目的:表观盐皮质激素过量(AME)综合征是一种超罕见的常染色体隐性遗传性肾小管病,由HSD11B2突变引起,导致肾脏盐皮质激素受体过度激活,以早发性低肾素高血压为特征,低钾血症,和慢性肾脏病(CKD)的风险。迄今为止,大多数报告包括很少的病人,没有人描述来自以色列的病人。我们旨在描述来自以色列的AME患者并回顾相关文献。
方法:回顾性队列研究。
方法:临床,实验室,收集患者记录的分子数据。
结果:5例儿童早期肾小球滤过率(eGFR)正常的患者,而两名患者在儿童晚期出现CKD。分子分析揭示了HSD11B2中的两个新的纯合突变。所有患者均表现为严重的高血压和低钾血症。虽然所有患者都出现了肾钙化病,只有一个显示高钙尿症。所有的人都用钾补充剂管理,盐皮质激素受体拮抗剂,和各种抗高血压药物。一名患者在严重高钾血症继发的心脏骤停中幸存下来。在最后的随访中,这5例早期患者表现出正常的eGFR和接近正常的血压,但是两个有高血压并发症。两名患有CKD的患者进展为终末期肾病(ESKD),需要透析和肾移植。
结论:在这份关于两个AME以色列家庭的11年随访报告中,早期肾功能维持长期正常的患者,而那些迟到的人进展到ESKD。然而,尽管早期诊断和治疗,AME通常与疾病或其治疗的严重并发症有关。
OBJECTIVE: Apparent mineralocorticoid excess (AME) syndrome is an ultra-rare autosomal-recessive tubulopathy, caused by mutations in HSD11B2, leading to excessive activation of the kidney mineralocorticoid receptor, and characterized by early-onset low-renin hypertension, hypokalemia, and risk of chronic kidney disease (CKD). To date, most
reports included few patients, and none described patients from Israel. We aimed to describe AME patients from Israel and to review the relevant literature.
METHODS: Retrospective cohort study.
METHODS: Clinical, laboratory, and molecular data from patients\' records were collected.
RESULTS: Five patients presented at early childhood with normal estimated glomerular filtration rate (eGFR), while 2 patients presented during late childhood with CKD. Molecular analysis revealed 2 novel homozygous mutations in HSD11B2. All patients presented with severe hypertension and hypokalemia. While all patients developed nephrocalcinosis, only 1 showed hypercalciuria. All individuals were managed with potassium supplements, mineralocorticoid receptor antagonists, and various antihypertensive medications. One patient survived cardiac arrest secondary to severe hyperkalemia. At last follow-up, those 5 patients who presented early exhibited normal eGFR and near-normal blood pressure, but 2 have hypertension complications. The 2 patients who presented with CKD progressed to end-stage kidney disease (ESKD) necessitating dialysis and kidney transplantation.
CONCLUSIONS: In this 11-year follow-up report of 2 Israeli families with AME, patients who presented early maintained long-term normal kidney function, while those who presented late progressed to ESKD. Nevertheless, despite early diagnosis and management, AME is commonly associated with serious complications of the disease or its treatment.