A Meta-Analysis of Somatic KCNJ5 K+ Channel Mutations In 1636 Patients With an Aldosterone-Producing Adenoma

Context: Due to selection biases and inadequate statistical power, individual studies may fail to identify the clinical features of patients with an aldosterone-producing adenoma (APA) harboring KCNJ5 mutations. When this failure occurs, meta-analysis can provide significant outcome data. Objective: The objective was to determine the clinical features of these APA patients. Design: We systematically searched the PubMed, Scopus, Web of Science, and Cochrane databases library in January 2015 applying the Population, Intervention, Comparison, and Outcome (PICO) strategy. The standardized differences in mean and corresponding 95% confidence interval of continuous variables were computed by random-effects modeling. Setting: We performed a meta-analysis of all available studies on somatic KCNJ5 mutations in APA. Patients: We could identify 13 studies that recruited 1636 patients (age 49 +/- 4 years; 55% females). Main Outcomes and Measures: Differences between APA with and without KCNJ5 mutations in gender, plasma renin activity, plasma aldosterone, tumor size, serum potassium, and blood pressure were investigated. Results: The overall prevalence of KCNJ5 mutations was 43% (range +/- 12-80%). Their rate was lower (P < .003) in the studies done in Europe, the United States, and Australia (35%) than in Japan and China (63%); it correlated (r = 0.60, P < .029) with the mean daily urinary sodium excretion. Compared with the wild-type, the mutated APA patients were younger (45 +/- 3 vs 52 +/- 5 yrs), had higher plasma aldosterone (42 +/- 8 vs 33 +/- 8 ng/dl), larger tumors (16.1 +/- 6.4 versus 14.9 +/- 7.4 mm), and were more often females (67% vs 44%) (all P < .05). Conclusions: Meta-analysis showed that more pronounced hyperaldosteronism, young age, female gender, and larger tumors are the phenotypic features of APA patients with KCNJ5 mutations. No significant differences in blood pressure and serum K+ was found, which suggests that these clinical features do not help in identifying mutated APA patients.