[Show abstract][Hide abstract] ABSTRACT: Abstract Background: In chronic kidney diseases of various etiologies, the urinary excretion of uromodulin is usually decreased in parallel with the glomerular filtration rate. This study aimed to investigate whether serum uromodulin is associated with kidney function. Methods: Within the framework of the Seniorlabor study, a subset of subjectively healthy individuals 60 years of age and older were included in the study. Serum uromodulin was measured with ELISA. The relationship between serum uromodulin and different stages of kidney function (i.e., cystatin C-based 2012-CKD-EPI eGFRCysC>90 mL/min/1.73 m2, 60-89 mL/min/1.73 m2, 45-59 mL/min/1.73 m2, and <45 mL/min/1.73 m2) was investigated. Furthermore, the relationship between serum uromodulin and other markers of kidney function (i.e., creatinine, cystatin C, and urea) was assessed. Results: In total, 289 participants (140 males/149 females; mean age 71±7 years) were included in the study. There were significant differences in serum uromodulin among the four groups according to different kidney function stages (p<0.001). Serum uromodulin displayed inverse relationships with creatinine (r=-0.39), cystatin C (r=-0.42), and urea (r=-0.30) and, correspondingly, a positive relationship with eGFRCysC (r=0.38, p<0.001 for all). These associations remained intact when fitting a regression model that incorporated age, gender, body mass index, and current smoking status as covariates. Conclusions: Serum uromodulin behaves in a manner opposite that of the different conventional renal retention markers by displaying lower concentrations with decreasing kidney function. As uromodulin is produced by the cells of the thick ascending limb of the loop of Henle, lower uromodulin serum levels may reflect a reduction in number or function of these cells in chronic kidney disease.
Clinical chemistry and laboratory medicine : CCLM / FESCC. 06/2014;
[Show abstract][Hide abstract] ABSTRACT: Vitamin D and the components of humoral immunity play important roles in human health. Older people have lower 25-hydroxyvitamin D (25(OH)D) serum levels than younger adults. We aimed to determine the levels of 25(OH)D serum concentrations in healthy senior citizens and to study their relationship to the levels of components of humoral immunity.
A total of 1,470 healthy Swiss men and women, 60 years or older, were recruited for this study. A total of 179 subjects dropped out of the study because of elevated serum concentrations of C-reactive protein. Fasting blood sera were analyzed for 25(OH)D with the high-performance liquid chromatography (HPLC) and for parathyroid hormone (PTH), immunoglobulins and complement C4 and C3 concentrations with immunoassays. The percentage of participants in each of the four 25(OH)D deficiency groups - severely deficient (<10 ng/ml), deficient (10 to 20), insufficient (21 to 30 ng/ml) and normal (>31 ng/ml) - were statistically compared. The relationship of the major components of the humoral system and age with 25(OH)D levels was also assessed.
About 66% of the subjects had insufficient levels of 25(OH)D. Normal levels of 25(OH)D were found in 26.1% of the subjects of which 21% were males and 30.5% were females (total study population). Severely deficient levels of 25(OH)D were found in 7.98% of the total study population. Low levels of 25(OH)D were positively associated with IgG2 (P < 0.01) and with C4 (P < 0.02), yet were inversely related to levels of IgG1 and IgA (P < 0.05) and C3 (P < 0.01). Serum levels of total IgA, IgG, IgG2 and IgG4 peaked together with 25(OH)D during late summer.
Approximately two-thirds of the healthy, older Swiss population presented with Vitamin D insufficiency. The incremental shift in IgA and C3 levels might not necessarily reflect a deranged humoral immune defense; however, given the high prevalence of vitamin D deficiency, the importance of this condition in humoral immunity will be worth looking at more closely. This study supports the role of vitamin D in the competent immune system.
BMC Medicine 08/2013; 11(1):176. · 6.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: “Senior Labor” Study: a New Definition of Normal Hemoglobin Values in Elderly Healthy Individuals
Lorenz Risch1,2, Corina Risch2, Pedro Medina1, Urs E. Nydegger1, Martin Risch4,
and Jean-François Lambert3.
1 Labormedizinisches Zentrum Dr. Risch, Liebefeld, Switzerland
2 University of Triesen, Liechtenstein
3 University hospital of Lausanne, Switzerland
4 Kantonsspital Chur, Switzerland
With increasing mean age of the world population it becomes clear that biological and chronological ages might diverge on individual levels. In contrast to working age adults, elderly people have a higher incidence of anemia mostly in association with medical comorbidities (Artz, Fergusson et al. 2004, Merchant and Roy 2012). Incidence of anemia in the elderly has so far been investigated in large studies mostly performed on hospitalized patients, nursing homes subjects or mobile examination centers subjects seeking medical care with a variety of complaints (Kikuchi, Inagaki et al. 2001, Guralnik, Eisenstaedt et al. 2004). In the USA, the 3rd NHANES study focused on racial groups of elderly revealing a prevalence of anemia in men and women >65 yrs of ~10% (Izaks, Westendorp et al. 1999, Guralnik, Ershler et al. 2005). In patients over 85 yrs, this number exceeded 20%.
Current reference intervals for clinical laboratory assays are based on younger adult’s samples. Physiologic concentrations of hemoglobin (Hb) in human blood range from 120 g/l (female) and 130 g/l (male) to 168 g/l (both genders) under which anemia and above which polycythemia get diagnosed. We are currently in need for reference ranges suited for normal older subject and unbiased by already debilitated individuals. The defining cut-offs provided by the WHO are 120 g/l for women and 130 g/l for men (WHO Technical Report Series 1968); although older age is generally associated with lower Hb levels, these cut-offs do not account for age.
We have performed a large recruitment as part of our “Senior Labor” study (Risch, Medina et al. 2012). In contrast to previous studies, we have prospectively recruited healthy Caucasian elderly over 60, implementing strong exclusion criteria for participating subjects. For those “healthy individuals, a complete blood count (CBC) as well as frequently performed clinical laboratory tests were prospectively performed.
A total of 1255 subjects consented to enrol for the study after having passed the primary clinical exclusion criteria which comprised one or more of the following questions affirmatively answered (primary exclusion criteria): drugs: do you take drugs containing steroids, are you under ill-adjusted antihypertensive therapy, do you suffer from thyroid diseases/are you substituted with thyroid hormones, do you have diabetes mellitus, have you suffered from cancer during the last 5 years, were you hospitalized during the month prior to enrolment and do you abuse alcohol.
Complete blood count assays were done using an XE-5000 hematology analyzer and clinical chemistry assays followed routine workflow on modular platforms.
We evaluated 696 women and 559 with ages ranging from 60 to 99 years old. Mean Hb and 95% confidence intervals were calculated using logarithmic transformation in order to correct of skewness of the data. Overall, women had a mean Hb of 136 (95%CI 120-155) and men had a mean Hb of 148 (95%CI 128-172). Detailed results by age groups are presented in figure 1. Hb level was steady over age groups until 74 yo for men and 80 for women. Interestingly, only a few subjects fell outside the WHO limits with 20 women having a Hb less than 120 (2.9%) and 20 men a Hb less than 130 (3.6%).
We looked for frequent causes for anemia such as low ferritin and vitamin deficiencies (folic acid and B12). In the cohort, 37 subjects had a ferritin lower than 20 µg/l (2.9%). Among these, 9/37 (24.3%) had a low Hb (WHO definition) and only one in 37 (2.7%) had a MCHC below 310.
The micronutrients folic acid and vitamin B12 were also assessed; 98 subjects (7.8%) had folic acid < 10 nmol/l. Among these individuals, 6/98 (6.1%) were anemic. The definition of vitamin B12 deficiency varies but is usually accepted as lower than 200 pmol/l in elderly persons: in the whole population, 398/1255 (31.7%) subjects had vitamin B12 levels < 200 pmol/L and 105/1255 (8.4%) had vitamin B12 concentrations less than 150 pmol/L. Using these two limits, these subjects were anemic in 11/398 (2.8%) and 4/105 (3.8%) respectively. This indicates a limited impact of folic acid and B12 deficiency on anemia of the elderly.
In this study, we were able to define new Hb reference range in elderly subjects reporting healthy by strict clinical criteria in a large cohort of subjects. Our results show a very limited proportion of subject with WHO defined anemia, thus indicating that even in older subjects, the discovery of a low Hb is likely to be associated to an underlying pathology.
Age group N Mean Hb 95% CI Hb<120
(N) N Mean Hb 95% CI Hb<130
60-64 137 136 119 - 156 3 113 151 134 - 170 1
65-69 168 138 122 - 155 1 139 150 131 - 171 3
70-74 147 137 121 - 154 4 124 150 131 - 172 3
75-79 116 136 119 - 155 5 85 147 129 - 168 2
Over 80 128 135 116 - 156 7 98 143 120 - 171 15
Overall 696 136 120 - 155 20 559 148 128 - 172 24
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis of elevated blood pressure and other cardiovascular risk factors in the population and their progression over time is still incompletely understood, especially in young and healthy adults.
The genetic and phenotypic determinants of blood pressure and other cardiovascular risk factors (GAPP) study is a population-based prospective cohort study involving a representative sample of healthy adults aged 25-41 years in the Principality of Liechtenstein. Exclusion criteria are any cardiovascular disease, diabetes, obstructive sleep apnoea syndrome, daily intake of nonsteroidal anti-inflammatory drugs and a body mass index >35 kg/m². Examinations include detailed assessment of personal, medical, lifestyle and nutritional factors, standardised assessment of weight, height and waist circumference, blood pressure measurement (clinic and 24-hour ambulatory monitoring), electrocardiography (12-lead and 24-hour Holter monitoring), bioimpedance analysis, blood, urinary and genetic sampling, spirometry and sleep pulse oximetry with nasal flow measurement. Baseline examination is still ongoing. Follow-up examinations are scheduled every 3-5 years.
Since June 2010, 1,333 participants have been enrolled. Mean age of the participants was 36.7 ± 4.9 years and 47.5% of all participants were male. Mean body mass index was 26.1 ± 3.1 kg/m2 in men and 23.5 ± 3.9 kg/m2 in women. The prevalence of hypertension and prediabetes was 24.7% and 32.1% in men and 6% and 23% in women respectively. Mean LDL levels were 3.34 ± 0.9 mmol/l in men and 2.75 ± 0.7 mmol/l in women. Median hsCRP was 0.9 (0.5; 1.8) mg/l with no gender differences.
GAPP affords an excellent opportunity to assess genetic and phenotypic predictors of cardiovascular risk factors and their progression over time in young and healthy adults from the general population.
[Show abstract][Hide abstract] ABSTRACT: β2-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 β2-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.
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 β2-microglobulin. As a marker of kidney function, the Berlin Initiative Study equation 2 for the estimation of the estimated glomerular filtration rate (eGFRBIS2) in the elderly was employed.
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 (eGFRBIS2) revealed age, male gender, and C-reactive protein level to be positively associated with β2-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.
Serum β2-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.
PLoS ONE 01/2013; 8(8):e72073. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: Data about vitamin B12 (B12) deficiency in the general population are scarce. The present study was performed to determine the prevalence of B12 deficiency in the general population of the Principality of Liechtenstein, as well as to identify sub-populations potentially at high risk. DESIGN: Retrospective study. SETTING: Ambulatory setting, population of the Principality of Liechtenstein. SUBJECTS: Seven thousand four hundred and twenty-four patients seeking medical attention whose serum samples were referred for routine work-up in an ambulatory setting were consecutively enrolled. Serum total B12 was determined in all patients in this cohort. In addition, for a subgroup of 1328 patients, serum holotranscobalamin was also measured. Prevalence of B12 deficiency was calculated. Further, multivariate logistical regression models were applied to identify covariates independently associated with B12 deficiency and depletion. RESULTS: Nearly 8 % of the general population was suffering from either B12 depletion or deficiency. The ratio between B12 depletion and deficiency was 2:1 for all age ranges. Pathological changes were detected predominantly in older people. Female gender was a significant predictor of B12 depletion. In the cohort, nearly 40 % exhibited either depletion or deficiency of B12. CONCLUSIONS: B12 depletion and deficiency are common in Liechtenstein, a Central European country. The measurement of biochemical markers represents a cost-efficient and valid assessment of the B12 state. When a deficiency of B12 is diagnosed at an early stage, many cases can be treated or prevented, with beneficial effects on individual outcomes and subsequent potential reductions in health-care costs.
Public Health Nutrition 12/2012; · 2.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Clinica chimica acta; international journal of clinical chemistry 04/2012; 413(7-8):733-9. · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: An author is generally regarded as an individual "who has made substantial intellectual academic contributions to a published study". However, the extent of the contribution that laboratory medicine professionals have made as authors of research papers in high-impact medical journals remains unclear.
From 1 January 2004 to 31 March 2009, 4837 original research articles appeared in the: New England Journal of Medicine, Lancet, Annals of Internal Medicine, JAMA and BMJ. Using authorship as an indicator of intellectual contribution, we analyzed articles that included laboratory medicine parameters in their titles in an observational cross-sectional study. We also extracted data regarding radiological topics that were published during the same time within the same journals.
Out of 481 articles concerning laboratory medicine topics, 380 provided information on the affiliations of the authors. At least one author from an institution within the field of laboratory medicine was listed in 212 articles (55.8%). Out of 3943 co-authors, only 756 (19.2%) were affiliated with laboratory medicine institutions. Authors from laboratory medicine institutions were listed as the first, last or corresponding authors in 99 articles (26.1%). The comparative proportions for author affiliation from 55 radiology articles were significantly higher, as 72.7% (p=0.026) of articles and 24.8% (p=0.001) of authors indicated an affiliation with a radiology institution. Radiology professionals from 72.7% of the articles were listed as either the first, last or corresponding authors (p<0.0001). The subgroup analysis revealed that laboratory medicine professionals from North America were significantly less frequently involved as co-authors than were their colleagues from Europe (p=0.04).
Laboratory medicine professionals are underrepresented as co-authors in laboratory medicine studies appearing in high-impact general medicine journals.
Clinical Chemistry and Laboratory Medicine 01/2012; 50(8):1305-8. · 3.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevalence of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection in a Swiss cohort among individuals consulting for screening or symptomatic reasons is not very well known.
Between January 2009 and January 2010, diagnostic samples referred to us to test for either CT or NG or both were simultaneously analysed for both infections. Testing was performed using the commercial m2000sp and m2000rt devices from Abbott Diagnostics involving automated DNA extraction and semi-quantitative real-time polymerase chain reaction (PCR), respectively.
A total of 9,245 individuals (8,009 female, 1,236 male) were tested. CT alone was found in 318 (3.97%) samples from female patients and NG infections were found in 5 (0.06%) of the female samples. Six (0.08%) women had both CT and NG infections. The numbers for males were 72 (5.83%) for CT alone, 18 (1.14%) for NG alone and 8 (0.65%) for coincident infections. Among women, a selective testing approach in which only the presence of CT was investigated missed six NG cases (0.07% prevalence, 54.55% of all NG-positive women) and the request to test only for NG missed two CT cases (0.02% prevalence, 0.62% of all CT-positive women). For the male samples, one NG case (0.08% prevalence, 3.85% of all NG-positive men) was missed when only CT was requested and three CT cases (0.24% prevalence, 3.75% of all CT-positive men) were overlooked when only NG testing was requested.
A sizeable number (12) of CT and NG cases is missed by physician-referred testing for only one of the two pathogens.
[Show abstract][Hide abstract] ABSTRACT: Background: Estimation of glomerular filtration rate (eGFR) is a crucial
measure, when it comes to detect and stage Chronic Kidney Disease
(CKD). Current guidelines recommend the use of IDMS-traceable
creatinine based abbreviated MDRD equation (IDMS-MDRD4) to
calculate eGFR. However, it has been shown that the MDRD equation
underestimates GFR especially in normal or mildly impaired kidney
function, and thus, novel equations, such as the CKD-EPI and the Mayo
Clinic Quadratic Equation (MCQE), have been developed to address
Aim: To determine the impact of the choice of equation on the
prevalence of stage 3-5 CKD.
Methods: A cross-sectional study was done in adult patients residing in
Liechtenstein. Patients seeking non-nephrological medical care and
from whom serum samples were referred for renal function assessment
were included. eGFR was calculated with IDMS-MDRD4, CKD-EPI and
Results: For 43% (n = 9378) of the entire population >25 years renal
function assessment was available. Mean values were 105 + 35 ml/
min/1.73 m2 for IDMS-MDRD4, 99 + 20 ml/min/1.73 m2 for MCQE, and
116 + 22 ml/min/1.73 m2 for CKD-EPI. An eGFR indicating chronic
kidney disease (CKD) stages 3–5 was found in 4.93% when using the
IDMS-MDRD4 equation and in 3.98% when using the MCQE. The
assessment with the nowadays recommended CKD-EPI equation
revealed a much lower prevalence of 1.80%. In comparison with
IDMS-MDRD4, CKD-EPI was associated with significantly less male
and female patients being classified as having stage 3-5 CKD [IDMSMDRD4:
164/4180 (3.92%) male, 287/5198 (5.52%) female; CKD-EPI:
105/4180 (2.51%) male (p = 0.0003), 64/5198 (1.23%) female
(p <0.0001)]. This effect was more pronounced in women.
Conclusions: In this population based study, employing the new and
more accurate CKD-EPI kidney function assessment leads to a
significantly lower prevalence of stage 3-5 CKD than obtained with the
MDRD estimate. Introduction of this new equation in clinical routine
prevents overdiagnosis of CKD, especially in women.
[Show abstract][Hide abstract] ABSTRACT: Data on the prevalence of decreased glomerular filtration rate in Europe are limited. Most of the available studies did not employ laboratory methods providing creatinine concentrations traceable to the reference method, i.e. isotope dilution mass spectrometry (IDMS).
We therefore conducted a cross-sectional study in the principality of Liechtenstein consecutively enrolling adult patients seeking non-nephrological medical care from whom serum samples were referred for renal function assessment. All measurements were done in one central laboratory. The estimated glomerular filtration rate (eGFR) was calculated based on the determination of IDMS-traceable creatinine by a kinetic Jaffe method (Roche Diagnostics, Switzerland) by means of the MDRD and Mayo Clinic quadratic equations. We further estimated the incidence of end stage renal disease during the next 5 years.
For 43% (n=9378) of the entire population>or=25 years renal function assessment was available. An eGFR indicating chronic kidney disease (CKD) stages 3-5 was found in 4.93% when using the MDRD equation and in 3.98 % when using the Mayo Clinic quadratic equation. The two equations had a very good agreement in classifying patients to have an eGFR consistent with CKD stages 3-5 (Cohen's kappa 0.887). Further calculations suggested that among patients aged 80 or younger, annually 42 per 100,000 are going to develop an eGFR<15 ml/min/1.73 m2 over the next 5 years.
4-5% of patients seeking non-nephrological medical advice have an eGFR consistent with CKD stages 3-5, and a considerable number of subjects is expected to develop end stage renal disease over a 5 year period. In order to obtain comparable kidney function estimates among different institutions it is not only important to use standardized methods to measure creatinine but rather to employ standardized methods to calculate a GFR estimate.