Clemens Grupp

Retrospective Analysis of Long‐term Lipid Apheresis at a Single Center

We retrospectively analyzed 10 906 lipid apheresis sessions (heparin‐induced lipoprotein precipitation, direct adsorption of lipoproteins, double filtration plasmapheresis, dextran sulfate adsorption, and immunoadsorption) in 38 patients who were consecutively treated in our department during the last 20 years. The incidences of major cardiovascular events (MACE) (death, cerebrovascular accident, myocardial infarction, limb amputation, and renal vascular involvement) were taken separately as primary end‐points or as a combined end‐point. The time‐course of secondary end‐points (coronary and extracranial status of arteries, left ventricular function, occlusive artery disease, and calculated glomerular filtration rate [cGFR]) were also evaluated, as well as the extent of the reduction in plasma lipids and lipoproteins and the incidence of therapy associated side‐effects. MACE decreased from 7.02% events per patient per year at the start of lipid apheresis to 1.17% during lipid apheresis and the rate of myocardial revascularization decreased from 22.8% to 3.8% per patient per year. Classical (diabetes mellitus, arterial hypertension, and smoking history), as well as novel risk factors (cGFR < 60 mL/min, statin withdrawal, mixed hyperlipoproteinemia, and elevated lipoprotein (a)) were associated with an elevated risk for MACE. All applied methods had comparable effects. All lipid apheresis methods proved to be safe and suitable for long‐term treatment. The present data demonstrate that treatment with lipid apheresis is very effective and leads to long‐term reduction in cardiovascular mortality and morbidity. 

Measurement of element content in isolated papillary collecting duct cells by electron probe microanalysis

A method was developed to measure the element content of freshly isolated papillary collecting duct (PCD) cells by electron probe microanalysis in a scanning electron microscope. After isolation, the cells were transferred onto a Thermanox support by centrifugation and the extracellular medium was removed by brief exposure to buffered ammonium acetate; cryofixation, freeze-drying, and coating with carbon followed. Under visual control in the scanning electron microscope the Na, Cl, K and P content of cell clusters (about 30 cells/cluster) was then measured by X-ray microanalysis. Cells incubated in control medium showed potassium: sodium ratios identical to those determined previously in cryosections of the same cells. In ouabain-treated cells sodium influx and potassium efflux was demonstrated. Potassium left the cells with at1/2 of 21.7 min. Thet1/2 of Na influx was 12.6 min for the first 15 min of incubation, whereafter further influx was markedly slower. Ouabain-induced sodium influx was inhibited 40% by amiloride. These results indicate that X-ray microanalysis can be applied to analyze the ion content of isolated cell clusters derived from the papillary collecting duct. Using ouabain and amiloride as inhibitors the suitability of the method to identify transport systems is demonstrated.

Difference between renal and splenic resistive index as a novel criterion in Doppler evaluation of renal artery stenosis

Detection of renal artery stenosis (RAS) using Doppler is difficult to evaluate, particularly under conditions such as bilateral RAS or difficultly accessible renal arteries (RA). The objective of the present study was to assess the utility of splenic arterial compared to renal flow as an additional parameter in the Doppler evaluation of RAS. The difference between the resistive indices (RI) determined in renal and splenic parenchymal arteries (ΔRIK−S) was evaluated in 181 hypertensive subjects without any evidence of RAS. Subsequently 47 RA in 24 patients with suspected RAS were angiographically assessed. A ΔRIK−S of 0.055 (median) was determined in the population without any evidence of RAS similar to RA with angiographically excluded stenosis (ΔRIK−S 0.068). In contrast, in angiographic proven RAS, ΔRIK−S was significantly lower (−0.050; P < .005). The assessment of the ΔRIK−S, proved to be an easily feasible parameter, which improves the diagnostic accuracy in the detection of RAS.

Transmembrane transport and intracellular metabolism of papillary cells

Taking into account recent results obtained with isolated papillary collecting duct cells the metabolic pathways and membrane transport systems of collecting duct cells are reviewed. The plasma membranes contain a luminal proton AT-Pase and a contraluminal Cl−/HCO 3 − exchanger which are involved in proton secretion; a luminal sodium channel and a contraluminal Na+/K+-AT-Pase for sodium reabsorption; a K+ channel for potassium secretion, and a Na+/K+/Cl− cotransport system for chloride transport and/or volume regulation. The plasma membranes also possess transport systems for organic substrates and organic osmolytes. D-glucose, the main substrate of the papillary collecting duct is taken up into the cell by a sodium-independent D-glucose transport system with aK m of 1.2 mM. The plasma membrane also contains mechanisms which mediate sorbitol release into the medium. This mechanism is stimulated when cells are exposed to media with a low osmolality and inhibited when cells are exposed to media with a high osmolality.SummaryTaking into account recent results obtained with isolated papillary collecting duct cells the metabolic pathways and membrane transport systems of collecting duct cells are reviewed. The plasma membranes contain a luminal proton AT-Pase and a contraluminal Cl−/HCO3− exchanger which are involved in proton secretion; a luminal sodium channel and a contraluminal Na+/K+-AT-Pase for sodium reabsorption; a K+ channel for potassium secretion, and a Na+/K+/Cl− cotransport system for chloride transport and/or volume regulation. The plasma membranes also possess transport systems for organic substrates and organic osmolytes. D-glucose, the main substrate of the papillary collecting duct is taken up into the cell by a sodium-independent D-glucose transport system with aKm of 1.2 mM. The plasma membrane also contains mechanisms which mediate sorbitol release into the medium. This mechanism is stimulated when cells are exposed to media with a low osmolality and inhibited when cells are exposed to media with a high osmolality.D-glucose is used as metabolic substrate in anaerobic and aerobic glycolysis and as precursor for sorbitol synthesis via the aldose reductase, which is highly enriched in papillary collecting duct cells. The cells also show gluconeogenic activity as evidenced by incorporation of labeled carbon from L-alanine into glycerol, sorbitol, and myo-inositol. Accordingly, the cells show fructose-1,6-biphosphatase activity. Sorbitol synthesis in contrast to sorbitol permeability is not affected by osmolarity.These studies indicate that transmembrane transport and intracellular metabolism of papillary cells strongly depend on the composition of the interstitium and show a plasticity which allows the cells to cope successfully with the metabolic and osmotic challenges connected with urine concentration or dilution.Taking into account recent results obtained with isolated papillary collecting duct cells the metabolic pathways and membrane transport systems of collecting duct cells are reviewed. The plasma membranes contain a luminal proton AT-Pase and a contraluminal Cl-/HCO3- exchanger which are involved in proton secretion; a luminal sodium channel and a contraluminal Na+/K+-AT-Pase for sodium reabsorption; a K+ channel for potassium secretion, and a Na+/K+/Cl- cotransport system for chloride transport and/or volume regulation. The plasma membranes also possess transport systems for organic substrates and organic osmolytes. D-glucose, the main substrate of the papillary collecting duct is taken up into the cell by a sodium-independent D-glucose transport system with a Km of 1.2 mM. The plasma membrane also contains mechanisms which mediate sorbitol release into the medium. This mechanism is stimulated when cells are exposed to media with a low osmolality and inhibited when cells are exposed to media with a high osmolality. D-glucose is used as metabolic substrate in anaerobic and aerobic glycolysis and as precursor for sorbitol synthesis via the aldose reductase, which is highly enriched in papillary collecting duct cells. The cells also show gluconeogenic activity as evidenced by incorporation of labeled carbon from L-alanine into glycerol, sorbitol, and myo-inositol. Accordingly, the cells show fructose-1,6-biphosphatase activity. Sorbitol synthesis in contrast to sorbitol permeability is not affected by osmolarity.(ABSTRACT TRUNCATED AT 250 WORDS)

Untersuchung der Nierenfunktion mit Hilfe isolierter Zellen

SummaryAfter summarizing the progress which has been made with regard to the isolation and characterization of homogeneous cell populations from the kidney, a brief survey of current techniques available for the analysis of intracellular parameters is given. Special emphasis is thereby placed on the use of electron probe X-ray microanalysis to determine intracellular elements and on „in vivo“ nuclear magnetic resonance to define metabolic pathways in isolated cells. These methods have been applied to study ion and substrate fluxes in isolated collecting duct cells and the response of these cells to changes in osmolality of the extracellular medium. This response involves initially fast water movements accompanied by changes in intracellular sodium and chloride but not potassium concentration. Longterm adaptation is achieved by the adjustment of the intracellular concentration of „organic osmolytes“ such as sorbitol, myoinositol, glycerophosphorylcholine, and betaine through changes in the rate of efflux of these metabolites from the cell. In the last section the effect of experimentally induced diabetes mellitus on the osmoregulation in isolated collecting ducts is described.

Die tubulointerstitielle Nephritis (medikamentös/infektiös)

Bei der akuten Form der tubulointerstitiellen Nephritis (TIN) sind meist allergische Reaktionen auf Medikamente die Ursache, neben Antibiotika zunehmend auch Protonenpumpenhemmer. Bei den infektiösen Formen war zuletzt eine Zunahme von Hanta-Virus-Infektionen zu beobachten. Relativ neu beschrieben ist die IgG4-assoziierte Form. Eine definitive Diagnose der TIN ist nur mittels Nierenbiopsie möglich. Diese wird selten gewonnen, sodass von einer hohen Dunkelziffer auszugehen ist. Die IgG4-assoziierte Form weist spezifische histologische Veränderungen auf. Essenziell ist eine sorgfältige Anamnese. Laborchemisch typisch, aber wenig spezifisch ist ein Anstieg der Retentionsparameter bei geringgradiger Proteinurie und nicht glomerulärer Hämaturie. Definitiv gesicherte Marker für das Vorliegen einer TIN sind bislang nicht validiert. Die wichtigste therapeutische Maßnahme besteht im Ausschalten eines potenziellen Auslösers. Medikamentöse Therapie der ersten Wahl sind Glukokortikoide, obgleich die studienbasierte Evidenz sehr schmal ist und überwiegend auf älteren Daten beruht.

Bluthochdruck – Der hypertensive Notfall

Hypertensive crisis and hypertensive emergency are characterized by an imminent or apparent organ damage (cerebral, cardial, renal etc.) associated with an acute increase of the arterial blood pressure (usually systolic > 180 mmHg and/or diastolic > 120 mmHg). It represents an emergency which requires immediate therapeutic intervention. Drugs of choice for the initial therapy prior to hospitalization are nitroglycerine, nitrendipine, clonidine and urapidil. Further therapy realigns on the predominant clinical symptoms and signs as well as on the cases and reasons of the elevated arterial pressure. If arterial hypertension is not already clarified, this should be done after stabilization of the blood pressure.