title: The cystatin C/creatinine ratio, a marker of glomerular filtration quality: associated factors, reference intervals, and prediction of morbidity and mortality in healthy seniors.
abstract: The ratio of cystatin C (cysC) to creatinine (crea) is regarded as a marker of glomerular filtration quality associated with cardiovascular morbidities. We sought to determine reference intervals for serum cysC-crea ratio in seniors. Furthermore, we sought to determine whether other low-molecular weight molecules exhibit a similar behavior in individuals with altered glomerular filtration quality. Finally, we investigated associations with adverse outcomes. A total of 1382 subjectively healthy Swiss volunteers aged 60 years or older were enrolled in the study. Reference intervals were calculated according to Clinical & Laboratory Standards Institute (CLSI) guideline EP28-A3c. After a baseline exam, a 4-year follow-up survey recorded information about overall morbidity and mortality. The cysC-crea ratio (mean 0.0124 ± 0.0026 mg/μmol) was significantly higher in women and increased progressively with age. Other associated factors were hemoglobin A1c, mean arterial pressure, and C-reactive protein (P < 0.05 for all). Participants exhibiting shrunken pore syndrome had significantly higher ratios of 3.5-66.5 kDa molecules (brain natriuretic peptide, parathyroid hormone, β2-microglobulin, cystatin C, retinol-binding protein, thyroid-stimulating hormone, α1-acid glycoprotein, lipase, amylase, prealbumin, and albumin) and creatinine. There was no such difference in the ratios of very low-molecular weight molecules (urea, uric acid) to creatinine or in the ratios of molecules larger than 66.5 kDa (transferrin, haptoglobin) to creatinine. The cysC-crea ratio was significantly predictive of mortality and subjective overall morbidity at follow-up in logistic regression models adjusting for several factors. The cysC-crea ratio exhibits age- and sex-specific reference intervals in seniors. In conclusion, the cysC-crea ratio may indicate the relative retention of biologically active low-molecular weight compounds and can independently predict the risk for overall mortality and morbidity in the elderly.
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Schaan, Liechtenstein; Tallinn University of Technology, Faculty of Science, Tallinn, Estonia.
authors.forename: Mette-Triin
authors.initials: MT
authors.lastname: Purde
authors.affiliation: Private University, Triesen, Liechtenstein.
authors.forename: Stefan
authors.initials: S
authors.lastname: Nock
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Schaan, Liechtenstein; Division of Clinical Biochemistry, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Risch
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Liebefeld, Switzerland.
authors.forename: Pedro
authors.initials: P
authors.lastname: Medina Escobar
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Liebefeld, Switzerland.
authors.forename: Chris
authors.initials: C
authors.lastname: Grebhardt
authors.affiliation: Labormedizinisches Zentrum Dr. Risch, Liebefeld, Switzerland.
authors.forename: Urs E
authors.initials: UE
authors.lastname: Nydegger
authors.affiliation: Department of Endocrinology, Diabetes and Clinical Nutrition, Bern University Hospital, and University of Bern, Bern, Switzerland.
authors.forename: Zeno
authors.initials: Z
authors.lastname: Stanga
authors.affiliation: Kantonsspital Graubünden, Zentrallabor, Chur, Switzerland. Electronic address: martin.risch@ksgr.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Risch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D003404:Creatinine / Q000097:blood*; D055316:Cystatin C / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D009017:Morbidity; D009026:Mortality; D012016:Reference Values
chemical_list: D015415:Biomarkers; D055316:Cystatin C; D003404:Creatinine