Correspondence
Ritonavir and Renal Failure
N Engl J Med 1997; 336:138January 9, 1997
- Article
To the Editor:
Ritonavir (Norvir, Abbott Laboratories), a protease inhibitor used to treat people with human immunodeficiency virus (HIV) infection, reportedly has no adverse effects on renal function.1,2 We describe a patient in whom acute renal failure developed shortly after the start of treatment with ritonavir.
The patient was a 40-year-old man with HIV infection and stable chronic renal failure. His kidney disease was thought to be due to a horseshoe kidney and to glomerular disease of unknown cause, manifested by an episode of proteinuria in the nephrotic range and, more recently, by the excretion of 1 to 2 g of protein per day. Two months before the patient's admission, his blood urea nitrogen level was 37 mg per deciliter and his serum creatinine level was 2.2 mg per deciliter; these values had remained stable for over two years. His medications included nifedipine, zidovudine, and lamivudine. He was not taking any over-the-counter medications or nonsteroidal antiinflammatory drugs.
Two days after the start of treatment with ritonavir (400 mg twice a day), he had dyspnea on exertion, nausea, anorexia, and declining urinary volume. Ritonavir was discontinued after he had taken a total of 4 g. Fluid overload was evident on the basis of elevated jugular venous pressure, pedal edema, liver tenderness, bibasilar rales, and an oxygen saturation of 88 percent when the patient breathed room air. In other respects his physical examination was normal. The results of laboratory tests on admission were as follows: sodium, 138 mmol per liter; potassium, 4.6 mmol per liter; chloride, 94 mmol per liter; total carbon dioxide, 27 mmol per liter; blood urea nitrogen, 76 mg per deciliter; serum creatinine, 6.1 mg per deciliter; serum albumin, 3.4 mg per deciliter; liver function, normal to slightly elevated; white cells, 9600 per cubic millimeter; hematocrit, 28.4 percent; and platelets, 299,000 per cubic millimeter. Urinalysis revealed 2+ proteinuria; a few red cells, a few renal tubular epithelial cells, and several granular casts per high-power field; and a urinary protein:creatinine ratio of 0.6. A chest film revealed venous congestion, and the electrocardiogram was within normal limits. An echocardiogram revealed normal systolic function and a normal ejection fraction and the absence of abnormalities of regional wall motion or pericardial effusion. The patient was treated with intravenous furosemide; over a four-day period, the serum creatinine level declined to 3.5 mg per deciliter. Two weeks later the levels of blood urea nitrogen and serum creatinine had returned to base line.
We believe the acute renal failure in this patient was caused by ritonavir. Whether the patient was particularly susceptible because of his underlying chronic renal failure is unknown.
2 ReferencesSumant Chugh, M.D.
Boston Medical Center, Boston, MA 02118Richard Bird, M.D., M.P.H.
Bowdoin Street Health Center, Dorchester, MA 02122Edward A. Alexander, M.D.
Boston Medical Center, Boston, MA 021181
Danner SA ,Carr A ,Leonard JM , et al. A short-term study of the safety, pharmacokinetics, and efficacy of ritonavir, an inhibitor of HIV-1 protease. N Engl J Med 1995;333:1528-1533
Full Text | Web of Science | Medline2
Markowitz M ,Saag M ,Powderly WG , et al. A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection. N Engl J Med 1995;333:1534-1539
Full Text | Web of Science | Medline
Author/Editor Response
Spokespersons for Abbott Laboratories reply:
To the Editor: Chugh et al. describe a patient with HIV infection and chronic renal insufficiency who presented with worsening renal function and fluid overload coincident with ritonavir therapy. Although the patient's chronic renal insufficiency is described as stable, the most recent creatinine determination was made two months before the start of ritonavir treatment. The exact timing of the clinical and laboratory evaluations of renal status is unclear, which complicates an understanding of the contributions of ritonavir and preexisting renal disease to the patient's subsequent decline in renal function.
As the ritonavir package insert states,1 less than 2 percent of all patients receiving ritonavir in phase 2–3 clinical studies have had renal failure. In ongoing clinical experience there have been sporadic reports of renal insufficiency. The majority have involved patients who have advanced HIV disease or who are taking multiple medications concomitantly, including those with known nephrotoxic effects. Some reports describe dehydration, usually accompanied by gastrointestinal symptoms, which may be associated with renal insufficiency.
1 ReferencesJohn M. Leonard, M.D.
Margo Heath-Chiozzi, M.D.
Abbott Laboratories, Abbott Park, IL 60064-3500- Citing Articles (23)
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