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Glomerular diseases are among the most common renal pathologies leading frequently to end-stage renal disease. Clinical disease can be divided into five different groups the features of which are determined by the underlying pathophysiology. One of these five clinical syndromes is the nephrotic syndrome, which is characterized by proteinuria > 3.5 g/day accompanied by hypalbuminemia, hyperlipoproteinemia and pronounced edema. The nephrotic syndrome may be the clinical manifestation of a row of underlying diseases. The pathophysiological basics had remained elusive for decades, yet recently significant progress which allows for establishing new therapeutic strategies has been made. A major breakthrough in understanding the function of the glomerular filter unit has been possible in the last years through both genetic and cell biological studies, which have revealed a crucial role for the visceral epithelial cells of the glomerulus - the podocytes. By now various factors have been found causing podocyte damage, such as toxines, immunological phenomena or systemic disease like diabetes mellitus., (© Georg Thieme Verlag KG Stuttgart · New York.)

No question, one of the leading causal factors for early atherosclerosis and coronary heart disease (CHD) is the abundance of LDL-cholesterol in the blood, exceeding limits of 100 mg/dl. Thus, recommendations for therapy focus on LDL-levels less than 100 mg/dl. With the introduction of the statins--a very potent family of lipid lowering agents--such target levels can be achieved in most of the patients, resulting in a drastic decrease of LDL, CHD incidences, as well as in a reduction of cardiac and total mortality. There is, however, a remaining small group of patients, who is more or less resistant to an adequate combination of dietary and drug therapy. For these patients, various techniques of apheresis are available for over 15 years. Some of them have been approved by the FDA in the US and comparable regulatory offices in Europe. The most extensive experimental and clinical experience was gathered with the H.E.L.P.-system of B. Braun Melsungen, which differs from other apheresis techniques by its efficiency to eliminate LDL, Lp(a), Fibrinogen and CRP simultaneously. The clinical results obtained up to day with the apheresis clearly demonstrate a significant reduction of risk factors and clinical events, as well as an excellent long-term tolerance.

In a prospective study, 20 patients (aged 48-67 years) with primary hyperlipoproteinaemia of phenotypes IIa, IIb, IV and with proven coronary sclerosis received four different doses of long-chain polyunsaturated omega-3 fatty acids. 0.18 to 1.1 g per day were administered in the form of fish oil capsules over four 2-week periods. The aim was to study the effect of different low dose supplementations of n-3 fatty acids on the plasmalipid- and lipoprotein composition and to determine a threshold of effectiveness. Significant reduction of the triglyceride level was registered in all subjects with the greatest decrease in those patients who presented with the highest base levels. The cholesterol and LDL-cholesterol values on average remained almost unchanged, apart from a significant increase of LDL-cholesterol in patients with type IV hyperlipoproteinaemia. The HDL-cholesterol fraction also showed a significant increase in type IIb patients which was related to alterations of the HDL-3 subfraction. The minimal effective dose of a daily administration of omega-3 fatty acids can be expected between 0.18 g and 0.35 g. The observed changes of plasmalipids and lipoproteins reflect the beneficial effect of long-chain polyunsaturated omega-3 fatty acids in respect to plasma-triglyceride reduction and HDL-cholesterol increase as seen in other studies, despite the use of supplementations far below 1 g per day.

Triglycerides and cholesteryl esters are non-polar molecules and, therefore, insoluble in aqueous fluids such as blood. Lipid transport in blood is only possible the formation of lipoproteins. This article proposes a concept for the treatment of hyperlipidemias that is based on lipoprotein pathology. The liver secretes the triglycerides and cholesteryl esters in the form of very-low-density lipoproteins (VLDL). Lipolysis hydrolyzes VLDL triglycerides, providing tissues with fatty acids. and gives rise to relatively cholesterol-enriched intermediate-density lipo- proteins (IDL) and low-density lipoproteins (LDL). IDL and LDL are removed from plasma by receptor-mediated cellular uptake. An increased plasma concentration of VLDL ensues in predominant hypertriglyceridemia (e.g. triglycerides 9 mmol/l, cholesterol 7 mmol/l). VLDL are not considered to be directly atherogenic, but increased levels of VLDL often occur together with an atherogenic decrease of high-density lipoproteins (HDL). Elevated VLDL levels respond well to dietary measures; fibric acid derivatives, nicotinic acid and omega-3-fatty acids also effectively lower VLDL. An increase in IDL leads to both hypertriglyceridemia (e.g. 3 mmol/l) and hypercholesterolemia (e.g. 7 mmol/l). IDL are considered directly atherogenic. Hyperlipidemias due to IDL respond to the same interventions as those due to VLDL. An increased blood level of LDL leads to hypercholesterolemia (e.g. 7 mmol/l) with normal triglyceride levels (e.g. 1 mmol/l); LDL are considered directly atherogenic. Dietary measures can reduce LDL levels by about 10%, but pharmacological treatment by inhibitors of cholesterol synthesis ('statins') and by ion exchange resins is much more effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyslipidemia is a common feature of renal failure. It is primarily caused by delayed catabolism of lipoprotein particles. This is due to decreased activity of the key enzymes of delipidation of lipoprotein particles (LPL, HTGL) and of HDL remodeling (LCAT). In epidemiological studies no correlation has been found in dialysis patients between total lipids and atherosclerotic endpoints and a modest relation, at best, between more sophisticated apolipoprotein indices and vascular disease. Such lack of correlations are presumably explained by malnutrition as a confounding factor. Fascinating new observations in animal studies document that in various models of renal damage, development of glomerulosclerosis is accelerated by hyperlipoproteinemia, either endogenous hyperlipoproteinemia or hyperlipoproteinemia induced by feeding of fat. Conversely, correction of hyperlipoproteinemia mitigates development of glomerulosclerosis. Currently there is no firm evidence that the same is true in humans.

The determination of total cholesterol (and eventually triglycerides) is sufficient for screening purposes. Values below 5.2 mmol/l (200 mg/dl) may be considered ideal, where as higher values need a differentiated diagnostic evaluation which should include the measurement of triglycerides and of HDL-cholesterol after 12 h fasting. The decision for a drug therapy should consider other risk factors such as hypertension, smoking, diabetes mellitus, male sex, positive family anamnesis for myocardial infarction already existing and coronary heart disease. The treatment of a dyslipoproteinemia should always start with dietary measures. If these are not successful, a lipid-regulating drug therapy should be started in addition to the diet. The choice of the drug depends on the type of dyslipoproteinemia and its genetic and metabolic cause and on the individual side effects.

A review of the literature confirms a regular and significant lowering of serum triglycerides by omega-3 fatty acids. This effect is the more pronounced the higher the initial levels are. Accordingly, in type V hyperlipoproteinemia, it is particularly marked. In normolipemic subjects and in patients with hypercholesterolemia (type IIA), total cholesterol is only slightly reduced. In patients with elevation of cholesterol and triglycerides (types IIB, IV and V), both triglycerides and cholesterol are lowered. This decrease is mainly obtained by reduction in VLDL cholesterol. In the case of types IV and V, on the other hand, triglyceride reduction is associated with an elevation of LDL and HDL cholesterol. At present, it is not clear whether the increase in LDL cholesterol is of a transient nature and prognostically irrelevant. It can be prevented by reducing the intake of saturated fat. HDL cholesterol is decreased by high doses and increased by low doses of omega-3 fatty acids. In the differential treatment of hyperlipoproteinemias, consideration should be given to these points.

Accelerated coronary atherosclerosis is a common complication following coronary angioplasty, coronary venous bypass grafting, and heart transplantation. Since dyslipoproteinemias are a major risk for atherosclerotic lesions, a consequent and effective lipid-regulating treatment is mandatory in these patients. The CLAS-findings are an impressive documentation for the beneficial effects of a substantial lipid-regulating treatment on progression and even repression of atherosclerosis.

10 patients with hyperlipoproteinaemia and 4 normolipaemic smokers with angiographically proved arteriosclerosis of different degrees of severity were infused in 2-week intervals 100 ml HDL-rich Cohn-IV-1 fractions each. After the infusion for 5 days essential phospholipids were injected and a permanent medication with cholestyramin and a choleretic drug were prescribed. In the patients with HLP increases of concentration, decreases of concentration, constancy of the plasma lipids and apoproteins independent of the phaenotype of the HLP as well as an improvement of the state of the antioxidant state were observed. In 6 of 10 patients in reproducible vascular areas regressions of athero- und arteriosclerotic findings could be made evident. Progressions were not observed also in extremely changed arteries in contrast to the normolipaemic smokers and the patients of the control group.

By reason of their frequency and complications hyperlipoproteinaemias increasingly get importance for the intensive medicine. When a hypertriglyceridaemia is present one must be particularly careful in the supply of lipid emulsions and monosaccharides. The choice of suitable infusion solutions can in every case be derived only from the etiopathogenesis of the lipid increase. In general is valid that these patients have an increased cardiovascular risk, inclination to disturbances of the cardiac rhythm, thrombembolies, diabetes and pancreatitis.

Combined treatment of hyperlipidaemia with a 1000-calorie-diet and d-triiodothyronine resulted in a lowering of serum cholesterol, triglycerids and lipoproteins. Concerning cholesterol and beta-lipoproteins there was an addition of reducing effects of simultaneous dietary and drug treatment. Triglycerids are influenced by the combined treatment or by dietary treatment alone to the same extent. The levels of free fatty acids rise during combined treatment while there is no change by diet alone. These observations indicate a most successful lowering of cholesterol and beta-lipoproteins by the combined therapy, but there is an increase of free fatty acids as a metabolic side effect of d-triiodothyronine.

By means of the modified Cohn-method 6 Cohn-IV-1-fractions were prepared in the small pool technique as sterile, pyrogen-free and HDL-rich serum fractions (HDLF), the HDL-concentrations of which were 15-20 g/l. In in-vitro investigations they inhibited the spontaneous aggregation of erythrocytes as well as the ADP-induced aggregation of thrombocytes and activated the molar and fractional initial cholesterol estirification rates as well as the prostacyclin synthesis. From HDLF intravenously applied in people as immediate effects result significant decreases of the cardiac pre- and afterload, an increase of the cardiac ejection fraction as well as a complete dissolution of circulating aggregates of thrombocytes. In 35 patients with hyperlipidaemias after infusion of 100 ml HDLF up to the 5th day increasing and for 14 days remaining increases of concentration of biliary bile acids, total phospholipids and of cholesterol were observed in lithogenic indices remaining in the normal region. The plasmatic lipo- and apolipoproteins reacted with increases, decreases or constancy of concentration which might be based on the different ethryopathogeneses of the hyperlipoproteinaemias.

Secondary hyperlipoproteinemias frequently occur in patients with conservatively treated chronic uremia, under hemodialysis, after renal transplantation and notably in patients with the nephrotic syndrome. In chronic uremia patients conservatively treated or under hemodialysis, hypertriglyceridemia (type IV-pattern) is predominant whereas after renal transplantation and in the nephrotic syndrome hypercholesterolemia (type II-pattern) is more frequent. With the exception of hyperlipoproteinemia in the nephrotic syndrome, these hyperlipoproteinemias are associated with markedly reduced levels of the protective HDL. They therefore represent a relevant atherogenic risk. Lipoprotein disorders in chronic uremia are mainly due to disturbed catabolism of triglyceride-rich lipoproteins; treatment with corticosteroids may be the major underlying pathogenic mechanism of hyperlipoproteinemia after renal transplantation, whereas in the nephrotic syndrome increased hepatic lipoprotein production is observed.

141 children and adolescents (7-21 years, mean age 14.2 years) showed values of blood pressure, total cholesterol and triglycerides greater than or equal to 90 percentile and HDL-cholesterol values less than or equal to 10 during an examination of 639 children of parents with distinct coronary risk factors or early percentile infarction. By randomization they were subdivided into two groups. (A and B) and underwent intervention measures of different intensity. While group B got only a unique recommendation concerning the preventive measures, in group A a regular, non medicamentous individual treatment was performed. After one year a decrease of blood pressure could be proved in the two groups. A significant decrease of total and HDL cholesterol was found only in group A. While the blood pressure was most clearly reduced in 7-13-year-old children, the most distinct lipid changes were shown in 14-17-year-old adolescents. An influence on body-weight and triglycerides could not be established. Our results confirm the possibilities and also the limits of preventive measures in childhood and adolescence. Apart from the intended decrease of blood pressure and total cholesterol the simultaneous decrease of HDL-cholesterol refers to open questions in the conception of the primary prevention, particularly in children.

For the prevention and therapy of metabolic and cardiovascular diseases every internal specialist needs basic knowledge of a rational diagnostics of lipids. The basic analytics of lipids must take into consideration (as to computation) total cholesterol, HDL cholesterol, triglycerides and LDL cholesterol. According to the newest publications of the European Society for Atherosclerosis is orientated to a total cholesterol of 5.2 mmol/l and to triglycerides of 2.3 mmol/l, in order to keep the character of the atherogenic risk as insignificant as possible.

On the basis of an extensive study of references as well as of own experiences the present state of the plasma exchange therapy, its success, problems and tendencies are represented. In the 1st part the essential modifications of the technique (plasmapheresis/plasma filtration), problems of anticoagulation, kind and quantity of the substitution as well as tendencies to more specific separation methods are explained. The 2nd part gives a survey of all essential indications (Goodpasture's syndrome, myasthenia gravis, hyperviscosity syndrome, lupus erythematodes visceralis, intoxications) and shows the main complications.

Metabolic and clinical effects of an original electromyostimulation are explained which induces muscle contractions by changes of the field intensity in the region of microseconds in forms of delivered impulse groups. On account of the good local compatibility due to optimal irritation parameters the muscle stimulator was suitable for a long-term application. Examinations on 23 patients with hyperlipoproteinaemia and mixed HLP (n = 15) and primary hypercholesterolaemia (n = 8) after a 2 times 2 hours/day mutual stimulation of the femoral musculature in a frequency of 2 s-1 lasting four weeks yielded a significant decrease of the triglyceride and cholesterol concentrations as well as an increase of the HDL-cholesterol in mixed HLP-forms. Examinations not yet finished refer to an increase of the extrahepatic activity of the postheparin-lipoprotein lipase and to the concentration of the HDL2-cholesterol. An influence of the hypercholesterolaemia IIa could not be made evident. An electrostimulation performed for 3 months in 8 patients with obliterating arteriosclerosis resulted in a more sufficient collateral blood supply of the legs. The long-term use of the device was unobjectionable also under ambulatory conditions. On the basis of additionally gathered experiences further indications of an electrostimulation were cited. Possible variations of the electrostimulation irritation parameters might make accessible further fields for the preventive and curative medicine.