Derivation of sex and age-specific reference intervals for clinical chemistry analytes in healthy Ghanaian adults

Abstract

Objectvies: This study is aimed at establishing reference intervals (RIs) of 40 chemistry and immunochemistry analytes for Ghanaian adults based on internationally harmonized protocol by IFCC Committee on Reference Intervals and Decision Limits (C-RIDL).

Methods: A total of 501 healthy volunteers aged ≥18 years were recruited from the northern and southern regions of Ghana. Blood samples were analyzed with Beckman-Coulter AU480 and Centaur-XP/Siemen auto-analyzers. Sources of variations of reference values (RVs) were evaluated by multiple regression analysis (MRA). The need for partitioning RVs by sex and age was guided by the SD ratio (SDR). The RI for each analyte was derived using parametric method with application of the latent abnormal values exclusion (LAVE) method.

Results: Using SDR≥0.4 as threshold, RVs were partitioned by sex for most enzymes, creatinine, uric acid (UA), bilirubin, immunoglobulin-M. MRA revealed age and body mass index (BMI) as major source of variations of many analytes. LAVE lowered the upper limits of RIs for alanine/aspartate aminotransferase, γ-glutamyl transaminase and lipids. Exclusion of individuals with BMI≥30 further lowered the RIs for lipids and CRP. After standardization based on value-assigned serum panel provided by C-RIDL, Ghanaian RIs were found higher for creatine kinase, amylase, and lower for albumin and urea compared to other collaborating countries.

Conclusions: The LAVE effect on many clinical chemistry RIs supports the need for the secondary exclusion for reliable derivation of RIs. The differences in Ghanaian RIs compared to other countries underscore the importance of country specific-RIs for improved clinical decision making.

Keywords: AG, anion gap; ALP, alkaline phosphatase; ALT, alanine aminotransferase; AMY, amylase; AST, aspartate aminotransferase; Alb, albumin; BD, Becton Dickinson; BMI, body mass index; BR, bias ratio; C-RIDL, Committee on Reference Intervals and Decision Limits; C3, complement component 3; C4, complement component 4; CDL, clinical decision limit; CI, confidence interval; CK, creatine kinase; CRP, C-reactive protein; CV(b), CV of the regression slope b; Ca, calcium; Cl, chloride; Cre, creatinine; DBil, direct bilirubin; F, female; GGT, gamma-glutamyl transferase; Glb, globulin; Glu, glucose; HDL-CHDL-C, high-density lipoprotein cholesterol; HbA1c, hemoglobin A1c; IFCC, International Federation of Clinical Chemistry and Laboratory Medicine; IP, inorganic phosphate; IgA, immunoglobulin A; IgG, immunoglobulin G; IgM, immunoglobulin M; K, potassium; LAVE, latent abnormal values exclusion; LDH, lactate dehydrogenase; LDL-C, low-density lipoprotein cholesterol; LL, lower limit; M, male; MF, male + female; MRA, multiple regression analysis; Mg, magnesium; NP, non-parametric; Na, sodium; P, parametric; RI, reference interval; RV, reference values; SDR, standard deviation ratio; SV, sources of variation; TBil, total bilirubin; TC, total cholesterol; TCO2, total carbon dioxide; TG, triglycerides; TP, total protein; UA, uric acid; UL, upper limit; between-country differences; bias ratio; eGFR, estimated glomerular filtration rate; ethnicity; latent abnormal values exclusion method; multiple regression analysis; nonparametric method; parametric method; rp, standardized partial correlation coefficient; standard deviation ratio; standardization.