Acute Interstitial Nephritis Secondary to the Administration of Indinavir

Abstract

TO THE EDITOR: Nonphenothiazine antipsychotic-induced hepatotoxicity is rare. 1,2 Risperidone is a nonphenothiazine benzisoxazole derivative that is structurally different from other antipsychotics associated with hepatotoxicity. Although hepatotoxicity is listed in the product information 3 as a potential adverse effect, there have been no reports of hepatotoxicity in patients receiving less than 25 days of therapy. To our knowledge, there are only two published letters 4,5 reporting possible risperidone-induced hepatotoxicity in adults. In the first report, 4 one patient had greater than 6 months' exposure, and a second patient had 6 weeks' exposure to risperidone 6 mg/d; both developed liver enzyme abnormalities consistent with hepatocellular toxicity. The second report 5 described a 54-year-old man with dementia who developed jaundice with an isolated increase in total bilirubin on day 25 after starting risperidone 1 mg bid. We describe suspected drug-induced hepatitis in a man who received only two doses of risperidone 0.5 mg po.Case Report. An 81-year-old white man was admitted to the hospital January 16, 1997, because of a history of paranoid delusions and a significant decline in his level of functioning. His medical history was significant for Parkinson's disease, dementia, depression, hypothyroidism, and peptic ulcer disease. He reported no history of alcoholism. Medications on admission included enteric-coated aspirin, diltiazem, sublingual nitroglycerin, levothyroxine, and doxepin. He had been taking stable dosages of all of these medications for at least 6 months; doxepin was not continued in the hospital. He was prescribed lorazepam prn on January 16, which he continued to receive throughout his hospital stay. Baseline liver function test results on admission were normal, with aspartate aminotransferase (AST) 20 units/L (normal <37), alanine aminotransferase (ALT) 13 units/L (<40), alkaline phosphatase 90 units/L (40-120), and total bilirubin 0.7 mg/dL (0.1-1.2). Risperidone was started on January 20. He received two doses of 0.5 mg po. On January 21, 1997, he was noted to be jaundiced and the risperidone was discontinued. Other than mild right upper quadrant pain, the patient reported no other symptoms. Similarly, physical examination revealed jaundice and some tenderness on palpation of the right upper quadrant. Liver function test results at that time revealed AST 434 units/L, ALT 101 units/L, total bilirubin 3.6 mg/dL, and alkaline phosphatase 244 units/L. Complete blood count, electrolytes, and serum creatinine were all normal. An ultrasound scan of the abdomen on January 22, 1997, revealed mild splenomegaly (14.1 cm) and small gallstones without any dilation of the biliary tree. Repeat liver function test results 2 weeks later (February 2, 1997) had returned to baseline (AST 19 units/L, ALT 5 units/L, alkaline phosphatase 114 units/L). Similarly, follow-up liver enzymes on April 17 and 24 were normal. Viral hepatitis serology (hepatitis A, B, and C) was negative. He continued to do well and re...

The Natural History of Leukocyturia Associated with Indinavir Treatment in HIV+ Individuals

“…The association between significant leukocyturia and indinavir-related renal damage as reported in the literature [10,14,[19][20][21]25], as well as the present findings of recurrent severe leukocyturia, may warrant a change in the management of these subjects to prevent progression of renal damage. These changes might include increased water intake, combination of a reduced dose of indinavir with another HIV-1 protease inhibitor and, perhaps as a last resort (in the presence of progressive severe renal failure), consideration to alter antiretroviral treatment.…”

“…This is the first longitudinal study that consistently demonstrates the relationship between indinavir treatment and urine abnormalities, leukocyturia in particular. While several reports of indinavir-related nephropathy mention the presence of leukocyturia [10,14,[19][20][21]25], surprisingly there are no reports of prospective or longterm studies of such populations.…”

Persistent Sterile Leukocyturia Is Associated With Impaired Renal Function in Human Immunodeficiency Virus Type 1-Infected Children Treated With Indinavir

“…This is supported by the pathologic finding of tubulointerstitial nephritis in patients on therapy with indinavir. 4,24,25 The prevalence of persistent leukocyturia in adults screened on the same nephrotoxicity monitoring program was 22% (J. P. Dieleman, personal communication, September 10, 2001), which is substantially lower than we observed in children. One might hypothesize that indinavir crystals more easily congest in the small tubuli of young children which may lead to a higher incidence of nephrolithiasis.…”

“…Indinavir crystals may illicit an inflammatory response in the tubules, leading to sterile leukocyturia and renal insufficiency. [2][3][4][5][6][7] To minimize renal side effects of indinavir, an increased fluid intake is advised. 8 The incidence of indinavir-associated nephrolithiasis in adults varies from 4% to 43%.…”

Miscellaneous Stone Types

“…3), which coalesce into radial or striated aggregates and lead to tubular obstruction and stones [5,36,37]. This phenomenon also explains the reported incidence of acute interstitial nephritis with intratubular crystal deposition [41,42,[45][46][47]. Risk factors for indinavir stone formation include volume depletion, inadequate fluid intake, and concomitant use of medications that raise indinavir serum levels.…”