Diffuse Tubulointerstitial Nephritis Accompanied by Renal Crystal Formation in an HIV-infected Patient Undergoing Highly Active Antiretroviral Therapy

Kanzaki, Go; Tsuboi, Nobuyuki; Miyazaki, Yoichi; Yokoo, Takashi; Utsunomiya, Yasunori; Hosoya, Tatsuo

doi:10.2169/internalmedicine.51.7093

Cited by 17 publications

(10 citation statements)

References 25 publications

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“…Both agents are also associated with significant tubulointerstitial disease and increased risk for incident CKD (52). The use of atazanavir in conjunction with ritonavir as a booster has the potential of increasing the risk for the development of granulomatous interstitial nephritis (53)(54)(55). Similar to pharmacoenhancers, these agents are not recommended in those undergoing organ transplantations because of the significant drug-drug interactions with calcineurin inhibitors and mammalian target of rapamycin inhibitors (5,56).…”

Section: Protease Inhibitors (Pis)mentioning

confidence: 99%

Clinical Pharmacology in HIV Therapy

Atta

Seigneux

Lucas

2018

CJASN

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The success of combination antiretroviral therapy in the treatment of HIV-1-positive individuals has shifted clinical attention toward combination antiretroviral drug regimens that optimize tolerability, long-term safety, and durable efficacy. Wherever patients have access to treatment, morbidity and mortality are increasingly driven by non-HIV-associated comorbidities, which may be observed earlier than in age-matched controls and despite the best available combination antiretroviral therapy. Similarly, HIV-1-positive individuals are now diagnosed and treated earlier with anticipated lifelong therapy. The contribution of specific antiretroviral agents to long-term morbidity and mortality is dependent on the pharmacologic characteristics of these agents, and it is increasingly important in this context.

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Section: Protease Inhibitors (Pis)mentioning

confidence: 99%

Clinical Pharmacology in HIV Therapy

Atta

Seigneux

Lucas

2018

CJASN

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“…In particular, atazanavir boosted by ritonavir (ATV/r) may increase TDF concentrations when these two drugs are co-administered and this could aggravate renal damage [ 3 , 4 ]. Moreover, some degrees of acute and chronic interstitial nephritis with crystal deposition were described in patients receiving ATV plus TDF [ 5 , 6 ] and ATV could induce acute tubular injury and nephrolithiasis even without TDF administration [ 7 ]. So, it has to be seen whether renal damage occurring during TDF is reversible after TDF withdrawal, in particular when ATV/r is prescribed.…”

Section: Introductionmentioning

confidence: 99%

Exploratory Analysis for the Evaluation of Estimated Glomerular Filtration Rate, Cholesterol and Triglycerides after Switching from Tenofovir/Emtricitabine Atazanavir/Ritonavir (ATV/r) to Abacavir/Lamivudine ATV/r in Patients with Preserved Renal Function

et al. 2016

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Background and Objectives:Renal toxicity due to tenofovir (TDF) has been largely described in patients with HIV infection. However, other antiretroviral drugs (such as atazanavir [ATV], especially when boosted by ritonavir, ATV/r) could perpetuate some degrees of renal impairment with or without TDF co-administration. Also, possible benefits of stopping TDF in patients without renal diseases is not well known. This study aimed at exploring evolution of renal function and lipid profile after switching from tenofovir/emtricitabine (TDF/FTC) to abacavir/lamivudine (ABC/3TC), maintaining the ATV/r component of the regimen.Methods:Patients in the Italian MASTER Cohort, who switched from TDF/FTC plus ATV/r to ABC/3TC plus ATV/r were included, provided that major renal diseases were not diagnosed before switching (i.e., baseline). Serum creatinine, estimated glomerular filtration rate (eGFR), total cholesterol, HDL and triglycerides were evaluated at baseline and at month 18 after switching.Results:126 patients were selected (80% males). Patients were mostly Italians (92%). 79% had undetectable HIV-RNA and 44% were co-infected by HBV and/or HCV. Median age at switch was 47 years (IQR 43-55). A small but significant decrease in serum creatinine [from 1.06 mg/dl (SD: 0.3) to 0.94 mg/dl (SD: 0.2); p<0.001] with an improvement in eGFR [from 86.8 ml/min (SD: 33) to 96.4 ml/min (SD: 37); p<0.001] were observed in per protocol analysis at month 18. Also ITT analysis showed a decrease in mean serum creatinine [from 1.08 mg/dl (SD: 0.35) to 0.95 mg/dl (SD: 0.24); p<0.001] with an improvement in mean eGFR [from 86.9 ml/min/1.73m2 (SD: 24.11) to 95.8 ml/min/1.73m2 (SD: 19.99); p<0.001]. Total cholesterol increased [from 188 mg/dl (SD: 42) to 206 mg/dl (SD: 44); p<0.001] but also HDL increased as well [from 46 mg/dl (SD: 14) to 54 mg/dl (SD: 19); p=0.015]. An increase in triglycerides concentration was observed [from 162 mg/dl (SD: 144) to 214 mg/dl (SD: 109); p=0.027] in per protocol analysis. Also ITT analysis showed increases of both total cholesterol [from 187 mg/dl (SD: 43.69) to 203 mg/dl (SD: 44.10); p<0.001] and HDL fraction [from 46 mg/dl (SD: 15.49) to 52 mg/dl (SD: 17.13); p=0.002] at month 18.Conclusion:This analysis reports an improvement in eGFR and an increase in total cholesterol and HDL fraction at month 18 after switching to ABC/3TC plus ATV/r. Given the fact that renal function was not significantly affected at baseline, our findings may suggest the utility of a proactive switch from TDF to ABC, when otherwise indicated, in patients who cannot avoid using a nucleoside backbone.

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“…One GIN case achieved complete resolution of renal function [ 2 ], whereas another showed partial improvement of renal function after steroid therapy [ 3 ]. Initiation of steroid therapy for GIN may have been too late in the case reported below, as compared with the three previous GIN patients who received steroids within 1 month of atazanavir withdrawal [ 2 – 4 ]. As is the case in a patient who was started on steroids after he developed AKI twice [ 5 ], this treatment delay might be associated with the incomplete recovery of renal function despite the almost complete cure of severe interstitial inflammation.…”

Section: Acute Interstitial Nephritis and Chronic Crystal-associated mentioning

confidence: 99%

“…[ 3 ] 60/M 2.3 4.1 GIN +/+ Partial remission with steroids after ATV cessation Kanzaki et al . [ 4 ] 50/M 2.18 5.2 GIN +/+ Unknown Coelho et al . [ 5 ] 71/M 7.1 2.8 GIN +/+ No remission with steroids after ATV cessation.…”

Section: Acute Interstitial Nephritis and Chronic Crystal-associated mentioning

confidence: 99%

Atazanavir nephrotoxicity

Hara

Suganuma

Yanagisawa

et al. 2015

Clinical Kidney Journal

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Atazanavir is commonly used as one of the key drugs in combination antiretroviral therapy for human immunodeficiency virus (HIV). However, atazanavir has the potential to yield its crystalline precipitation in urine and renal interstitial tissues, leading to crystalluria, urolithiasis, acute kidney injury (AKI) or chronic kidney disease (CKD). In epidemiological studies, atazanavir/ritonavir alone or in combination with tenofovir has been associated with increased risk of progression to CKD. However, renal biopsies were not provided in these studies. Case reports showing an association between atazanavir use and tubulointerstitial nephritis among HIV-infected individuals provide clues as to the potential causes of atazanavir nephrotoxicity. We now review atazanavir-related kidney disease including urolithiasis, renal dysfunction and interstitial nephritis and illustrate the review with a further case of atazanavir-associated kidney injury with sequential renal biopsies. There are two forms of atazanavir-associated tubulointerstitial nephritis: acute tubulointerstitial nephritis that may develop AKI rapidly (in weeks) after initiation of atazanavir, and chronic tubulointerstitial nephritis that may develop progressive CKD slowly (in years) with granuloma and intrarenal precipitation of atazanavir crystals as well as crystalluria. Caution should be exercised when prescribing atazanavir to patients at high risk of CKD, and therapy should be reevaluated if renal function deteriorates, especially associated with crystalluria and hematuria.

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Diffuse Tubulointerstitial Nephritis Accompanied by Renal Crystal Formation in an HIV-infected Patient Undergoing Highly Active Antiretroviral Therapy

Cited by 17 publications

References 25 publications

Clinical Pharmacology in HIV Therapy

Clinical Pharmacology in HIV Therapy

Exploratory Analysis for the Evaluation of Estimated Glomerular Filtration Rate, Cholesterol and Triglycerides after Switching from Tenofovir/Emtricitabine Atazanavir/Ritonavir (ATV/r) to Abacavir/Lamivudine ATV/r in Patients with Preserved Renal Function

Atazanavir nephrotoxicity

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