Management of resistant hypertension
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* J. David Spence

In their review, Padwal and colleagues1 made an interesting and important omission. Variants of Liddle syndrome (genetic mutations affecting the renal tubular epithelial sodium channel, ENac, causing salt and water retention and loss of potassium), are far commoner than most physicians suppose.

Baker and colleagues2 report that a variant of ENac (T594M) was responsible for 5% of hypertension in black patients mainly of Caribbean origin in London, United Kingdom. A different variant, R563Q, was reported in 2003 by Rayner and colleagues;3 this variant is present in 20% of the Khoi San people of the Kalahari, who are not hypertensive with a low sodium intake on the hot, dry Kalahari, but become severely hypertensive when they move to Cape Town, South Africa.4 This variant accounts for 6% of hypertension in black patients in southern Africa, and 9% among Nguni–Zulu residents of southern Africa.4 Although Liddle variants may be more common in black patients,5 a Liddle phenotype was found in 6% of patients attending a hypertension clinic for veterans in Louisiana, of whom 42.7% were African American.6 Surprisingly, the prevalence of a Liddle phenotype was nearly the same as that of primary aldosteronism in that clinic population (6.7%).

Why does this matter? Amiloride was mentioned in the review by Padwal and colleagues1 as an alternative therapy for primary aldosteronism, but it is important to recognize that it is the specific treatment for Liddle variants.2 For that reason, it is important to diagnose Liddle variants among patients with resistant hypertension. The algorithm 1 (available at shown in Appendix [www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.1150014/-/DC1](http://www.cmaj.ca/lookup/suppl/doi:10.1503/cmaj.1150014/-/DC1)) is useful in determining the physiologic drivers of hypertension so that appropriate therapy can be prescribed.

## References

1.  Padwal RS, Rabkin S, Khan N. Assessment and management of resistant hypertension. CMAJ 2014;186:E689–97.
    
    [FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiRlVMTCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czoxMToiMTg2LzE4L0U2ODkiO3M6NDoiYXRvbSI7czoyMjoiL2NtYWovMTg3LzQvMjc4LjIuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

2.  Baker EH, Duggal A, Dong Y, et al. Amiloride, a specific drug for hypertension in black people with T594M variant? Hypertension 2002;40:13–7.
    
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3.  Rayner BL, Owen EP, King JA, et al. A new mutation, R563Q, of the beta subunit of the epithelial sodium channel associated with low-renin, low-aldosterone hypertension. J Hypertens 2003;21:921–6.
    
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4.  Jones ES, Owen EP, Rayner BL. The association of the R563Q genotype of the ENaC with phenotypic variation in Southern Africa. Am J Hypertens 2012;25:1286–91.
    
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5.  Spence JD. Lessons from Africa: the importance of measuring plasma renin and aldosterone in resistant hypertension. Can J Cardiol 2012;28:254–7.
    
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6.  Tapolyai M, Uysal A, Dossabhoy NR, et al. High prevalence of liddle syndrome phenotype among hypertensive US Veterans in Northwest Louisiana. J Clin Hypertens (Greenwich) 2010;12:856–60.
    
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