Olmesartan associated with acute renal failure in a patient with bilateral renal artery stenosis

Abstract

In patients with renal artery stenosis (RAS), the inhibition of renin-angiotensin-aldosterone system can cause deterioration of renal function. Here we present a 75-year-old man who developed acute renal failure after olmesartan treatment. Following discontinuation of olmesartan, his renal functions normalized. His renal Doppler ultrasonography and renal angiography showed findings consistent with bilateral RAS. In this case, unlike those previously reported, renal failure developed with olmesartan for the first time and after only a single dose, which is thought to be a new, safe, and tolerable antihypertensive agent. This is a well-defined effect of angiotensin-converting enzyme inhibitors, in patients with RAS. Also with the increasing use of angiotensin II receptor blockers (ARBs), renal failure associated with ARBs in patients with RAS is rising. The use of olmesartan also requires caution and close follow-up of renal functions for patients who have risk factors.

Keywords:

• olmesartan
• renal artery stenosis
• acute renal failure

INTRODUCTION

The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of arterial blood pressure and local hemodynamics. Indications for the use of angiotensin-converting enzyme inhibitors (ACEIs) are increasing that include hypertension, chronic heart failure (CHF), myocardial infarction, diabetic nephropathy, and proteinuric renal disease.

Although ACEIs reduce angiotensin II production, the suppression is not complete or permanent because alternative pathways, particularly involving chymase, unaffected by ACEIs continue to produce angiotensin II. In contrast, angiotensin II receptor blockers (ARBs) directly prevent angiotensin II from exerting its effects by blocking it from binding to angiotensin II type I receptors. In renal hypoperfusion, angiotensin II increases efferent arteriolar resistance, which in turn increases capillary hydrostatic pressure, thereby maintaining the glomerular filtration rate (GFR) despite decreased renal perfusion.¹

Although ACEIs are generally well tolerated, concerns about such adverse effects as cough and angioedema have prompted development of alternative therapies that have similar beneficial effects on the RAAS with a reduced risk of adverse effects. ARBs may gradually replace ACEIs in clinical practice because of the reduced number of side effects.

Olmesartan medoxomil, the newest member of this drug class, is a highly potent ARB that selectively and competitively inhibits the angiotensin II type 1 receptor.² Several clinical studies suggested the efficacy, safety, and tolerability of olmesartan medoxomil in patients with mild to moderate hypertension.^3,4

We report a case of reversible deterioration in renal function after treatment with the ARB olmesartan in a patient with bilateral renal artery stenosis (RAS).

CASE REPORT

A 75-year-old man was admitted to our hospital with the complaint of progressive shortness of breath and lower extremity swelling for 1 week. His medical history was significant for hypertension, coronary artery disease, and CHF. He was using isosorbide-5-mononitrate 120 mg/day, doxazosin 4 mg/day, furosemide 40 mg/3 days/week, and acetylsalicylic acid 100 mg/day. On admission, physical examination revealed a blood pressure of 150/90 mmHg, pulse of 94 beats per minute, and temperature of 36.8°C. His chest auscultation revealed decreased breath sounds at the left base and breath sounds were not heard at the right base. His heart rate and rhythm were regular, with no murmurs, rubs, or gallops. His extremities had 1 (+) pitting edema bilaterally. Abnormal laboratory values at admission were as follows: hemoglobin 12.5 g/dL (125 g/L), hematocrit 35.6%, erythrocyte sedimentation rate 42 mm/h, urea 60 mg/dL (21.4 mmol/L), creatinine 1.7 mg/dL (150 μmol/L), and brain natriuretic peptide 830 pg/mL. On admission, his electrocardiography showed normal sinus rhythm, right bundle brunch block, and non-specific ST-T wave changes. His chest radiography revealed cardiomegaly and bronchovascular congestion. His echocardiography 5 months ago revealed an ejection fraction of 48%, segmental wall motion impairment and mild mitral regurgitation.

After treating his acute exacerbation of CHF with intravenous furosemide his treatment for hypertension and CHF were regulated as amlodipine 10 mg/day, isosorbide-5-mononitrate 120 mg/day, digoxin 0.25 mg/day, doxazosin 4 mg/day, and acetylsalicylic acid 100 mg/day. With this treatment, his creatinine levels decreased to 1.4 mg/dL (124 μmol/L). Because of failure to achieve adequate blood pressure control during this therapy, olmesartan 40 mg/day was started. After first dose of olmesartan, the patient's creatinine levels increased to 3.1 mg/dL (274 μmol/L). Before the initiation of olmesartan, the patient's urine output was approximately 1300–1500 mL/day, but decreased to 300 mL/day by the beginning of olmesartan therapy. His potassium levels also rose to 5.2 mmol/L, which was normal until olmesartan therapy admission. Then olmesartan therapy was stopped and doxazosin was increased to 8 mg/day, metoprolol 50 mg/day was added because of poorly controlled hypertension. On his abdominal ultrasonography, the left and right kidneys were measured as 98 and 86 mm in length, respectively, with normal parenchyma echogenicity. The left and right kidney's parenchymal thicknesses were 15 and 14 mm, respectively.

Because of patient's uncontrolled hypertension, renal Doppler ultrasonography was performed with the suspicion of RAS. His renal Doppler ultrasonography showed the findings consistent with bilateral RAS. Finally, the diagnosis of RAS was confirmed with renal angiography. Although catheterization of left renal artery was difficult because of atherosclerotic plaques, nearly 30% stenosis was found in both of the renal arteries. Based on these findings a diagnosis of acute renal failure associated with olmesartan was made. After the discontinuation of olmesartan his serum creatinine levels decreased gradually and were 1.2 mg/dL (106 μmol/L) on his discharge. His blood pressures were within normal ranges as well.

DISCUSSION

Inhibition of the RAAS constitutes the basis of modern therapy in the myocardial infarction and heart failure patient. Several mechanisms contribute to the beneficial effects of RAAS inhibition in cardiovascular and renal therapy, including limitation of cardiac hypertrophy and fibrosis, reduction of ventricular wall stress from vasodilation, and decreased fluid retention, central sympatholysis, and thrombogenic and fibrinolytic effects. Thus, both of ACEIs and ARBs decrease mortality in patients with CHF. However, these patients often have concurrent atherosclerotic disease, and RAAS inhibition may cause detrimental outcomes when underlying RAS is present.

RAS is a disease that commonly occurs as a result of atherosclerosis of the renal arteries. Consequently, blood flow to kidney is reduced and the RAAS is activated in an attempt to maintain renal blood flow. The mechanism of the RAAS in regulation of renal function is believed primarily to be due to the effect of angiotensin II on the efferent arteriolar tone keeping the pressure relatively constant in the glomerulus and thereby keeping GFR constant over a wide range of perfusion pressures.⁵ In patients sensitive to reduced renal blood flow, abolition of this response by an ACEI or an ARB may result in acute renal failure. Such patients include those with bilateral RAS, renal impairment, severe CHF, and severe sodium and volume depletion because their renal function is often angiotensin dependent. Our patient developed rapidly progressive renal insufficiency, after only a single dose of olmesartan, perhaps because of the presence of both bilateral RAS and volume depletion associated with intensive diuretic therapy.

It is well established that ACEIs should be avoided in patients with critical RAS. In contrast, this is not as well established with respect to ARBs. Over the past years with the increase of these agents usage, several cases have shown that renal function may be impaired if an ARB is used in patients with RAS,^6,7 but there are still some other cases reporting the safety of ARBs in patients with RAS. However, to our knowledge this is the first case report with acute renal failure after olmesartan treatment.

Considering that in our case renal failure improved only after a single dose of olmesartan, renal function should be measured sufficiently often after initiation of therapy with ARBs particularly in patients with risk factors such as atherosclerotic disease or concurrent diuretics use, to detect a deterioration in renal function at an early stage before acute renal failure is established and dialysis required.

If the serum creatinine rises, the agent should be stopped immediately and clinicians should be aware of the possibility of RAS. It is impractical to suggest that all such patients should have invasive imaging of the renal circulation or isotope renography before and after institution of ACEI. But renal Doppler ultrasonography can be recommended at least for patients with RAS suspicion including concurrent atherosclerotic diseases and who have uncontrolled blood pressure despite multiple antihypertensive drugs before the initiation of ARBs.

In conclusion, we report this case to emphasize that ARBs including olmesartan, the newest member of this group, can result in acute renal failure, especially in patients with atherosclerotic risk factors and concomitant drug use, so these patients should be monitored closely.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.