The relationship between surgical outcomes and KCNJ5 mutations and pathological classification in patients with unilateral primary aldosteronism.

Objective: To investigate the correlations of KCNJ5 gene mutations and pathological subtypes based on 11β-hydroxylase (CYP11B1)/aldosterone synthase (CYP11B2) immunohistochemistry with clinical characteristics and postoperative outcomes in patients with unilateral primary aldosteronism undergoing adrenalectomy. Methods: This retrospective study enrolled 155 patients with primary aldosteronism who underwent unilateral adrenalectomy at the Department of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, between May 2023 and May 2024. KCNJ5 mutations were detected by Sanger sequencing, and patients were stratified into KCNJ5-mutant and wild-type groups based on genetic results. The KCNJ5-mutant cohort was further subclassified into complete remission and partial remission groups according to surgical outcomes. For KCNJ5-mutant cases, postoperative tissues underwent immunohistochemical subtyping for CYP11B1/CYP11B2 expression, and were divided into the CYP11B2 mono-positive group (CYP11B1-/CYP11B2+) and the CYP11B1/CYP11B2 co-expression group (CYP11B1+/CYP11B2+). Correlations of KCNJ5 mutations and pathological subtypes with baseline characteristics, biochemical profiles, and postoperative outcomes in unilateral primary aldosteronism patients were analyzed. Results: A total of 100 patients were included in the final analysis, aged (51.1±11.0) years, including 35 females (35%). The somatic KCNJ5 mutation rate was 69% (69/100), with 69 KCNJ5-mutant and 31 wild-type cases. Compared to wild-type patients, KCNJ5-mutant patients were younger ((48.4±10.8) years vs. (56.9±9.3) years, P=0.000 2), had a higher female proportion (45% vs. 13%, P=0.004 0), exhibited lower preoperative renin levels (3.4 (1.1, 39.5) ng/L vs. 9.7 (2.7, 19.6) ng/L, P=0.009 1) and had a higher rate of complete clinical remission (55% vs. 16%, P=0.000 3). Among KCNJ5-mutant patients, 38 achieved complete remission and 31 achieved partial remission. The complete remission group demonstrated younger age ((45.6±10.2) years vs. (52.0±10.5) years, P=0.012 6), shorter hypertension duration ((6.2±6.1) years vs. (10.7±10.1) years, P=0.020 4), higher preoperative plasma (951.5 (652.2, 1 690.8) pmol/L vs. 749.8 (518.5, 955.4) pmol/L, P=0.027 7) and urinary ((86 271.4±51 873.8) pmol/24 h vs. (61 860.2±24 411.2) pmol/24 h, P=0.019 2) aldosterone levels, greater lateralization index (22.6 (10.1, 42.5) vs. 11.1 (5.1, 19.8), P=0.022 7), fewer baseline antihypertensive defined daily dose (2.6±1.3 vs. 4.0±1.3, P<0.000 1), and larger tumor diameter (1.5 (1.2, 1.8) cm vs. 1.1 (1.0, 1.5) cm, P=0.000 7). Immunohistochemical subtyping revealed CYP11B2 mono-positivity in 24 mutant cases and CYP11B1/CYP11B2 co-expression in 45. The CYP11B2 mono-positive group showed more pronounced postoperative reduction in antihypertensive defined daily dose (2.9±1.3 vs. 2.2±1.2, P=0.018 3), though no significant difference in complete remission rates (46% vs. 60%, P=0.259 8) was observed. Conclusion: In patients with unilateral primary aldosteronism, those carrying KCNJ5 somatic mutations exhibit characteristics such as younger age and a higher proportion of females compared to wild-type patients, along with significantly better surgical outcomes. Moreover, among patients with KCNJ5 mutations, those whose pathological subtype shows pure CYP11B2 expression demonstrate a more pronounced reduction in postoperative antihypertensive defined daily dose than those with co-expression of CYP11B1/CYP11B2.