Current criteria for the diagnosis of CKD in adults include persistent signs of kidney damage, such as increased urine albumin-to-creatinine ratio or a GFR below the threshold of 60 ml/min per 1.73 m². This threshold has important caveats because it does not separate kidney disease from kidney aging, and therefore does not hold for all ages. In an extensive review of the literature, we found that GFR declines with healthy aging without any overt signs of compensation (such as elevated single-nephron GFR) or kidney damage. Older living kidney donors, who are carefully selected based on good health, have a lower predonation GFR compared with younger donors. Furthermore, the results from the large meta-analyses conducted by the CKD Prognosis Consortium and from numerous other studies indicate that the GFR threshold above which the risk of mortality is increased is not consistent across all ages. Among younger persons, mortality is increased at GFR <75 ml/min per 1.73 m², whereas in elderly people it is increased at levels <45 ml/min per 1.73 m². Therefore, we suggest that amending the CKD definition to include age-specific thresholds for GFR. The implications of an updated definition are far reaching. Having fewer healthy elderly individuals diagnosed with CKD could help reduce inappropriate care and its associated adverse effects. Global prevalence estimates for CKD would be substantially reduced. Also, using an age-specific threshold for younger persons might lead to earlier identification of CKD onset for such individuals, at a point when progressive kidney damage may still be preventable.

BACKGROUND: Many different cystatin C–based equations exist for estimating glomerular filtration rate. Major reasons for this are the previous lack of an international cystatin C calibrator and the nonequivalence of results from different cystatin C assays. METHODS: Use of the recently introduced certified reference material, ERM-DA471/IFCC, and further work to achieve high agreement and equivalence of 7 commercially available cystatin C assays allowed a substantial decrease of the CV of the assays, as defined by their performance in an external quality assessment for clinical laboratory investigations. By use of 2 of these assays and a population of 4690 subjects, with large subpopulations of children and Asian and Caucasian adults, with their GFR determined by either renal or plasma inulin clearance or plasma iohexol clearance, we attempted to produce a virtually assay-independent simple cystatin C–based equation for estimation of GFR. RESULTS: We developed a simple cystatin C–based equation for estimation of GFR comprising only 2 variables, cystatin C concentration and age. No terms for race and sex are required for optimal diagnostic performance. The equation, $$\text{eGFR}=130\times \text{cystatin}\hspace{0.17em}{\mathrm{C}}^{-1.069}\times {\text{age}}^{-0.117}-7,$$ is also biologically oriented, with 1 term for the theoretical renal clearance of small molecules and 1 constant for extrarenal clearance of cystatin C. CONCLUSIONS: A virtually assay-independent simple cystatin C–based and biologically oriented equation for estimation of GFR, without terms for sex and race, was produced.

The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmö equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately. The study included 3495 examinations in 2847 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 52 mL/min/1.73 m²). Bias, precision [interquartile range (IQR)] and accuracy [percentage of estimates ±10% (P₁₀) and ±30% (P₃₀) of mGFR] were compared. The overall results of LM Revised/MDRD/CKD-EPI were: median bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m², P₁₀ 40%/35%/35% and P₃₀ 84%/75%/76%. LM Revised was the most stable equation in terms of bias, precision and accuracy across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI overestimated mGFR in patients with decreased kidney function, young adults and elderly. All three equations overestimated mGFR and had low accuracy in patients with BMI <20 kg/m², most pronounced among men. In settings similar to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due to its higher accuracy and more stable performance across GFR, age and BMI intervals.

This paper, prepared by the EFLM Task and Finish Group on Allocation of laboratory tests to different models for performance specifications (TFG-DM), is dealing with criteria for allocating measurands to the different models for analytical performance specifications (APS) recognized in the 1st EFLM Strategic Conference Consensus Statement. Model 1, based on the effect of APS on clinical outcome, is the model of choice for measurands that have a central role in the decision-making of a specific disease or clinical situation and where cut-off/decision limits are established for either diagnosing, screening or monitoring. Total cholesterol, glucose, HbA_1c, serum albumin and cardiac troponins represent practical examples. Model 2 is based on components of biological variation and should be applied to measurands that do not have a central role in a specific disease or clinical situation, but where the concentration of the measurand is in a steady state. This is best achieved for measurands under strict homeostatic control in order to preserve their concentrations in the body fluid of interest, but it can also be applied to other measurands that are in a steady state in biological fluids. In this case, it is expected that the “noise” produced by the measurement procedure will not significantly alter the signal provided by the concentration of the measurand. This model especially applies to electrolytes and minerals in blood plasma (sodium, potassium, chloride, bicarbonate, calcium, magnesium, inorganic phosphate) and to creatinine, cystatin C, uric acid and total protein in plasma. Model 3, based on state-of-the-art of the measurement, should be used for all the measurands that cannot be included in models 1 or 2.

Scientists of disciplines in clinical laboratory sciences have long worked on a common language for efficient and safe request of investigations, report of results, and communication of experience and scientific achievements. Widening the scope, most scientific disciplines, not only clinical laboratory sciences, rely to some extent on various examinations in addition to measurements. The ‘International vocabulary of metrology – Basic and general concepts and associated terms’ (VIM), is designed for metrology, the science of measurement. The aim of this vocabulary is to suggest definitions and explanations of concepts and a selection of terms related to nominal properties, i.e. properties that have no size.

Eight haematological quantities were measured in EDTA anticoagulated venous blood specimens collected from 1826 healthy male and female individuals between 18 and 90 years of age in the Nordic countries (Denmark, Finland, Iceland, Norway and Sweden). The samples, collected between November 1999 and November 2001 as part of the Nordic Reference Interval Project (NORIP), were analysed on 12 different types of modern automated haematology instruments currently in use among the 60 laboratories participating in the study. Non-parametric reference intervals (between 2.5 and 97.5 percentiles) have been calculated for B-Haemoglobin (females 117-153 g/L, males 134-170 g/L), B-Erythrocytes (females 3.94-5.16 x 10(12)/L, males 4.25-5.71 x 10(12)/L), B-EVF (females 0.348-0.459, males 0.395-0.500), B-MCV (82-98 fL), Erc-MCH (27.1-33.3 pg), Erc-MCHC (317-357 g/L), B-Trc (females 165-387 x 10(9)/L, males 145 x 348 x 10(9)/L) and B-Lkc (3.5-8.8 x 10(9)/L). Partitioning of data according to age and gender was done according to a standardized procedure. For most variables the calculated reference intervals corresponded well with older and less well-defined reference intervals. The mean concentration of B-Haemoglobin increased by 0.08 g/L per year of age in women, and decreased by 0.1 g/L per year of age in men. B-Haemoglobin increased with body mass index in both men and women. Smoking increased the mean of B-Lkc by 1.1 x 10(9)/L and regular use of alcohol increased the mean of B-MCV by 0.8 fL. The influence of these factors was small overall and did not promote specific reference intervals.