Establishment of region-, age- and sex-specific reference intervals for aldosterone and renin with sandwich chemiluminescence immunoassays.

Objectives: Accurate measurement of plasma aldosterone (ALD) and renin is important in primary aldosteronism screening and diagnosis. The high variability of ALD and renin due to salt intake, age, and sex, as well as the lack of immunoassay standardization necessitates the establishment of region-, age-, sex- and assay-specific reference intervals (RIs). This study established RIs for ALD and renin using novel sandwich chemiluminescent immunoassays.

Methods: ALD and renin were measured on a fully automated chemiluminescence platform (Maglumi X8, Snibe, China). The analytic performances were estimated following CLSI guidelines. A total of 2,281 healthy participants from Beijing, Jiangsu, Henan, Gansu and Guangdong were recruited.

Results: Total imprecision were 1.42-5.09 % for ALD and 1.07-4.11 % for renin. The maximum dilution rates were 50× and 10× for ALD and renin. Interferences of 22 and six interferents for ALD and renin were acceptable. The sandwich ALD immunoassay results highly correlated with LC-MS/MS (r=0.994). The RI of ALD was partitioned based on salt intake, with central 95 % RIs for males of 16.9-185 ng/L (46.8-513 pmol/L) in Guangdong and 26.5-242 ng/L (73.5-671 pmol/L) in other four regions. Females showed an age-dependent decline in ALD levels (RIs in Guangdong: 26.9-442 ng/L [74.6-1,226 pmol/L, 18-40 years], 32.4-326 ng/L [89.9-904 pmol/L, 41-60 years], 21.2-199 ng/L [58.8-552 pmol/L, >60 years], whereas males exhibited no significant change. Renin RIs: females: 3.43-89.2 mU/L (18-40 years), 0.92-67.1 mU/L (41-60 years), 0.66-55 mU/L (>60 years); males: 2.23-95.1 mU/L (≤60 years), 1.71-68.9 mU/L (>60 years).

Conclusions: This is the first study to establish accurate ALD and renin RIs for sandwich immunoassays. Region-, age- and sex-specific RIs were recommended, which will enhance the accuracy of clinical screening and diagnosis of primary aldosteronism.