic effects in hemodialysis patients.

Acylation↗
PubMed1988

Serum carnitine levels and carnitine esters of patients after kidney transplantation: role of immunosuppression.

Serum levels of carnitine and carnitine esters were measured in different groups of patients after cadaveric renal transplantation and compared with those of healthy subjects as well as azotemic and uremic patients. In all groups of patients serum levels of total carnitine (TC), free carnitine (FC), short-chain acylcarnitine (SCC), and long-chain acylcarnitine (LCC) increased with reduction of kidney function. However, cyclosporin- and prednisone-treated transplant patients with impaired kidney function displayed significantly higher TC, FC, and SCC compared with transplant patients under immunosuppression with azathioprine and prednisone. This group of cyclosporin-treated patients showed also significantly elevated serum cholesterol suggesting that carnitine deficiency is not responsible for the observed abnormalities in lipid metabolism after renal transplantation. Urinary excretion of TC, FC, SCC, and LCC decreased with reduction of kidney function without differences between cyclosporin- and azathioprine-treated patients. Single dose L-carnitine administration (10 mg/kg body weight IV) resulted in significantly higher TC, FC, SCC, and LCC values of azotemic patients with and without immunosuppression than in healthy subjects. Acylation of the administered carnitine was comparable in healthy controls and azotemic patients. Increased values of short-chain and long-chain acylcarnitine, therefore, seem to depend on the excretion of the diseased kidney(s). Our data demonstrate abnormalities in carnitine metabolism in patients with impaired kidney function. These alterations are further influenced by immunosuppressive drugs.

Acylation↗
PubMed1988

Plasma levels of pancreatic secretory trypsin inhibitor in relation to amylase and lipase in patients with acute and chronic renal failure.

Plasma levels of pancreatic secretory trypsin inhibitor (PSTI), lipase and amylase were measured in patients with chronic renal failure (CRF), patients undergoing regular hemodialysis treatment (RDT) or continuous ambulatory peritoneal dialysis (CAPD), patients with acute renal failure (ARF) and patients following successful cadaveric kidney transplantation. Plasma PSTI values were 9.2 +/- 0.8 ng/ml in controls (CO), 156.9 +/- 16.2 ng/ml in CRF patients, 257.6 +/- 22.3 ng/ml in RDT patients, 376.8 +/- 57.5 ng/ml in CAPD patients and 2,300 +/- 276.9 ng/ml in patients with posttraumatic ARF. RDT patients with malignant diseases displayed significantly higher PSTI values (1,014 +/- 148.7 ng/ml; p less than 0.01) than RDT patients without malignancy. Transplant patients with normal kidney function (creatinine 1.25 +/- 0.1 mg/dl) showed significantly lower PSTI values (16.7 +/- 2.1 ng/ml) than transplant patients with impaired renal function (creatinine 4.7 +/- 0.5 mg/dl; PSTI 72.8 +/- 11.8 ng/ml; p less than 0.01). Daily urinary excretion of PSTI increased from 26.7 +/- 3.1 micrograms (CO) to 551.8 +/- 54.8 micrograms in CRF patients. In CAPD patients, daily peritoneal loss of PSTI was 164.3 +/- 58.4 micrograms. Plasma PSTI values increased during hemodialysis with dialyzers made of cuprophan (317.0 +/- 32.6 vs. 422.0 +/- 46.2 ng/ml; p less than 0.05) and decreased with polysulfone dialyzers (226.6 +/- 19.9 vs. 86.6 +/- 18.1 ng/ml). There was no correlation between PSTI and urea, creatinine, lipase or amylase in each tested group. Our results document markedly elevated plasma PSTI values in all forms of renal insufficiency, suggesting extrapancreatic PSTI production and/or reduced renal elimination.

Acute Kidney Injury↗