From KSAP
A 74-year-old retired stock broker with hypertension diagnosed 20 years ago has been treated successfully with extended-release metoprolol 25 mg daily. In the last 6 months, however, the patient noticed occasional lightheadedness on standing, prompting an evaluation that included a normal cardiac stress test and echocardiogram and culminated in a change from metoprolol to valsartan 80 mg daily. The orthostatic symptoms resolved, and blood pressure has remained well controlled. However, his serum creatinine increased following this change.
The patient is concerned with the rise in serum creatinine.
Result Reference Range
Sodium 141 mEq/L 136–145
Potassium 4.8 mEq/L 3.5–5.0
Chloride 106 mEq/L 98–106
Total CO2 23 mEq/L 23–30
Blood urea nitrogen 22 mg/dL 8–20
Creatinine “1.5 mg/dL
(1.2 mg/dL 4 months ago)” 0.7–1.3
Which of the following would be the BEST next step in management?
A Discontinue valsartan and start chlorthalidone
B Recheck serum chemistries in 1 week
C Measure plasma renin activity and aldosterone concentration
D Obtain renal artery duplex ultrasound
E Change valsartan back to metoprolol
Answer & Explanation
B. Recheck serum chemistries in 1 week
The best approach for this patient is to recheck serum chemistries in 1 week to confirm that kidney function is stable. Angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) are associated with a physiologic reduction in intraglomerular pressure, which may lead to a reduction in the glomerular filtration rate (GFR). These agents both decrease arterial pressure by blocking angiotensin’s effect on the vasculature and also decrease vasoconstriction of the efferent arteriole. The resulting rise in the serum creatinine typically occurs within a few days of initiating the medication and stabilizes thereafter. The fall in intraglomerular pressure is believed to underlie the renoprotective effect of these medications, namely by reducing the injurious intraglomerular hypertension. A modest rise in serum creatinine by up to 30% that does not progress is commonly observed and is not associated with any adverse outcome.
Individuals with conditions that result in dependence on the renin-angiotensin-aldosterone system for maintenance of GFR may develop a >30% decline in GFR with the introduction of ACE inhibitors or ARBs. These individuals include patients with macrovascular renal disease such as bilateral renal artery stenosis or microvascular renal disease such as hypertensive nephrosclerosis. If the GFR declines >30% during the first 6–8 weeks of ACE inhibitors or ARBs, the drug should be discontinued, and the above diagnostic possibilities should be considered. The decline in GFR is almost always reversible but occasional cases of persistent worsening of GFR following blockade of the renin-angiotensin-aldosterone system have been reported. In this patient, the rise in serum creatinine is 25% and within the expected range. It would be premature to pursue a diagnosis of renal artery stenosis with renal duplex ultrasound. Measurement of plasma renin activity and aldosterone concentration is a screening test for primary hyperaldosteronism, which is not a diagnostic consideration in this patient.
It would be premature to start a new agent (chlorthalidone) or resume a previously poorly tolerated agent (metoprolol). A repeat measurement of the serum creatinine will help the clinician confirm that the change in GFR is physiologic and not reflective of parenchymal kidney injury. If the serum creatinine is stable, the patient can be reassured that the valsartan-related rise in serum creatinine is expected and may reflect a therapeutic effect of the drug rather than toxicity. Reassurance alone, without repeat serum creatinine measurement, would not be unreasonable in light of the normal urinalysis, but might not satisfy the concerns of this patient.
References:
Garovic VD, Textor SC: Renovascular Hypertension and Ischemic Nephropathy. Circulation 112(9): 1362–1374, 2005
Palmer B: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: What to do if the serum creatinine and/or serum potassium concentration rises. Nephrol Dial Transplant 18(10): 1973–1975, 2003