REPEATED TRANSIENT ANURIA FOLLOWING LOSARTAN ADMINISTRATION IN A PATIENT WITH A SOLITARY KIDNEY

Abstract

We report the case of a 70-year-old hypertensive man with a solitary kidney and chronic renal insufficiency who developed two episodes of transient anuria after losartan administration. He was hospitalized for a myocardial infarction with pulmonary edema, treated with high-dose diuretics. Due to severe systolic dysfunction losartan was prescribed. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria, which lasted eight hours despite high-dose furosemide and amine infusion. One week later, by mistake, losartan was prescribed again and after the second dose of 50 mg, the patient developed a second episode of transient anuria lasting 10 hours. During these two episodes, his blood pressure diminished but no severe hypotension was noted. Ultimately, an arteriography showed a 70–80% renal artery stenosis. In this patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, angiotensin II receptor blockade by losartan probably induced a critical fall in glomerular filtration pressure. This case report highlights the fact that the angiotensin II receptor antagonist losartan can cause serious unexpected complications in patients with renovascular disease and should be used with extreme caution in this setting.

• Solitary kidney
• Renovascular disease
• Losartan
• Angiotensin II receptor antagonist
• Anuria

INTRODUCTION

Angiotensin converting enzyme inhibitors (ACEi) are widely used for the treatment of hypertension, heart failure, and myocardial infarction. Recently, the angiotensin II AT1-receptor (AIIr) antagonist losartan has been developed and acts as an effective antihypertensive agent. In 1997, the ELITE study suggested that losartan may be better than captopril for the treatment of heart failure in elderly patients—with a reduction of mortality and no difference in renal dysfunction [[1]]. Acute renal failure in patients with renovascular disease is a serious side effect of ACEi [[2]]. In this situation, some authors have suggested that AIIr antagonists may cause less deterioration of glomerular filtration than ACEi [3-4]. Rare cases of losartan-induced acute renal failure with conserved diuresis have been reported [5-10]. We report a case of repeated anuria after losartan administration to a patient with renal artery stenosis on a solitary kidney. To our knowledge this is the first case of anuria following losartan reported in the literature.

CASE REPORT

The patient was a 70-year-old Caucasian male with a history of hypertension, vascular disease, and smoking. Three years before, he underwent a right nephrectomy for hypernephroma and thereafter progressively developed chronic renal insufficiency (creatinine ≈170 mol/L). He was hospitalized for a myocardial infarction with pulmonary edema that did not meet the criteria for thrombolysis. A conventional treatment with heparin, aspirin, nitrates, and furosemide was done, followed by the introduction of amlodipine for increasing blood pressure levels. On day five, echocardiography showed a severe systolic dysfunction (ejection fraction 35%). On the basis of the results of the ELITE study [[1]], losartan (Cosaar®) was chosen for the treatment of heart failure. Surprisingly, the first dose of 50 mg of losartan resulted in a sudden anuria which lasted eight hours despite high-dose furosemide and amine infusion (Fig. 1). The beginning of a hemodiafiltration session was under discussion when the diuresis resumed. One week later, the patient had left the intensive care unit. By mistake, losartan was prescribed again and after the second dose of 50 mg the patient developed a second episode of anuria lasting ten hours (Fig. 1). Fortunately, the diuresis fully recovered thereafter. During these two episodes, blood pressure diminished but no severe hypotension was noted (systolic BP ≥ 110 mmHg). Duplex sonography showed a normal-sized left kidney without clear evidence of renal artery stenosis. Afterward, as heart failure remained symptomatic, low-dose captopril was introduced (6.25 mg t.i.d. then 12.5 mg b.i.d.). Captopril caused a slightly lower decrease in BP (systolic BP ≥ 115 mmHg), without modification of the diuresis but with a ≈25% rise of creatinine. Ultimately, an arteriography showed a 70–80% renal artery stenosis which was successfully dilated with a stent placement. Later, a four-vessel coronary bypass was performed. Thereafter, the creatinine stabilized at ≈ 150 mol/L.

Figure 1. Evolution of the diuresis during the two episodes of anuria.

DISCUSSION

Acute renal failure is a well-known side effect of ACEi prescription, occurring particularly in patients with bilateral artery stenosis or low fixed renal blood flow [[1]]. This side effect occurs also with AIIr antagonists prescriptions and, to date, losartan-induced acute renal failure with conserved diuresis has been reported in six patients, two of whom had renovascular disease [5-10]. The present case of repeated anuria following repeated administration of losartan shows a dramatic and unexpected complication caused by this drug in a patient with renal artery stenosis on a solitary kidney. That our patient exhibited the same complication after a new (nonvoluntary) challenge with the drug is a strong argument for the causal role of losartan. This type of complication after losartan prescription has not yet been reported in the literature, but a similar case of sudden transient anuria lasting ≈20 hours has been described after the oral prescription of 100 mg of captopril in a patient having, like the present one, renal artery stenosis on a solitary kidney [[11]].

In our patient, renal artery stenosis combined with heart failure and diuretic therapy certainly resulted in a strong activation of the renin-angiotensin system (RAS). Under such conditions, AIIr blockade by losartan probably induced a critical fall in glomerular filtration pressure. The major role played by activation of the RAS in the response to losartan has been demonstrated in normal volunteers. Losartan induced almost no hemodynamic and renal effects compared to placebo in sodium-replete volunteers, but in salt-deplete volunteers (after dietary salt restriction and diuretic therapy) it caused not only an important lowering of blood pressure, but also a significant mean 70% decrease of the creatinine clearance [[12]].

The subsequent prescription of low-dose captopril to our patient, although associated with a worsening of renal function, did not cause any modification of the diuresis. This difference could not be ascribed to a difference in blood pressure, as no severe hypotension was noted after either drug was administered. Although having similar effects to that of ACEi, AIIr antagonists show two main differences from this latter group. First, they block angiotensin II effects regardless of whether they are produced by ACE- or non ACE-dependent mechanisms and, second, they have no effects on bradykinin metabolism [3-4]. A study in uninephrectomized dogs with renal artery stenosis compared the response to the prescription of captopril and EXP3174, the active metabolite of losartan. For any given change in mean arterial pressure, EXP3174 resulted in a significantly steeper decline in glomerular filtration rate than captopril [[13]]. As EXP3174 is a noncompetitive antagonist of the AII receptors, one can speculate that losartan induces a dose-dependent inhibition of the RAS that is stronger and more difficult to overcome than that due to captopril [[13]]. Alternatively, incomplete ACE inhibition by low-dose captopril, angiotensin II formation through ACE-independent pathways, or the bradykinin-enhancing activity of ACEi may play a protective role under captopril [14-16].

This case report highlights the fact that AIIr antagonists can also cause serious unexpected complications in patients with renovascular disease, particularly in clinical situations where the RAS is strongly activated, and should be used with extreme caution in this setting.