Nephrology

ACE Inhibitors & ARBs in Renal Disease song

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ACE Inhibitors & ARBs in Renal Disease

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ACE inhibitors (e.g., lisinopril) and ARBs (e.g., losartan) are first-line agents for diabetic nephropathy and proteinuric chronic kidney disease due to their ability to reduce intraglomerular pressure by dilating the efferent arteriole.
The mechanism involves blocking angiotensin II–mediated efferent vasoconstriction, thereby lowering glomerular filtration pressure and reducing proteinuria independent of systemic blood pressure effects.
ACE inhibitors block the conversion of angiotensin I to angiotensin II and also prevent bradykinin degradation; accumulated bradykinin causes the classic dry cough and, rarely, angioedema.
ARBs block the AT1 receptor directly and do not affect bradykinin levels, making them the preferred alternative when ACE inhibitor–induced cough or angioedema occurs.
Both drug classes are contraindicated in bilateral renal artery stenosis because blocking efferent dilation in the setting of reduced afferent flow causes an acute, severe drop in GFR.
A rise in serum creatinine of up to 30% above baseline after initiating an ACE inhibitor or ARB is acceptable and expected; an increase greater than 30% should prompt evaluation for renal artery stenosis or volume depletion.
Hyperkalemia is a key adverse effect due to reduced aldosterone secretion; risk is highest in patients with pre-existing CKD, type IV renal tubular acidosis (hyporeninemic hypoaldosteronism), or those on potassium-sparing diuretics.
ACE inhibitors and ARBs are absolutely contraindicated in pregnancy (Category X/formerly D) due to fetal renal dysgenesis, oligohydramnios, and neonatal renal failure — collectively called ACE inhibitor fetopathy.
Combination therapy with an ACE inhibitor plus an ARB (dual RAAS blockade) is not recommended due to increased risk of hyperkalemia, hypotension, and acute kidney injury without additional cardiovascular or renal benefit (per ONTARGET trial).
In heart failure with reduced ejection fraction (HFrEF) complicating CKD, ACE inhibitors/ARBs reduce proteinuria and provide mortality benefit, but dose reduction is required as GFR falls below 30 mL/min/1.73 m².