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Renal handling of radiolabelled human cystatin C in the rat

Tenstad, O ; Roald, A B ; Grubb, A LU orcid and Aukland, K (1996) In Scandinavian Journal of Clinical and Laboratory Investigation 56(5). p.409-414
Abstract

Serum cystatin C concentration correlates negatively with glomerular filtration rate as well as or better than that of serum creatinine, suggesting a constant formation, and elimination from extracellular fluid mainly by glomerular filtration. It is not known, however, how well the renal plasma clearance of this 13-kDa basic polypeptide matches the glomerular filtration rate. This was investigated in rats during control conditions and after reduced renal perfusion pressure. 125I-cystatin C and an indicator for glomerular filtration (51Cr-EDTA or 131I-aprotinin) were injected intravenously. The renal accumulation and urinary excretion of the tracers were recorded in periods of 2.5 to 20.0 min. The renal plasma clearance of 125I-cystatin... (More)

Serum cystatin C concentration correlates negatively with glomerular filtration rate as well as or better than that of serum creatinine, suggesting a constant formation, and elimination from extracellular fluid mainly by glomerular filtration. It is not known, however, how well the renal plasma clearance of this 13-kDa basic polypeptide matches the glomerular filtration rate. This was investigated in rats during control conditions and after reduced renal perfusion pressure. 125I-cystatin C and an indicator for glomerular filtration (51Cr-EDTA or 131I-aprotinin) were injected intravenously. The renal accumulation and urinary excretion of the tracers were recorded in periods of 2.5 to 20.0 min. The renal plasma clearance of 125I-cystatin C (Ccy) based on the renal content of 125I correlated well with the glomerular filtration rate (CCr-EDTA) in periods up to 6 min; i.e. Ccy = 0.94 x CCr-EDTA, r = 0.99. Less than 0.5% of the filtered amount appeared in the urine. During more prolonged periods, Ccy increasingly underestimated glomerular filtration rate, reaching about 0.4 x CCr-EDTA in a 20-min period. Free 125I relative to total plasma 125I activity increased from about 2% at 5 min to about 70% at 20 min. In nephrectomized rats, free 125I accumulated in plasma at a slower rate, accounting for about 15% of the total activity 20 min after injection of 125I-cystatin C. We conclude that cystatin C is (a) mainly removed from the extracellular fluid by the kidneys, (b) practically freely filtered in the glomeruli, and (c) completely absorbed and rapidly broken down by the proximal tubular cells.

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type
Contribution to journal
publication status
published
subject
keywords
Animals, Aprotinin/pharmacokinetics, Chromium Radioisotopes, Cystatin C, Cystatins/pharmacokinetics, Cysteine Proteinase Inhibitors/pharmacokinetics, Edetic Acid/pharmacokinetics, Female, Glomerular Filtration Rate, Humans, Iodine Radioisotopes, Kidney/metabolism, Rats, Rats, Sprague-Dawley
in
Scandinavian Journal of Clinical and Laboratory Investigation
volume
56
issue
5
pages
409 - 414
publisher
Informa Healthcare
external identifiers
  • scopus:0029789543
  • pmid:8869663
ISSN
0036-5513
DOI
10.3109/00365519609088795
language
English
LU publication?
yes
id
e95eb2ad-6196-46f8-87d1-3aa5348da7f3
date added to LUP
2021-10-29 09:38:44
date last changed
2024-04-20 15:24:38
@article{e95eb2ad-6196-46f8-87d1-3aa5348da7f3,
  abstract     = {{<p>Serum cystatin C concentration correlates negatively with glomerular filtration rate as well as or better than that of serum creatinine, suggesting a constant formation, and elimination from extracellular fluid mainly by glomerular filtration. It is not known, however, how well the renal plasma clearance of this 13-kDa basic polypeptide matches the glomerular filtration rate. This was investigated in rats during control conditions and after reduced renal perfusion pressure. 125I-cystatin C and an indicator for glomerular filtration (51Cr-EDTA or 131I-aprotinin) were injected intravenously. The renal accumulation and urinary excretion of the tracers were recorded in periods of 2.5 to 20.0 min. The renal plasma clearance of 125I-cystatin C (Ccy) based on the renal content of 125I correlated well with the glomerular filtration rate (CCr-EDTA) in periods up to 6 min; i.e. Ccy = 0.94 x CCr-EDTA, r = 0.99. Less than 0.5% of the filtered amount appeared in the urine. During more prolonged periods, Ccy increasingly underestimated glomerular filtration rate, reaching about 0.4 x CCr-EDTA in a 20-min period. Free 125I relative to total plasma 125I activity increased from about 2% at 5 min to about 70% at 20 min. In nephrectomized rats, free 125I accumulated in plasma at a slower rate, accounting for about 15% of the total activity 20 min after injection of 125I-cystatin C. We conclude that cystatin C is (a) mainly removed from the extracellular fluid by the kidneys, (b) practically freely filtered in the glomeruli, and (c) completely absorbed and rapidly broken down by the proximal tubular cells.</p>}},
  author       = {{Tenstad, O and Roald, A B and Grubb, A and Aukland, K}},
  issn         = {{0036-5513}},
  keywords     = {{Animals; Aprotinin/pharmacokinetics; Chromium Radioisotopes; Cystatin C; Cystatins/pharmacokinetics; Cysteine Proteinase Inhibitors/pharmacokinetics; Edetic Acid/pharmacokinetics; Female; Glomerular Filtration Rate; Humans; Iodine Radioisotopes; Kidney/metabolism; Rats; Rats, Sprague-Dawley}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{409--414}},
  publisher    = {{Informa Healthcare}},
  series       = {{Scandinavian Journal of Clinical and Laboratory Investigation}},
  title        = {{Renal handling of radiolabelled human cystatin C in the rat}},
  url          = {{http://dx.doi.org/10.3109/00365519609088795}},
  doi          = {{10.3109/00365519609088795}},
  volume       = {{56}},
  year         = {{1996}},
}