Correspondence
Renal Atrophy Associated with Long-Term Treatment with Indinavir
N Engl J Med 1999; 340:392-393February 4, 1999
- Article
To the Editor:
Indinavir, a human immunodeficiency virus (HIV)–protease inhibitor, improves survival in HIV-infected patients. Although urolithiasis and renal dysfunction are associated with short-term use of indinavir,1,2 no adverse effects have been reported in patients receiving long-term indinavir therapy. We describe two men with hemophilia in whom renal atrophy developed during long-term treatment with indinavir.
The first patient was a 31-year-old, HIV-infected man with hemophilia who received treatment with zalcitabine (dideoxycytidine, 2.25 mg per day) and indinavir (2400 mg orally three times a day). The plasma HIV RNA level fell from 100,000 to less than 400 copies per milliliter; the CD4 count rose from 15 to 221 cells per cubic millimeter. After indinavir was started, persistent pyuria developed, but a urine culture was negative, and protein excretion was normal. Tests for C-reactive protein in serum remained weakly positive after week 12. The serum creatinine level rose gradually from 0.64 to 1.36 mg per deciliter at week 76. Loxoprofen (120 mg per day) was prescribed for arthralgia. Ultrasonographic findings were normal except for increased echogenicity at week 20, but at week 76 ultrasonography revealed bilateral renal atrophy with lobulated contours (Figure 1AFigure 1
Ultrasonograms of the Right Kidney in a Patient with Hemophilia and HIV Infection Who Received Indinavir. and Figure 1B). Radioisotope renography (with technetium-99m–labeled dimercaptosuccinic acid) showed cold spots in both kidneys.The second patient was a 23-year-old man with hemophilia and AIDS who was given indinavir (2400 mg orally three times a day) and didanosine (dideoxyinosine, 200 mg per day). The dose of indinavir was reduced to 1800 mg at week 10 because of hematuria. The plasma HIV RNA level fell from 10,000 to less than 400 copies per milliliter and was undetectable thereafter; the CD4 count rose from 29 to 404 cells per cubic millimeter. The serum creatinine level rose gradually from 0.68 to 2.28 mg per deciliter during 92 weeks of treatment with indinavir. Urinalysis showed pyuria, with no bacteriuria or proteinuria. Tests for C-reactive protein remained weakly positive after week 4. Ultrasonography revealed right renal atrophy. Renal scintigraphy and renography showed multiple patchy defects and a blunted excretory phase in both kidneys.
Eight weeks after indinavir was replaced by nelfinavir in both patients, the serum creatinine levels became normal and the pyuria resolved; however, the shape and size of the kidneys were unchanged.
Patients with AIDS are at increased risk for renal disorders attributable to HIV nephropathy and also to nephrotoxic effects of drug therapy. Tashima et al. reported the intratubular crystallization of indinavir, with potential injury of renal parenchyma.2 These two cases of persistent pyuria and renal atrophy suggest the presence of chronic renal inflammation, possibly due to “crystal pyelonephritis.” Another possible cause is unrecognized obstruction of the ureter by indinavir crystals, possibly with superimposed infection. The absence of proteinuria militates against a contribution of HIV-associated nephropathy to renal injury,3 although nonsteroidal antiinflammatory drugs may enhance the renal toxicity of other agents (an effect that may have been present in the first case). Our findings indicate that patients receiving long-term treatment with indinavir should be carefully monitored for adverse renal effects.
3 ReferencesHideji Hanabusa, M.D.
Hisamichi Tagami, M.D.
Ogikubo Hospital, Tokyo 167-8515, JapanHiroshi Hataya, M.D.
Children's Hospital, Tokyo 204-0024, Japan1
Kopp JB ,Miller KD ,Mican JA , et al. Crystalluria and urinary tract abnormalities associated with indinavir. Ann Intern Med 1997;127:119-125
Web of Science | Medline2
Tashima KT ,Horowitz JD ,Rosen S . Indinavir nephropathy. N Engl J Med 1997;336:138-140
Full Text | Web of Science | Medline3
Rao TK . Clinical features of human immunodeficiency virus associated nephropathy. Kidney Int Suppl 1991;35:S13-S18
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