Familial hyperkalemic hypertension: hyperkalemia not hypertension defines dominant KLHL3 disease and may permit earlier recognition and tailored therapy.
Familial hyperkalemic hypertension: hyperkalemia not hypertension defines dominant KLHL3 disease and may permit earlier recognition and tailored therapy.
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家族性高钾血症性高血压：高钾血症而非高血压定义了 KLHL3 疾病的主导地位，并且可能允许早期识别和定制治疗。
DOI：
10.1007/s40620-021-01217-5
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发表时间：
2022
影响因子：
3.4
通讯作者：
Thomas,ChristieP
中科院分区：
文献类型：
--
作者：
Sambharia,Meenakshi;Gattineni,Jyothsna;Noureddine,Lama;Mansilla,MAdela;Thomas,ChristieP
一名56岁男性，患有复发性房颤和高钾血症，被转诊至肾遗传学诊所（RGC）。显示了他的血清肌酐、钾和碳酸氢盐水平，以及他的尿钙/肌酐比值和血压（图1，表1）。肾素和醛固酮水平较低，分别为0.1 ng/ml/hr和6.1 ng/dl。他的高钾血症多年来一直用呋塞米40 mg和聚苯乙烯磺酸钠（SPS）30 mg治疗无效。他的父母和多个兄弟有高血压家族史，但没有高钾血症。患者女儿有长期高钾血症病史，无高血压。患者接受了肾基因组（KidneySeq™）的基因检测，结果显示KLHL 3：NM 001，257，194：c中存在杂合、错义变体。1487G> A，p.Arg496His（图2）。根据美国医学遗传学学会（ACMG）标准（PM2、PM 5、PP 2、PP 3、PP 5），该变异体被归类为可能的致病性。在其他5个常染色体显性遗传家族性高钾血症（FHHt）家族中报告了这种错义变体[1，2]。呋塞米转换为氯噻酮，SPS停药。高钾血症在后续检测中消退（图1，表1）。血压继续正常。
A 56-year-old male with recurrent atrial fibrillation and hyperkalemia was referred to the Renal Genetics Clinic (RGC). His serum creatinine, potassium, and bicarbonate levels, as well as his urine calcium to creatinine ratio and blood pressures are shown (Fig. 1, Table 1). Renin and aldosterone levels were low at 0.1 ng/ml/hr and 6.1 ng/dl, respectively. His hyperkalemia had been unsuccessfully treated with furosemide 40 mg and sodium polystyrene sulfonate (SPS) 30 mg daily for years. Family history was positive for hypertension in his parents and multiple brothers, although none had hyperkalemia. The patient’s daughter had a longstanding history of hyperkalemia without hypertension. The patient underwent genetic testing with a renal gene panel (KidneySeq™) which revealed a heterozygous, missense variant in KLHL3: NM 001,257,194: c. 1487G> A, p. Arg496His (Fig. 2). Based on American College of Medical Genetics (ACMG) criteria (PM2, PM5, PP2, PP3, PP5) this variant was classified as likely pathogenic. This missense variant has been reported in 5 other families with autosomal dominant Familial Hyperkalemic Hypertension (FHHt)[1, 2]. Furosemide was switched to chlorthalidone, and SPS was discontinued. Hyperkalemia resolved on subsequent testing (Fig. 1, Table 1). Blood pressure continued to be normal.