It should also be noted that despite theoretical implications of using aliskerin in combination with ACE-I and ARBs to treat “renin and aldosterone escape” particularly in patients with proteinuria [61, 62], studies have reported a significant increase in the adverse effect profile, namely hyperkalemia, hypotension, and renal failure especially in patients with preexisting CKD [62–64]. Here, ACE is linked to acute kidney injury.