Renal handling of radiolabelled human cystatin C in the rat
(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.
(Less)
- author
- Tenstad, O ; Roald, A B ; Grubb, A LU and Aukland, K
- organization
- publishing date
- 1996
- 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
-
- pmid:8869663
- scopus:0029789543
- 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
- 2024-06-29 21:23:19
@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}}, }