Fatal lactic acidosis associated with tenofovir and abacavir

Giola, Massimo; Basilico, Cristina; Grossi, Paolo

doi:10.1016/j.ijid.2004.09.010

Cited by 19 publications

(16 citation statements)

References 10 publications

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“…5g). Our evidence pointing to glucose reprogram by TFV and ADV could be helpful to understand rare incidences of fatal lactic acidosis in patients during treatment with tenofovir41.…”

Section: Discussionmentioning

confidence: 83%

Tenofovir and adefovir down-regulate mitochondrial chaperone TRAP1 and succinate dehydrogenase subunit B to metabolically reprogram glucose metabolism and induce nephrotoxicity

Zhao

Sun

Lan

et al. 2017

Sci Rep

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Despite the therapeutic success of tenofovir (TFV) for treatment of HIV-1 infection, numerous cases of nephrotoxicity have been reported. Mitochondrial toxicity has been purported as the major target of TFV-associated renal tubulopathy but the underlying molecular mechanism remains unclear. In this report, we use metabolomics and proteomics with HK-2 cells and animal models to dissect the molecular pathways underlying nephropathy caused by TFV and its more toxic analog, adefovir (ADV). Proteomic analysis shows that mitochondrial chaperone TRAP1 and mtDNA replicating protein SSBP1 were significantly down-regulated in TFV and ADV treated HK-2 cells compared with controls. Transmission electron microscopy (TEM) revealed that TFV and ADV-treated HK-2 cells had accumulated glycogen, a phenotype that was also observed in mice treated with TFV and ADV. Analysis of the proteins in TCA cycle showed succinate dehydrogenase subunit B (SDHB) was nearly depleted in glucose oxidative phosphorylation pathway however certain enzymes in the glycolysis and glycogen synthesis pathway had elevated expression in TFV and ADV-treated HK-2 cells. These results suggest that TFV and ADV may cause mitochondrial dysfunction in renal tubular cells and reprogramming of glucose metabolism. The resulting glycogen accumulation may partially contribute to TFV and ADV induced renal dysfunction.

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“…5g). Our evidence pointing to glucose reprogram by TFV and ADV could be helpful to understand rare incidences of fatal lactic acidosis in patients during treatment with tenofovir41.…”

Section: Discussionmentioning

confidence: 83%

Tenofovir and adefovir down-regulate mitochondrial chaperone TRAP1 and succinate dehydrogenase subunit B to metabolically reprogram glucose metabolism and induce nephrotoxicity

Zhao

Sun

Lan

et al. 2017

Sci Rep

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“…A total of 4 fatal lactic acidosis cases caused by TDF are known, all of which were HIV-infected patients. [5–8] In all cases, the patients were coadministrated with other antiretroviral medication which could hamper mitochondrial function. Three cases coadministered didanosine and/or stavudine, [5–7] except the 1 which took TDF, abacavir, and nevirapine without didanosine regimen.…”

Section: Discussionmentioning

confidence: 99%

“…[4] A total of 4 previously known fatal lactic acidosis cases caused by TDF were all taking several antiviral agents at that time. [5–8] This is the first case of TDF-treatment-induced fatal lactic acidosis in CHB patient without HIV coinfection.…”

Section: Introductionmentioning

confidence: 99%

Fatal lactic acidosis in hepatitis B virus-associated decompensated cirrhosis treated with tenofovir

Jun

Lee

et al. 2017

Medicine

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Rationale:Recently tenofovir disoproxil fumarate (TDF) has been widely used as a first-line therapy for chronic hepatitis B (CHB) infection. Although TDF demonstrates successful viral suppression, the possibility of renal failure and lactic acidosis has been proposed with TDF administration, especially in human immunodeficiency virus co-infected patients. However, TDF induced lactic acidosis has never been reported in CHB mono-infected patients.Patient concerns:A 59-year-old man received TDF for hepatitis B associated with cirrhosis. After ten days of TDF administration, nausea, vomiting and abdominal pain developed. High anion gap acidosis with elevated lactate level (pH 7.341, pCO2 29.7 mmHg, HCO3- 15.6mmHg, lactate 3.2mmol/L, anion gap 15.4 mEq/L) was developed.Diagnosis:With no infection, normal diagnostic paracentesis, and urinalysis together with high anion gap and increased blood lactate levels suggested lactic acidosis.Interventions:TDF was stopped, and haemodialysis was performed to control lactic acidosis.Outcomes:Although stopping TDF instantly and treating lactic acidosis using hemodialysis, the patient died.Lessons:Although, Fatal lactic acidosis is very rare in TDF patient, however, decompensated cirrhotic patients should be closely observed to keep the possibility of lactic acidosis in mind.

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“…The literature data shows that lactic acidosis occurs most frequently in cancer patients, especially of the lymphatic system [7], acquired immunodeficiency syndrome treated with reverse transcriptase inhibitors (3.9/1000) [8][9][10][11], diabetes treated with metformin (2-9/100 000) [12][13][14][15]. The basic disorder of this syndrome is an excessive accumulation of lactic acid in the blood and the occurrence of lactic acidosis.…”

Section: Discussionmentioning

confidence: 99%

Lactic acidosis occurrence during exercises in the smoke chamber in a 53-year-old firefighter with no significant medical history

Bronisz¹,

Spychalska²,

Szafrańska³

2014

International Journal of Occupational Medicine and Environmental Health

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Lactic acidosis is a form of metabolic acidosis with a high anion gap, reduced rate of arterial blood pH under 7.35 mmol/l, and lactic acid concentration over 7 mmol/l. In the literature we can find some descriptions of the cases of lactic acidosis in patients with severe systemic diseases (cancer, acquired immunodeficiency syndrome, sepsis, diabetes with cardiovascular disease and after organ transplantations). We present the case of lactic acidosis in a patient with no chronic diseasea firefighter in whom lactic acidosis has developed during standard exercises in the smoke chamber.

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Fatal lactic acidosis associated with tenofovir and abacavir

Cited by 19 publications

References 10 publications

Tenofovir and adefovir down-regulate mitochondrial chaperone TRAP1 and succinate dehydrogenase subunit B to metabolically reprogram glucose metabolism and induce nephrotoxicity

Tenofovir and adefovir down-regulate mitochondrial chaperone TRAP1 and succinate dehydrogenase subunit B to metabolically reprogram glucose metabolism and induce nephrotoxicity

Fatal lactic acidosis in hepatitis B virus-associated decompensated cirrhosis treated with tenofovir

Lactic acidosis occurrence during exercises in the smoke chamber in a 53-year-old firefighter with no significant medical history

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