All CNIs increase the risk of hyperkalemia [23], especially after adding a renin–angiotensin–aldosterone-system blocker, such as ACE-I or ARB [24]: the underlying mechanisms may rely on the decreased efficacy of loop diuretics (like furosemide) [25], the activation of the sodium-chloride co-transporter [26, 27], and decreased ROMK channel activity [28]. The gene discussed is REN; the disease is Hyperkalemia.