Table 1.
Case reports of acute kidney injury associated with tenofovir alafenamide use
| 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 |
DRV/c: Darunavir/Cobicistat; DRV/r: Darunavir/Ritonavir; EVG/c/FTC/TAF: Elvitegravir/Cobicistat/Emtricitabine/Tenofovir alafenamide; RAL: Raltegravir; UPCI: Urine protein creatinine index