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H Stolte

Publications and source records attributed to H Stolte.

95 records · Page 6Linked to original sources

Filtration characteristics of the single isolated perfused glomerulus of Myxine glutinosa.

Using an in vitro microperfusion technique, the filtration characteristics of single isolated glomeruli of the Atlantic hagfish (Myxine glutinosa) were investigated. The suitability of the method as a model to study glomerular function was evaluated. Experiments with a protein-free perfusate led to a filtration coefficient Kf (0.189 +/- 0.181 nl x s-1 x mm Hg-1) that was in the same order of magnitude as determined in vitro for other vertebrates. Morphometric analysis on serial thin sections (1 microns) revealed a glomerular capillary surface (A) of 1.84 +/- 0.72 mm2. A linear relationship between glomerular diameter and A allowed the calculation of the hydraulic conductivity Lp (0.618 +/- 0.384 microliter x s-1 x mmHg-1 x cm-2). The data indicate that the isolated perfused glomerulus of M. glutinosa has filtration characteristics similar to higher vertebrates. The glomeruli of M. glutinosa, which in contrast to glomeruli of other animals are easy to dissect, are a suitable model for the study of glomerular filtration and permeability characteristics of vertebrates. An example of a possible application of the model is a study into the effects of adrenaline on glomerular filtration characteristics. Adrenaline led to increases in ultrafiltration pressure (PUF), single nephron glomerular filtration rate (SNGFR) and filtration fraction (FF); Kf remained unaffected.

Animals↗

Cathepsin B and L in isolated proximal tubular segments during acute and chronic proteinuria.

Acute and chronic proteinuria were studied in rats, using lysosomal cathepsin B and L as marker enzymes for tubular protein degradation. The activity of cathepsin B and L has been determined in microdissected segments S1, S2 and S3 of the proximal tubule by an ultramicroassay. Z-Phenylalanyl-arginine-7-amido-4-methylcoumarin served as a substrate. In normoproteinuric Sprague-Dawley rats, induction of acute unselective glomerular proteinuria with Adriamycin (5 mg/kg body weight) revealed a moderate activity increase of cathepsin B and L in the S2 segment, reaching 12.6 +/- 5.6 versus 8.6 +/- 4.2 pmol.mm-1.min-1 in controls. In contrast, Munich Wistar Frömter (MWF) rats, that are characterized by a genetically determined, chronically elevated glomerular protein excretion, showed a very high activity of cathepsin selectively in S2 of 25.0 +/- 12.1 pmol.mm-1.min-1. Acute proteinuria induced by Adriamycin in chronic proteinuric MWF rats could increase cathepsin activity in the S3 segment only, showing 12.0 +/- 8.3 versus 6.8 +/- 4.0 pmol.mm-1.min-1 in MWF control rats. In conclusion, chronically increased protein filtration changes the functional reserve capacity of the proximal tubule. While acutely induced glomerular proteinuria in normoproteinuric rats stimulates lysosomal proteolytic activity mainly in S2 segment, chronic proteinuric MWF rats may display already a maximally stimulated cathepsin activity in this segment probably due to long-term increased tubular protein load. In case of acute elevation of chronic proteinuria, the consecutive S3 segment shows increased lysosomal function for protein conservation.

Acute Disease↗

Evaluation of late nephrotoxicity in long-term survivors of Hodgkin's disease.

Chemotherapy (Ctx) and/or radiotherapy (Rtx) are effective in the treatment of Hodgkin's disease (HD) but potentially involve late toxicities, including nephrotoxic side effects. Therefore a follow-up study has been performed to screen patients for late signs of an impaired tubular or glomerular function and to correlate data of renal function with type of therapy and cumulative doses of cytotoxic agents applied. 81 patients in complete remission for at least 2 years and a median follow-up of 96 (39-304) months, and 53 controls were examined. Clinical routine parameters such as creatinine and electrolytes were determined. A differentiation of proteinuria into the albumin, high molecular weight (HMW) and low molecular weight (LMW) fractions made it possible to assess glomerular and tubular function based on the LMW/HMW ratio. The structural protein fibronectin served as an additional, sensitive marker of glomerular integrity. Routine parameters of kidney function did not show any signs of late nephrotoxicity. However, patients treated for HD had a higher ratio of LMW/HMW in comparison to the group of healthy volunteers (p < 0.01), indicating subclinical tubular renal damage. When the cutoff for tubular damage was defined as LMW/HMW > 1.5, 50% of the patients treated with combined modality, and 42 and 37% of the patients with Ctx or Rtx alone had subclinical tubular alterations, respectively. A tendency towards a higher prevalence of subclinical tubular changes was observed in patients with higher cumulative doses of methotrexate or ifosfamide and in patients with combined Ctx and Rtx with radiation fields involving the renal area. Changes in glomerular function were not observed. It is concluded that treatment of HD is not associated with clinically apparent long-term impairment of renal function but can lead to subclinical alterations. Further clinical implications of these subclinical tubular alterations cannot be assessed at present. A differentiation of proteinuria does not have to be performed routinely but might be useful in the follow-up of selected patients with an increased risk.

Adult↗

Comparative study of the acute nephrotoxicity from standard dose cisplatin +/- ifosfamide and high-dose chemotherapy with carboplatin and ifosfamide.

The nephrotoxic effects of different platinum compounds based combination chemotherapies were compared. Chemotherapy consisted of either cisplatin fractionated over 5 days (5 x 20 mg/m2) or given as a single-day infusion (1 x 50 mg/m2) plus ifosfamide (4 g/m2) or high-dose chemotherapy was applied including carboplatin (3 x 500 mg/m2) and ifosfamide (3 x 4 g/m2) fractionated over three consecutive days. Conventional parameters such as serum creatinine and glomerular filtration rate (GFR), as well as urinary protein excretion of N-acetyl-beta-D-glucosaminidase (NAG)) and alpha 1-micro-globulin were assessed in 52 patients. Fractionation over 5 days without adding other nephrotoxic agents, i.e. ifosfamide, prevented decreases in GFR following cisplatin, whereas the combination of conventional dose cisplatin and ifosfamide, given as a single-day infusion, and high-dose carboplatin/ifosfamide yielded a pronounced fall of GFR. All groups showed increases in the urinary excretion levels of serum derived proteins and NAG, but with significant differences; about 2 to 3-fold for 5-days cisplatin, 3 to 5-fold for single-day cisplatin/ifosfamide, and 20 to 35-fold for high-dose chemotherapy. Thus, conventional approaches can reduce but not prevent the nephrotoxicity of cisplatin-based chemotherapy. In particular, high-dose chemotherapy regimens including carboplatin and ifosfamide are associated with comparable or even higher nephrotoxicity to single-day cisplatin/ifosfamide. In the light of the long-term consequences of persistent renal damage prevention of nephrotoxicity should be further improved.

Acetylglucosaminidase↗