Low renin hypertension

• the renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in sodium and water balance and blood pressure control
  • low-renin hypertension
    • identified by the failure of renin to increase normally with low sodium intake or with volume depletion
  • approximately 30% of patients with essential hypertension have the low-renin variant
    • this variant of hypertension is particularly common among African Americans and Asians - likely to be a consequence of ethnic differences in renal sodium handling and alterations in mineralocorticoid physiology
    • characteristics of patients with low-renin hypertension include
      • increased blood pressure sensitivity to dietary salt intake and changes in plasma volume
      • impaired therapeutic response to angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, or ß-blocking agents
      • enhanced blood pressure responsiveness to calcium channel or aldosterone blockade or to diuretics - there is study evidence of the beneficial blood pressure lowering effects of aldosterone antagonists in this treatment group (1,2)
  • the measurement of aldosterone renin ratio is elevated in patients with low-renin hypertension
    • the presence of an elevated aldosterone ratio leads to a variation in diagnosis and estimated prevalence of primary hyperaldosteronism (2)
      • higher estimates encourage search for adrenal adenomas in patients with elevated ratios of plasma aldosterone to renin
      • it is however more likely that patients with normal plasma K+ and aldosterone belong to the polygenic spectrum of low-renin hypertension rather than have the same monogenic syndrome as classic Conn's
      • the SALT trial investigated whether, in low-renin patients with normal plasma K+ and aldosterone, a thiazide diuretic, bendroflumethiazide, would be as effective as spironolactone in overcoming the Na+ retention and lowering blood pressure
        • this relatively small study in hypertensive patients with a low plasma renin but normal K+ found that bendroflumethiazide 5 mg was as effective as spironolactone 100 mg in lowering blood pressure, despite patients being selected for a previous large fall in blood pressure on spironolactone
          • result differs from that expected in primary hyperaldosteronism - the study authors suggest that this is an arguement against low-renin hypertension including a large, undiagnosed pool of primary hyperaldosteronism
          • however, spironolactone was the more effective natriuretic agent, suggesting that inappropriate aldosterone release or response may still contribute to the Na+ retention of low-renin hypertension

Reference:

• (1) Weinberger MH et al. Effects of eplerenone versus losartan in patients with low-renin hypertension.Am Heart J. 2005 Sep;150(3):426-33.
• (2) Hood SJ et al. The spironolactone, amiloride, losartan, and thiazide (SALT) double-blind crossover trial in patients with low-renin hypertension and elevated aldosterone-renin ratio.Circulation. 2007 Jul 17;116(3):268-75