Urinary cystatin C as a specific marker of tubular dysfunction.
BACKGROUND
Cystatin C (CST3), a strong inhibitor of cysteine proteinases, is freely filtered by the kidney glomerulus and is reabsorbed by the tubules, where it is almost totally catabolized, with the remainder then eliminated in urine. In tubular diseases, it seems sensible to postulate that CST3 degradation would be reduced and consequently an increase in its urinary elimination would be observed.


METHODS
We report here the development of an automatic quantitative assay to measure CST3 concentrations in urine using a Behring N-Latex Cystatin C kit on a BNII laser nephelometer. We tested its clinical relevance on several kidney disease patients.


RESULTS
This assay is sensitive (limit of detection 0.008 mg/L) and precise (within- and between-day CVs < 4%). Reference values for freshly collected urine samples range from 0.03 to 0.18 mg/L. Mean urine CST3 concentrations obtained from 52 patients with kidney tubular disease (4.31 +/- 3.85 mg/L) were significantly higher than those for 60 controls (0.096 +/- 0.044 mg/L; p < 0.0001) and 47 glomerular disease patients (0.106 +/- 0.133 mg/L; p < 0.0001).


CONCLUSIONS
Increased urinary CST3 concentrations allow the accurate detection of tubular dysfunction among pure and mixed nephropathies. Because of its ability to be processed on automated clinical chemistry analyzers, this assay could easily be used as an adjunct to the standard panel used to screen kidney pathologies, even in emergency situations.
Conti
Marc
M
Biochemistry Laboratory, AP-HP Bicêtre University Hospital, Le Kremlin-Bicêtre, France.
Moutereau
Stéphane
S
Zater
Mokhtar
M
Lallali
Karim
K
Durrbach
Antoine
A
Manivet
Philippe
P
Eschwège
Pascal
P
Loric
Sylvain
S
D000368:Aged; D001331:Automation; D001681:Biological Assay; D015415:Biomarkers / Q000652:urine*; D055316:Cystatin C; D015891:Cystatins / Q000652:urine*; D015853:Cysteine Proteinase Inhibitors / Q000652:urine*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000175:diagnosis / Q000652:urine; D007677:Kidney Function Tests; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D051437:Renal Insufficiency / Q000175:diagnosis / Q000652:urine*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors