Acute tubulointerstitial nephritis attributable to indinavir therapy

Jaradat, Majd I.; Phillips, Carrie L.; Yum, Moonahm; Cushing, Herbert E; Moe, Sharon M.

doi:10.1016/s0272-6386(00)70034-5

Cited by 31 publications

(12 citation statements)

References 17 publications

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“…Indinavir crystalluria and nephrolithiasis can present with back or flank pain, dysuria, urinary urgency, and gross hematuria. (88). The pyuria and azotemia resolved in those who discontinued indinavir.…”

Section: Renal Toxicity Of Antiretroviral Agentsmentioning

confidence: 96%

“…Obstructive uropathy with indinavir may be mild and resolve spontaneously or be severe, with bilateral obstruction requiring urologic intervention. Acute or subacute ARF without crystalluria with renal biopsy findings of intratubular and intracellular crystals with chronic interstitial nephritis, interstitial fibrosis, tubular atrophy, and multinucleated histiocytes has also been described (88,89).…”

Section: Renal Toxicity Of Antiretroviral Agentsmentioning

confidence: 99%

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Highly Active Antiretroviral Therapy and the Kidney

Berns

Kasbekar

2006

Clinical Journal of the American Society of Nephrology

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Highly active antiretroviral therapy has dramatically altered the treatment and life expectancy of individuals who are infected with HIV. More than 20 antiretroviral drugs and drug combinations now are available in the United States. Nephrologists need to have an understanding of the pharmacokinetics of antiretroviral medications and the proper dosing of these medications in patients with impaired kidney function. It is also important for nephrologists to be aware of drug-drug interactions that can occur between antiretroviral medications and other medications that they may prescribe, including immunosuppressive medications that are used for renal transplantation, as this becomes more common in HIV-infected patients. Adverse reactions that affect the kidneys and cause fluid-electrolyte complications occur with certain antiretroviral agents, although most are relatively free of nephrotoxicity. This article reviews the clinical pharmacology and dosing modifications of the newer antiretroviral medications in patients with reduced kidney function; important drug-drug interactions involving these medications, particularly with other medications that are likely to be prescribed by nephrologists; and renal toxicities of antiretroviral agents.

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Section: Renal Toxicity Of Antiretroviral Agentsmentioning

confidence: 96%

Section: Renal Toxicity Of Antiretroviral Agentsmentioning

confidence: 99%

Highly Active Antiretroviral Therapy and the Kidney

Berns

Kasbekar

2006

Clinical Journal of the American Society of Nephrology

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“…In addition to common causative agents such as nonsteroidal anti-inflammatory drugs (NSAIDs) and antibacterial antibiotics, patients with HIV infection are commonly exposed to antiretroviral (ARV) and antituberculosis drugs that are known to cause AIN. Furthermore, a variety of ARV drugs such as indinavir, abacavir, and atanazavir have been implicated in the cause of biopsy-proven AIN (4,6,7).…”

mentioning

confidence: 99%

Characteristics of Patients with HIV and Biopsy-Proven Acute Interstitial Nephritis

Parkhie¹,

Fine²,

Lucas³

et al. 2010

Clinical Journal of the American Society of Nephrology

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Results: Of 262 biopsies, 29 (11%) patients who had AIN without evidence of HIV-associated nephropathy were identified. The mean age at the time of biopsy was 47.5 years (range 28 to 71 years), 17 (59%) were men, and 23 (79%) were black. The majority (62%) of patients were on antiretroviral therapy, 59% were current or former intravenous drug users, and 62% had hepatitis C co-infection. Drugs were identified as the cause of AIN in the majority (72%) of cases. Nonsteroidal antiinflammatory drugs were most commonly implicated, followed by sulfamethoxazole/trimethoprim. Antiretroviral therapy was identified as the cause in only three cases. None of the patients presented with the classic triad of fever, rash, and pyuria, and only seven (24%) patients presented with <1 g/d proteinuria.Conclusions: In our series, AIN was prevalent (11%) and was often drug induced. AIN should not be excluded from the differential diagnosis on the basis of absence of the classic clinical triad of fever, rash, and pyuria.

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“…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.…”

Section: Discussionmentioning

confidence: 67%

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

Rossum¹,

Dieleman

Fraaij³

et al. 2002

Pediatrics

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ABSTRACT. Background. Prolonged administration of indinavir is associated with the occurrence of a variety of renal complications in adults. These well-documented side effects have restricted the use of this potent protease inhibitor in children.Design. A prospective study to monitor indinavir-related nephrotoxicity in a cohort of 30 human immunodeficiency virus type 1-infected children treated with indinavir.Methods. Urinary pH, albumin, creatinine, the presence of erythrocytes, leukocytes, bacteria and crystals, and culture were analyzed every 3 months for 96 weeks. Serum creatinine levels were routinely determined at the same time points. Steady-state pharmacokinetics of indinavir were done at week 4 after the initiation of indinavir.Results. The cumulative incidence of persistent sterile leukocyturia (>75 cells/L in at least 2 consecutive visits) after 96 weeks was 53%. Persistent sterile leukocyturia was frequently associated with a mild increase in the urine albumin/creatinine ratio and by microscopic hematuria. The cumulative incidence of serum creatinine levels >50% above normal was 33% after 96 weeks. Children with persistent sterile leukocyturia more frequently had serum creatinine levels of 50% above normal than those children without persistent sterile leukocyturia. In children younger than 5.6 years, persistent sterile leukocyturia was significantly more frequent than in older children. A higher cumulative incidence of persistent leukocyturia was found in children with an area under the curve >19 mg/L*h or a peak serum level of indinavir >12 mg/L. In 4 children, indinavir was discontinued because of nephrotoxicity. Subsequently, the serum creatinine levels decreased, the urine albumin/creatinine ratios returned to zero, and the leukocyturia disappeared within 3 months.Conclusions. Children treated with indinavir have a high cumulative incidence of persistent sterile leukocyturia. Children with persistent sterile leukocyturia more frequently had an increase in serum creatinine levels of >50% above normal. Younger children have an additional risk for renal complications. The impairment of the renal function in these children occurred in the absence of clinical symptoms of nephrolithiasis. Indinavirassociated nephrotoxicity must be monitored closely, especially in children with risk factors such as persistent sterile leukocyturia, age <5.6 years, an area under the curve of indinavir >19 mg/L*h, and a C max >12 mg/L. Pediatrics 2002;110(2). URL: http://www.pediatrics.org/ cgi/content/full/110/2/e19; human immunodeficiency virus, children, indinavir, nephrotoxicity.ABBREVIATIONS. HIV, human immunodeficiency virus; AUC, area under plasma-concentration curve; IQR, interquartile range. I ndinavir is a potent human immunodeficiency virus (HIV)-protease inhibitor that has been used successfully in adults in combination with nucleoside reverse transcriptase inhibitors to suppress infections by HIV-1. Discontinuation of the antiretroviral therapy rapidly results in virologic rebound, decreased immune function, ...

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Acute tubulointerstitial nephritis attributable to indinavir therapy

Cited by 31 publications

References 17 publications

Highly Active Antiretroviral Therapy and the Kidney

Highly Active Antiretroviral Therapy and the Kidney

Characteristics of Patients with HIV and Biopsy-Proven Acute Interstitial Nephritis

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

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