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Table 1 Case reports of acute kidney injury associated with tenofovir alafenamide use

From: Tenofovir alafenamide nephrotoxicity: a case report and literature review

Clinical feature

Novick TK et al. 2017 [9]

Serota DP et al. 2018 [8]

Alvarez H et al. 2018 [7]

Bahr NC et al. 2019 [6]

Heron JE et al. 2020 [5]

The present case

Age (years)

58

70

51

54

46

49

Sex

Male

Male

Male

Male

N/A

Female

Ethnic

African American

N/A

Caucasian

N/A

N/A

Asian

Co-infection

HCV

HCV

None

None

HCV

None

Co-morbidities

Cirrhosis

Diabetes

Drug abuse

Cirrhosis

Alcohol use

None

Dyslipidemia

Hypothyroidism

Hodgkin lymphoma

Hypertension

Dyslipidemia

IgA nephropathy

Viral load (copies/mL)

14,000

 > 1 million

38

suppressed

N/A

 < 50

CD4 (cells/µL)

367

100

587

N/A

N/A

1,096

TDF exposure

2 years

None

6 years

10 years

Yes

4 years

Baseline Cr (mg/dL)

0.9

1.2

N/A

0.59

N/A

1.05

Baseline CrCl

N/A

50 mL/min

N/A

N/A

N/A

63.5 mL/min/1.73m2

Baseline proteinuria

UPCI 0.27 g/gCr

N/A

N/A

N/A

N/A

Protein 2 + 

Regimen

TAF/FTC + DRV/c

EVG/c/FTC/TAF

EVG/c/FTC/TAF (intentional overdose)

TAF/FTC + DRV/r + RAL

TAF + FTC + DRV/c

TAF/FTC/DTG

Significant concurrent medications

None

Sofosbuvir

Ledipasvir

None

None

Carboplatin

Gentamicin

None

Duration of TAF prior to presentation

2 months

3 months

9 months

2 months

N/A

3 months

Presentation

Oliguric acute kidney injury with volume overload

Acute kidney injury with hyperkalemia and non-anion gap metabolic acidosis

Acute kidney injury

Fanconi syndrome

Renal proximal tubulopathy (hypophosphatemia, hypokalemia, glucosuria, and proteinuria)

Acute kidney injury with proteinuria and hematuria

Cr at diagnosis (mg/dL)

4.0

5.2

2.15

5.56

0.76

2.30

Proteinuria

24-h urine protein 8.5 g/day

24-h urine protein 6.3 g/day

No proteinuria

N/A

UPCI 1.36 g/g

Protein 3 + 

Urine sediments (cells/HPF)

RBC 5

WBC 1

RBC 3

WBC 2

N/A

N/A

N/A

RBC 5–10

WBC 3–5

Kidney biopsy

Diabetic nephropathy, focal glomerular hypercellularity, immune complex deposition, and mitochondrial injury

Not done

Not done

Not done

Not done

IgA nephropathy, and acute tubular injury with megamitochondria

Treatment

Acute dialysis,

TAF-containing regimen was stopped

TAF-containing regimen and ledipasvir were stopped

TAF-containing regimen was stopped

TAF-containing regimen was stopped

Gentamicin was stopped

TAF-containing regimen was stopped

Outcome

Recovery (4 weeks after discharge, Cr was 0.9 mg/dL)

Recovery (12 weeks after discharge, Cr was 1.32 mg/dL)

Recovery (Cr returned to baseline level after 2 weeks)

Recovery (3 months after discharge, Cr was 1.11 mg/dL)

Recovery of tubulopathy

Improvement of Cr (2 months after TAF was discontinued, Cr was 1.82 mg/dL)

Possible explanations

TAF and comorbidities

Drug-drug interaction between Ledipasvir, cobicistat, and TAF

Drug overdose of cobicistat and TAF

TAF

Sepsis and lymphopenia leading to TAF and gentamicin toxicities

TAF and comorbidities

  1. DRV/c: Darunavir/Cobicistat; DRV/r: Darunavir/Ritonavir; EVG/c/FTC/TAF: Elvitegravir/Cobicistat/Emtricitabine/Tenofovir alafenamide; RAL: Raltegravir; UPCI: Urine protein creatinine index