Resolution of hypertension during pregnancy in familial hyperkalemia and hypertension with the WNK4 Q565E mutation

• Published in: American journal of obstetrics and gynecology Vol. 192; no. 2; pp. 598 - 603
• Main Authors: Mayan, Haim, Mouallem, Meir, Shaharabany, Miriam, Pauzner, Rachel, Farfel, Zvi
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA Mosby, Inc 01.02.2005; Elsevier
• Subjects: Adult; Biological and medical sciences; Familial hyperkalemia and hypertension; Female; Gynecology. Andrology. Obstetrics; Humans; Hyperkalemia; Hyperkalemia - genetics; Hyperkalemia - physiopathology; Hypertension - genetics; Hypertension - physiopathology; Hypertension during pregnancy; Medical sciences; Middle Aged; Mutation; Pregnancy; Pregnancy Complications, Cardiovascular - physiopathology; Protein-Serine-Threonine Kinases - genetics; Pseudohypoaldosteronism type II; WNK kinase; Hypertension during pregnancy; Hyperkalemia; Pseudohypoaldosteronism type II; Familial hyperkalemia and hypertension; WNK kinase; Hypertension; Hydroelectrolytic balance disorder; Enzyme; Transferases; Gynecology; Cardiovascular disease; Inorganic element; Obstetrics; Hypertension during pregnancy Familial hyperkalemia and hypertension Pseudohypoaldo- steronism type II Hyperkalemia WNK kinase; Pregnancy; Hyperkaliemia; Metabolic disorder; Kinase; Female; Genetics; Mutation; Potassium
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2004.07.020

Secondary hypertension during pregnancy usually carries high maternal and fetal morbidity and mortality rates. A rare form of monogenic hypertension is familial hyperkalemia and hypertension, which is caused by mutations in the kinases WNK1 or WNK4 and other unknown molecular defects. The purpose of the study was to examine the course of pregnancy in hypertensive women with familial hyperkalemia and hypertension. We prospectively studied 2 pregnancies of a woman with familial hyperkalemia and hypertension and the Q565E WNK4 mutation (pregnancies 1 and 2) and retrospectively studied the course of 2 pregnancies in another woman who was an affected member of this largest family described in the literature. Both women had hypertension (170-190/105-110 mm Hg), hyperkalemia (5.3-6.0 mmol/L), and hypercalciuria, all of which were well controlled by thiazides. During pregnancies, thiazides were discontinued; throughout the pregnancy, the blood pressure remained normal at 120 to 130/75 to 85 mm Hg; however, hyperkalemia and hypercalciuria, which were documented in pregnancies 1 and 2, persisted. Renin and aldosterone levels (which were measured in pregnancies 1 and 2) rose towards their end. Four normal infants were born. A woman with familial hyperkalemia and hypertension of unknown molecular defect who had 2 pregnancies with hypertension exacerbation and premature deliveries was described previously. In familial hyperkalemia and hypertension with the WNK4 mutation, pregnancy ameliorates hypertension; however, hyperkalemia and hypercalciuria persist. This dissociation may shed light on the pathogenesis of familial hyperkalemia and hypertension, on pregnancy-related hypertension, and on the mechanism of action of WNK4 kinase, a major regulator of cellular ion transport.