Correspondence

Losartan-Induced Azotemia in a Diabetic Recipient of a Kidney Transplant

N Engl J Med 1996; 334:1271-1272May 9, 1996

Article

To the Editor:

In patients with diabetic nephropathy, angiotensin-converting–enzyme (ACE) inhibitors reduce blood pressure and the progression of nephropathy,1 but approximately 10 percent of patients have side effects that cause the discontinuation of ACE-inhibitor therapy.2 Losartan is an angiotensin II–receptor antagonist that may have similar efficacy but fewer side effects.2 We describe a patient in whom first enalapril and then losartan induced renal insufficiency.

A 46-year-old-man who had had insulin-dependent diabetes mellitus since the age of 6 years underwent combined pancreas and kidney transplantation at the age of 40, but both organs had to be removed because of severe rejection reactions. After two years of maintenance hemodialysis, he received a haplo-identical renal transplant that functioned well (serum creatinine concentration, 1.6 mg per deciliter), and a regimen of insulin, atenolol, nifedipine, cyclosporine, azathioprine, furosemide, and prednisone was begun. Because of unsatisfactory blood-pressure control, enalapril (40 mg per day) was added. Renal function deteriorated during the next six weeks. Because of the development of intravascular volume overload, hyperkalemia, and an increase in the serum creatinine concentration (to 3.7 mg per deciliter), hemodialysis was performed. Enalapril was discontinued, after which the patient's serum creatinine concentration declined to 1.7 mg per deciliter. Blood-pressure control was inadequate (188/90 mm Hg) during the next 15 months, despite therapy with other antihypertensive drugs. Therefore, treatment with losartan (50 mg per day) was begun. After some reduction in blood pressure (to 150/90 mm Hg), the dose of losartan was increased to 100 mg per day. The patient's serum creatinine concentration increased to 2.3 mg per deciliter after two weeks and to 3.4 mg per deciliter after five weeks, at which time losartan was discontinued. One week later the serum creatinine concentration was 1.9 mg per deciliter. In addition, hyperkalemia (serum potassium, 7.3 mmol per liter) developed during treatment with enalapril and occurred transiently (5.7 mmol per liter) during treatment with losartan.

Although the mechanisms of action of enalapril and losartan differ — the former interferes with the synthesis of angiotensin II and the latter inhibits its action — the net effects of the drugs on renal hemodynamics and kidney function are similar.3 Therefore, in patients who are susceptible to reduced renal plasma flow when treated with an ACE inhibitor, it is not surprising that a similar reaction is induced by losartan. ACE inhibitors may also decrease the glomerular filtration fraction by inducing an increase in bradykinin, an action not shared by losartan.4 Recognition of the possibility of losartan-induced azotemia suggests that in transplant recipients whose serum creatinine concentrations increase during treatment it may be prudent to delay allograft biopsy while discontinuing the drug and monitoring the patient to ensure that the azotemia subsides.

Linda S. Cohen, R.N.
Eli A. Friedman, M.D.
State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203

4 References

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Citing Articles (5)

Citing Articles

1. 1

   Nukhet Bavbek, Benan Kasapoglu, Ayse Isik, Ayse Kargili, Ismail Kirbas, Ali Akcay. (2010) Olmesartan associated with acute renal failure in a patient with bilateral renal artery stenosis. Renal Failure 32:9, 1115-1117
   CrossRef

2. 2

   Domenic A Sica, Todd W B Gehr, Siddhartha Ghosh. (2005) Clinical Pharmacokinetics of Losartan. Clinical Pharmacokinetics 44:8, 797-814
   CrossRef

3. 3

   Jacques-Olivier Maillard, Eric Descombes, Gilbert Fellay, Claude Regamey. (2001) REPEATED TRANSIENT ANURIA FOLLOWING LOSARTAN ADMINISTRATION IN A PATIENT WITH A SOLITARY KIDNEY. Renal Failure 23:1, 143-147
   CrossRef

4. 4

   Eric Descombes, Gilbert Fellay. (2000) END-STAGE RENAL FAILURE AFTER IRBESARTAN PRESCRIPTION IN A DIABETIC PATIENT WITH PREVIOUSLY STABLE CHRONIC RENAL INSUFFICIENCY. Renal Failure 22:6, 815-821
   CrossRef

5. 5

   &NA;. (1996) Enalapril/losartan potassium. Reactions Weekly &NA;:601, 7
   CrossRef