Verification of sex- and age-specific reference intervals for 13 serum steroids determined by mass spectrometry: evaluation of an indirect statistical approach.

OBJECTIVES: Conventionally, reference intervals are established by direct methods, which require a well-characterized, obviously healthy study population. This elaborate approach is time consuming, costly and has rarely been applied to steroid hormones measured by mass spectrometry. In this feasibility study, we investigate whether indirect methods based on routine laboratory results can be used to verify reference intervals from external sources. METHODS: A total of 11,259 serum samples were used to quantify 13 steroid hormones by mass spectrometry. For indirect estimation of reference intervals, we applied a "modified Hoffmann approach", and verified the results with a more sophisticated statistical method (refineR). We compared our results with those of four recent studies using direct approaches. RESULTS: We evaluated a total of 81 sex- and age-specific reference intervals, for which at least 120 measurements were available. The overall agreement between indirectly and directly determined reference intervals was surprisingly good as nearly every fourth reference limit could be confirmed by narrow tolerance limits. Furthermore, lower reference limits could be provided for some low concentrated hormones by the indirect method. In cases of substantial deviations, our results matched the underlying data better than reference intervals from external studies. CONCLUSIONS: Our study shows for the first time that indirect methods are a valuable tool to verify existing reference intervals for steroid hormones. A simple "modified Hoffmann approach" based on the general assumption of a normal or lognormal distribution model is sufficient for screening purposes, while the refineR algorithm may be used for a more detailed analysis.

CKD prevalence based on real-world data: continuous age-dependent lower reference limits of eGFR with CKD-EPI, FAS and EKFC algorithms.

PURPOSE: Several recent articles discuss the need for a definition of chronic kidney disease (CKD) that embarks age-dependency and its impact on the prevalence of CKD. The relevance is derived from the common knowledge that renal function declines with age. The aim of this study was to calculate age-dependent eGFR lower reference limits and to consider their impact on the prevalence of CKD. METHODS: A real-world data set from patients with inconspicuous urinalysis was used to establish two quantile regression models which were used to calculate continuous age-dependent lower reference limits of CKD-EPI, FAS and EKFC-eGFR based on either single eGFR determinations or eGFR values that are stable over a period of at least 3 months (± 10% eGFR). The derived lower reference limits were used to calculate the prevalence of CKD in a validation data set. Prevalence calculation was done once without and once with application of the chronicity criterion. RESULTS: Both models yielded age-dependent lower reference limits of eGFR that are comparable to previously published data. The model using patients with stable eGFR resulted in higher eGFR reference limits. By applying the chronicity criterion, a lower prevalence of CKD was calculated when compared to one-time eGFR measurements (CKD-EPI: 9.8% vs. 8.3%, FAS: 8.0% vs. 7.2%, EKFC: 9.0% vs. 7.1%). CONCLUSION: The application of age-dependent lower reference intervals of eGFR together with the chronicity criterion result in a lower prevalence of CKD which supports the estimates of recently published work and the idea of introducing age-dependency into the definition of CKD.

Estimated Prevalence of Harmful Alcohol Consumption in Pregnant and Nonpregnant Women in Saxony-Anhalt (NorthEast Germany) Using Biomarkers.

BACKGROUND: Alcohol consumption is commonly accepted in Western societies and is a known risk factor in pregnancy, which could lead to fetal alcohol spectrum disorders (FASDs). Prevalence of alcohol consumption during pregnancy is mostly unknown. Prevalence estimates in publications based on questionnaires are limited by possible underreporting due to social stigmatization. The aim of this study was to estimate the prevalence of harmful alcohol consumption in a large cohort of pregnant women using different biomarkers related to alcohol consumption and compare the findings with those of non-pregnant women METHODS: Routine parameters known to be influenced by alcohol consumption (γ-glutamyltransferase, GGT; carbohydrate-deficient transferrin, CDT/%CDT; mean corpuscular/cell volume, MCV; combined parameter of GGT and %CDT, GGT-CDT) were analyzed in serum samples of 2,182 pregnant women and 743 non-pregnant, age-matched females. Data were tested for (i) differences between pregnant and non-pregnant women and (ii) changes across the 3 trimesters of pregnancy. RESULTS: Prevalence rates differ greatly according to the parameter and cutoff, which reflects the limitations of assessing alcohol consumption with biomarkers. The prevalence of harmful alcohol consumption on the basis of a single or several elevated parameters was 13.8% (95% CI: 12.4 to 15.2) in pregnant women and 18.6% (95% CI: 15.8 to 21.4) in non-pregnant women, though 85.0% of the elevated measurements were attributable to an isolated elevation in %CDT only. Using GGT-CDT as the parameter with the highest specificity according to the literature, the estimated prevalence of harmful alcohol consumption in pregnancy is 0.5% (95% CI: 0.2 to 0.7). CONCLUSION: Estimated prevalence rates differ greatly with respect to the biomarkers and cutoffs used. The use of CDT/%CDT alone appears to overestimate harmful alcohol consumption during pregnancy.