Review Question - QID 106863

The patient's symptoms began shortly after starting lisinopril, an ACE inhibitor (ACEI). ACEIs cause renal efferent arteriole vasodilation and a decrease in GFR, which can precipitate renal failure in predisposed individuals. This patient's response to lisinopril is suggestive of underlying renal disease such as bilateral renal artery stenosis.

ACEIs function by inhibiting the formation of angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II (ATII) works to increase blood pressure by causing vasoconstriction and increasing renal sodium resorption. ATII also causes vasoconstriction of renal efferent arterioles, which serves to maintain GFR in the setting of decreased renal perfusion as with systemic vasoconstriction. Patients with bilateral renal artery stenosis are dependent on this effect of ATII on the efferent arterioles for maintenance of an adequate GFR. Initiation of an ACEI in these patients can thus lead to worsening of renal function.

Bicket describes the indications for ACEI use. ACEIs have proven beneficial for management of hypertension, congestive heart failure, myocardial infarction, left ventricular dysfunction, and diabetic nephropathy via randomized control trials. ACEIs have also been demonstrated to be effective compared to other antihypertensive agents in delaying worsening of renal disease in patients with non-diabetic renal insufficiency. Adverse effects of ACEI use include hypotension, cough, hyperkalemia, and renal insufficiency.

Piecha et al. describe the role of ACEI in the clinical course and management of patients with renal artery stenosis. Use of ACEIs is approved in patients with unilateral renal artery stenosis with careful monitoring of creatinine and GFR. However, ACEIs are contraindicated in patients with bilateral renal artery stenosis given the increased risk of causing a decline in renal function. Elevations in creatinine resulting from ACEI use typically resolve on discontinuation of the drug.

Illustration A shows the hemodynamic effects of prostaglandins and angiotensin II on renal afferent and efferent arterioles, respectively. The effects of prostaglandin inhibition by NSAIDS or angiotensin II inhibition by ACEIs are depicted. (RPF = renal plasma flow, FF = filtration fraction, FF = GFR/RPF)

Incorrect Answers:
Answer 1: NSAIDs cause vasoconstriction of afferent arterioles via inhibition of prostaglandin synthesis, leading to a decreased GFR.
Answer 2: While isolated renal afferent arteriole vasodilation leads to increased GFR, it is not a change that occurs in response to ACE inhibition.
Answer 3: Stimulation by angiotensin II leads to renal efferent arteriole vasoconstriction and an increased GFR. This effect of angiotensin II is disrupted by ACE inhibitors.
Answer 5: This statement is false; isolated renal efferent arteriole vasodilation results in a decreased GFR.