Determination of reference intervals for common chemistry and immunoassay tests for Kenyan adults based on an internationally harmonized protocol and up-to-date statistical methods

Abstract

Background Due to a lack of reliable reference intervals (RIs) for Kenya, we set out to determine RIs for 40 common chemistry and immunoassay tests as part of the IFCC global RI project. Methods Apparently healthy adults aged 18-65 years were recruited according to a harmonized protocol and samples analyzed using Beckman-Coulter analyzers. Value assigned serum panels were measured to standardize chemistry results. The need for partitioning reference values by sex and age was based on between-subgroup differences expressed as standard deviation ratio (SDR) or bias in lower or upper limits (LLs and ULs) of the RI. RIs were derived using a parametric method with/without latent abnormal value exclusion (LAVE). Results Sex-specific RIs were required for uric acid, creatinine, total bilirubin (TBil), total cholesterol (TC), ALT, AST, CK, GGT, transferrin, transferrin saturation (TfSat) and immunoglobulin-M. Age-specific RIs were required for glucose and triglyceride for both sexes, and for urea, magnesium, TC, HDL-cholesterol ratio, ALP, and ferritin for females. LAVE was effective in optimizing RIs for AST, ALT, GGT iron-markers and CRP by reducing influence of latent anemia and metabolic diseases. Thyroid profile RIs were derived after excluding volunteers with anti-thyroid antibodies. Kenyan RIs were comparable to those of other countries participating in the global study with a few exceptions such as higher ULs for TBil and CRP.

The indirect method in the establishment of reference intervals for complement 3 and complement 4: A retrospective study

“…Several studies have shown that the RIs established by the parametric method are narrower than those established by the nonparametric method. 22 , 29 Furthermore, different compositions and performances were found in the instruments, which led to various test results. The difference in the RIs for C3, compared with other studies, was more significant than that for C4; this phenomenon has occurred in other studies.…”

Clinical laboratory reference values in adults in Kisumu County, Western Kenya; hematology, chemistry and CD4

“…We use the critical value of SDR>0.3 to signify significant difference between sex-specific assay medians to warrant sex-specific RIs. As SDR is a measurement of different from the point of centrality, we also include a comparison metric, “Bias Ratio” (BR), which may more appropriately characterize difference between groups at the extremes of the distribution [ 30 ]. The BR calculation examines the dispersion for the RI at the extremes for male and female values compared to the extremes for the combined population divided by standard deviation (SD) comprising reference interval (i.e.…”

“…In order to depict the practical magnitude of the statistical difference between male and female RIs, we calculate the standard deviation ratio (SDR) using a 1-way ANOVA approach to determine the within-group deviation from the overall median value [28][29][30]. We use the critical value of SDR>0.3 to signify significant difference between sex-specific assay medians to warrant sex-specific RIs.…”

Cohort Profile: Swiss BioRef: The building blocks of a nationwide IT infrastructure in Switzerland for generating precise reference intervals

“…for the nomenclature, terminology, units and formats used, to ensure reproducibility of all the steps of the total laboratory testing procedure, possibly for international application[10,11]. This is an on-going global process, as laboratories in Europe[12–17], Africa[18–20], North America[21], Asia[22–24] and Australia[25] aim to derive nation-specific RIs with multicentre studies.…”