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Biomedical subjects

H Stolte

Publications and source records attributed to H Stolte.

At least 55 records · Page 3Linked to original sources

Heterogeneity of glomerular barrier function in early adriamycin nephrosis of MWF rats.

Adriamycin (ADR), selectively toxic to glomerular epithelial cells, was administered (5 mg/kg BW, i.v.) to MWF/Ztm rats to study its early effects on glomerular barrier function with respect to albumin and high molecular weight (HMW) proteins. After 7 days of ADR incubation (glomerular filtration rate remains unchanged), protein excretion was significantly increased in treated rats. The proteinuria was due to a nonselective glomerular lesions resulting in an increase in both, but not a changed ratio of HMW proteins to albumin. However, this ADR-induced proteinuria seen in the final urine was not confirmed by free-flow micropuncture studies of superficial glomeruli. The albumin and HMW protein concentrations in samples taken from Bowman's capsular space of ADR-treated rats did not significantly differ from control samples. These data suggest that cortical nephrons are less sensitive to ADR than juxtamedullary nephrons.

Albuminuria↗

Adaptation of renal function to hypotonic medium in the winter flounder (Pseudopleuronectes americanus).

The kidneys of winter flounders transferred to hypotonic medium were investigated for glomerular and tubular handling of fluid and electrolytes and for the urinary excretion of proteins. Media were sea water (925 mosm X kg-1) and brackish water (70 mosm X kg-1). In sea water, the urine was hypertonic to the plasma in 7 fish of this study. Urine flow rate was correlated with the GFR. After adaptation to brackish water a delay of 1 to 3 days was observed until the kidneys switched from fluid retention to the excretion of large amounts of dilute urine. GFR and urine flow rate were increased from 0.61 +/- 0.08 to 1.58 +/- 0.29 ml X h-1 X kg-1 and from 0.14 +/- 0.02 to 0.68 +/- 0.08 ml X h-1 X kg-1, respectively (mean +/- SEM). With increased filtered load the tubular reabsorption of fluid decreased from 74 +/- 2.4% to 45 +/- 11.2%. The excretion rates of sodium and potassium were increased due to decreased fractional sodium and potassium reabsorption. The urinary excretion of divalent cations, however, was reduced because the net tubular reabsorption of calcium was increased and the net secretion of magnesium was diminished. Both the urinary total protein concentration and the protein pattern showed no significant change, but the rate of protein excretion was increased from 0.21 +/- 0.04 to 0.60 +/- 0.05 mg X h-1 X kg-1. The comparison of protein patterns obtained from urine and serum samples revealed that high molecular weight (HMW) proteins prevail in the serum whereas low molecular weight (LMW) proteins dominate in the urine. The diminished quantity of the HMW-protein fraction in the urine thus may reflect size selectivity of the glomerular filtration barrier for serum proteins also in the winter flounder.

Adaptation, Physiological↗

Single nephron hyperfiltration and proteinuria in a newly selected rat strain with superficial glomeruli.

Alterations in glomerular permeability were studied in female MWF/Ztm rats, newly selected from the Munich Wistar rats with a high number of superficial glomeruli. This strain is characterized by a diminished number of functioning nephrons, an elevated arterial blood pressure and a high proteinuria averaging 24 mg/24 h. Samples of Bowman capsular space (BCS) obtained by free-flow renal micropuncture techniques with pressure control were analyzed for albumin and high-molecular-weight (HMW) proteins by ultramicrodisc electrophoresis. The measured mean albumin and HMW protein concentration in BCS were 1.72 g/l and 0.66 g/l, respectively. The glomerular filtration rate (GFR) averaged 0.74 ml/min/g kidney weight and the single nephron GFR (SNGFR) 48 nl/min. Ultrastructural studies revealed focal bleb-like alterations of the podocytes as has been observed in hyperfiltration states. We suggest that the reduced number of functioning nephrons in the kidneys of these rats could induce glomerular hyperfiltration and permselectivity changes, which cause a high glomerular protein leakage.

Animals↗

Early changes in renal function following chemically induced nephropathy.

The functional changes in the rat kidney 24 h after administration of 2-bromoethanamine hydrobromide (BEA) have been extensively described. There is, however, little information regarding earlier alterations. The present study was designed to measure early changes in renal function in order to clarify further pathomechanisms of the BEA-induced lesion. Experiments were performed in two groups of Wistar rats with different infusion rates during the first 3 h following injection of 100 mg/kg BW BEA compared to sham-injected rats. Analysis included measuring urine flow, osmolality, urea, sodium and potassium as well as inulin and para-aminohippuric acid clearance. Our studies show a tubular as well as a glomerular involvement in BEA-induced nephropathy. A significantly higher urine flow occurred already in the first 30 min following injection of BEA. Urine osmolality began to decrease after 90 min, Na excretion was elevated at 3 h, K excretion was not significantly different from the control group, urea excretion was increased after 30 min. Contrary to other studies we found a continuously decreasing glomerular filtration rate and PAH clearance during the first 3 h. Our results suggest an early effect of BEA on tubular function (increasing sodium excretion), papillary concentration capacity (increasing urine flow combined with decreasing osmolality) and glomerular function (decreasing glomerular filtration rate).

Animals↗

Glomerular albumin leakage and morphology after neutralization of polyanions. II. Discrepancy of protamine induced albuminuria and fine structure of the glomerular filtration barrier.

Changes in the fine structure of the glomerular filtration barrier were studied by perfusion of isolated rat kidneys with varying doses of protamine: 1) at low doses (110-150 micrograms/ml) ultrastructural changes were only detectable after prolonged recirculation (90-120'), 2) at high doses (250-330 micrograms/ml) profound epithelial foot process lesions were observed even after a short perfusion time, 3) at any concentration protamine particles were distributed in the laminae rarae of the GBM, thus visualizing neutralization of fixed negative charges. Reduction of glomerular anionic sites caused pronounced albuminuria even before podocyte morphological alterations were detectable. The effects of protamine on structure and function of the glomerular capillary wall are dose and time dependent. Besides intact morphology of the epithelial cells regular distribution of negative charges is necessary to maintain glomerular barrier function to macromolecules. Foot process alterations are not the primary reason for increased proteinuria but rather a secondary phenomenon.

Albuminuria↗

Glomerular albumin leakage and morphology after neutralization of polyanions. I. Albumin clearance and sieving coefficient in the isolated perfused rat kidney.

In order to decide whether foot process abnormalities in nephrotic states are the cause or the consequence of proteinuria, the polycation protamine has been applied to isolated perfused rat kidneys and functional parameters and morphology have been compared. With 110 micrograms/ml protamine the albumin clearance ratio increased from 2.0 +/- 0.7 x 10(-3) in controls to 14.8 +/- 6.9 x 10(-3) 10-20 min after application and even to 98.0 +/- 30.8 x 10(-3) after 50-80 min. Micropuncture samples collected from early proximal tubules with pressure control were used to calculate the sieving coefficient which correlated with albumin clearance ratios (controls: 1.8 +/- 1.0 x 10(-3); after 10-20 min: 11.8 +/- 6.4 x 10(-3); after 50-80 min: 52.0 +/- 8.5 x 10(-3). Glomerular filtration rate decreased in the early beginning from 1.1 +/- 0.2 ml x min-1 x g-1 kidney to 0.7 +/- 0.2 ml x min-1 x g-1 kidney, but remained constant throughout the whole experiment. Despite the markedly increased albuminuria there were no changes in glomerular foot process morphology with the protamine dose used.

Albumins↗

Nephrotoxicity of cis-diamminedichloroplatinum with or without ifosfamide in cancer treatment.

cis-Diamminedichloroplatinum (DDP) and ifosfamide (IPP) are effective cytostatic agents with a considerable nephrotoxicity. Because of the known synergism of both drugs in animals the combination has been studied in man with disseminated testicular cancer. Nature and extent of nephrotoxicity of DDP in combination with vinblastine, bleomycin and with or without IPP was investigated. The renal involvement was studied during volume expansion and mannitol diuresis. In addition to total kidney function (creatinine clearance and renal electrolyte handling), tubular function has been determined by quantitative assessment of urinary albumin, beta 2-microglobulin, maltase and leucine aminopeptidase excretion. The urinary protein pattern was also analyzed by microgradient electrophoresis to determine low and high molecular weight proteins. The total protein excretion was raised in the groups of patients with DDP and IPP to a 5-fold of the normal (976 +/- 96 mg/24 h) versus a 4-fold increase (756 +/- 102 mg/24 h) without IPP. This was mainly due to renal tubular involvement. For example, IPP raised the tubular toxicity induced by DDP considerably with a 200-fold increase of the beta 2-microglobulin excretion versus only a 10-fold increase without IPP (p less than 0.02). All lesions were reversible and caused no lasting impairment of kidney function. It is concluded that combination regimens including DDP and IPP can be used without a major risk of acute or chronic renal insufficiency. However, urinary protein excretion should be monitored to make certain that the tubular function improves between or after the treatment courses.

Albuminuria↗

Renal handling of uremic middle molecules. a study with the isolated perfused rat kidney.

Little is known of the normal renal handling of potential uremic toxins in the middle molecular weight (MMW) range (300-2,000 daltons). In this study the isolated rat kidney has been used as a model to investigate renal clearance and possible renal metabolic effects on uremic MMW species. Isolated rat kidneys were perfused with hemofiltrate from chronic renal failure patients containing 5% bovine albumin. Middle molecules (MM) were isolated from perfusates and urines by high-speed gel filtration (peak 7) and further separated by gradient elution chromatography to give 7-8 definable uremic MMW species (7a, b, c, etc.). Species 7b, d, e and f were tubularly reabsorbed by 15, 25, 23 and 34%, respectively, as indicated by simultaneous inulin clearances. 7a was freely filtered with negligible reabsorption. 1 MM (7c1) was found to be secreted by up to 220% at low perfusate concentrations, secretion being masked at high perfusate levels. No MMs were catabolized by the kidney, although one species (7c2) appeared to be synthesized. The results suggest that uremic MMs have differing biological or physicochemical activities as indicated by the selectivity of renal handling.

Animals↗

Middle molecules in patients with pre-dialysis chronic renal failure: a comparative clearance study.

Residual renal function is an important parameter int he design of dialysis regimens. In this study residual renal clearance of potential uremic toxins in the middle molecular weight range (originally thought to be 300-2000 daltons, but now considered close to 300-700 daltons) was investigated in patients with predialysis chronic renal failure. Middle molecules were isolated from uremic sera and urines by gel filtration and further separated by gradient elution chromatography to give 7 to 8 definable uremic middle molecular weight species. The renal clearances of middle molecule fractions were compared with simultaneously measured endogenous creatinine, urinary inulin and single short inulin clearance. The four middle molecule fractions which were quantitated (7a, b, c and d) were found to be freely filtered and to have renal clearances in end stage renal failure approximately equal to the endogenous creatinine clearance. Thus, renal handling of middle molecules is strikingly different from that of other peptides of peptide hormones in that the species do not appear to be catabolized, secreted or reabsorbed by the renal tubules to any significant degree.

Aged↗

Glomerular basement membrane and mesangial matrix: a comparative study in different vertebrates.

Perfusion fixation of the rat kidneys with aldehydes and alcian blue demonstrates within the glomerular mesangium various components displaying anionic binding sites. These are the surface coat of the mesangial cells, numerous mesangial microfibrils (probably glycoproteins), and polygonal particles (Presumably proteoglycans). These particles lie close to the mesangial cells and form assemblies of various extension within the mesangial matrix as well. In addition, a discontinuous basement membrane can be recognized which surrounds the mesangial cells. In the hagfish glomeruli (fixed without cationic dye), a prominent layer of microfibrils is interposed between mesangial and endothelial cells. Both these cells show incomplete basement membranes.

Animals↗

Renal handling of middle molecules in uremic patients and in the isolated rat kidney.

Renal handling of uremic middle molecules (MW 300-2000 daltons) was investigated (1) in the diseased kidney in nine patients suffering from chronic renal failure in the pre-dialysis phase, and (2) in the isolated perfused rat kidney using hemofiltrate and albumin (5 gm/100 ml) containing perfusate. Middle molecules clearances are compared to the simultaneously measured inulin and creatinine clearances. Four middle molecule fractions (peak 7a, 7b, 7c, and 7d) were quantitated after high-speed gel filtration and gradient elution chromatography and found to be freely filtered (= middle molecules clearances not differing from inulin and creatinine clearances) in uremia in man. In the "intact" (isolated perfused) rat kidney, elimination also takes place by glomerular filtration (peak 7a, 7c at high perfusate levels). Peaks 7b and 7d are slightly reabsorbed (15% and 25%, respectively, of filtered load), whereas 7c1 is secreted up to 220% of inulin clearance at low perfusate levels. No renal catabolism and high urinary excretion of middle molecules clearly indicate different renal handling of this species in comparison to other peptides or peptide hormones of the same molecular weight range.

Aged↗