The cystatin C/creatinine ratio, a marker of glomerular filtration quality: associated factors, reference intervals, and prediction of morbidity and mortality in healthy seniors.

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, ß2-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.

Factors other than the glomerular filtration rate that determine the serum beta-2-microglobulin level.

BACKGROUND: ß2-microglobulin has been increasingly investigated as a diagnostic marker of kidney function and a prognostic marker of adverse outcomes. To date, non-renal determinants of ß2-microglobulin levels have not been well described. Non-renal determinants are important for the interpretation and appraisal of the diagnostic and prognostic value of any endogenous kidney function marker. METHODS: This cross-sectional analysis was performed within the framework of the www.seniorlabor.ch study, which includes subjectively healthy individuals aged ≥ 60 years. Factors known or suspected to have a non-renal association with kidney function markers were investigated for a non-renal association with serum ß2-microglobulin. As a marker of kidney function, the Berlin Initiative Study equation 2 for the estimation of the estimated glomerular filtration rate (eGFR(BIS2)) in the elderly was employed. RESULTS: A total of 1302 participants (714 females and 588 males) were enrolled in the study. The use of a multivariate regression model adjusting for age, gender and kidney function (eGFR(BIS2)) revealed age, male gender, and C-reactive protein level to be positively associated with ß2-microglobulin levels. In addition, there was an inverse non-renal relationship between systolic blood pressure, total cholesterol and current smoking status. No association with markers of diabetes mellitus, body stature, nutritional risk, thyroid function or calcium and phosphate levels was observed. CONCLUSIONS: Serum ß2-microglobulin levels in elderly subjects are related to several non-renal factors. These non-renal factors are not congruent to those known from other markers (i.e. cystatin C and creatinine) and remind of classical cardiovascular risk factors.

Insights on urinary NGAL obtained in a primary care setting.

BACKGROUND: A majority of patients developing acute kidney injury (AKI) receive medical care from their primary care physicians prior to the occurrence of conditions that predispose them to this complication. METHODS: To characterize the uNGAL concentrations in primary care patients and to assess these concentrations with regard to different reference intervals, we conducted a multicenter, cross-sectional study with random selection of general practitioners (GP) from all GP offices in seven Swiss cantons. 1000 adults (566 females; mean age 57±17 years) were included. RESULTS: The median absolute uNGAL was 21 ng/L. Elevated uNGAL (>100 ng/L) together with normal kidney test results (eGFR and albuminuria) were found in 6.5% of all patients. Females had a significantly higher uNGAL than did males. Among a multitude of different clinical and laboratory variables, only age, gender, liver function parameters, WBC and CRP were significantly associated with uNGAL levels in a multivariate analysis. When examining the proposed KDIGO classification of chronic kidney disease, the uNGAL levels at the given eGFR stages changed with increasing albuminuria stages and vice versa. CONCLUSIONS: Age, gender, markers of inflammation and liver function, exert influences on uNGAL concentrations. A substantial proportion of patients exhibited normal kidney testing together with elevated uNGAL, potentially identifying patients with increased renal stress and at increased risk for the development of AKI.