Albertine Donker

Chapter 7 238 Biochemical correlates of serum hepcidin concentrations We performed also regression analyses adjusted for age and sampling time because of the demonstrated correlation with age and the earlier described circadian rhythm of serum hepcidin levels. 20,40 In these adjusted analyses, ferritin was most strongly associated with serum hepcidin concentration (ß= 1.31; 95 % CI 0.95–1.68 and ß= 0.92; 95% CI 0.47–1.77 for males and females respectively) and was responsible for the largest amount of explained variance (adjusted R 2 38.8 % and 19.9 %, R 2 for age and sampling time alone 18.9 % and 7.8 % in males and females respectively)( Table 3 ). These results indicate that a 1% change in serum ferritin in micrograms per liter was associated with a 1.31% and 0.92% change in serum hepcidin concentration (nmol/l) in males and females respectively. We observed a negative association between Total Iron Binding Capacity (TIBC) and serum hepcidin concentration for both sexes. CRP demonstrated a positive association with serum hepcidin in both males and females. A sex-specific multivariable regression model was constructed including age as a dichotomous variable (<12 years vs > 12 years), time of blood sampling and those variables that were significantly ( p < 0.1) associated with serumhepcidin concentrations after adjustment for age and time of blood sampling. For males these were ferritin, TIBC, ALT, CRP and BMI; for females these were ferritin, TIBC and CRP. In males, independent correlates (p<0.1) were age, sampling time, ferritin, underweight BMI and CRP; in females age, sampling time > 3 PM, ferritin. In males, the model explained 40.9 % of the serum hepcidin variation, in females 16.9% ( Table 4 ). Age- and sex-specific reference ranges for hepcidin/ferritin and TSAT/hepcidin ratios Reference ranges (p.25- p75), minimum and maximum values of hepcidin/ferritin and TSAT/hepcidin ratios are given per age group and sex in Table 2 . We chose the TSAT/hepcidin ratio instead of other earlier reported variants, e.g. TSAT/(log)hepcidin ratio 6 since this ratio was superior in discriminating IRIDA patients from IDA non-IRIDA patients in a study we recently performed in adults in our institution (unpublished results, Netherlands Trial Register, Trial NL 6845). 41