A 33-year-old female with HIV and hepatitis B, HBV, is diagnosed with tenofovir nephrotoxicity. What is your next step?
The patient has had HIV for 3 years. She also has a history of hepatitis B virus, HBV. Her HIV is well controlled and her HIV medications include the TDF formulation of tenofovir.
She has a history of hypertension and CKD 3a. Her kidney function has worsened over the last few months. Her blood pressure is 122/81 on amlodipine and losartan. She is also taking empagliflozin.
Lab studies reveal glucose in the urine, but she is taking a SGLT2. Her blood tests show hypouricemia, hypophosphatemia, and a normal anion gap metabolic acidosis.
The empagliflozin is held, but the laboratory abnormalities remain.
Answer: Discontinue the TDF formulation of tenofovir, tenofovir disopril fumarate, and switch to the alternative formulation, TAF or tenofovir alafenamide.
The patient has Fanconi syndrome related to tenofovir nephrotoxicity.
It is expected that there will be an improvement in the patient’s kidney function and electrolytes after making this change.
Acute Kidney Injury and Tenofovir Nephrotoxicity in HIV Patients
Overview of Acute Kidney Injury (AKI)
Acute kidney injury (AKI) is a significant concern in patients with HIV infection. Using the TDF formulation of tenofovir has been associated with tenofovir nephrotoxicity. While chronic kidney disease is prevalent among HIV patients, effective antiretroviral therapy has shifted the focus from primary HIV nephropathy to other causes of kidney impairment.
Tenofovir and Its Side-Effects
Tenofovir, a nucleoside analogue, is known for its potential to cause tubular nephrotoxicity, which often presents as proteinuria. Patients on tenofovir regimens should have kidney function tests and urinalysis conducted biannually to monitor for any kidney issues.
Tenofovir nephrotoxicity can induce symptoms similar to Fanconi syndrome, including: * Glycosuria with normal plasma glucose levels * Mild proteinuria showing proximal tubular damage * Low serum bicarbonate levels without elevated anion gap, a non-anion gap metabolic acidosis * Phosphaturia leading to low serum phosphorus levels
Upon identifying tenofovir nephrotoxicity, that is tenofovir-related AKI, the primary treatment is to discontinue the drug. Some infectious disease specialists switch to the TAF formulation or a different HIV regimen. Once the patient has stabilized, SGLT2 inhibitors can be reintroduced.
Introduction of Tenofovir Alafenamide (TAF)
Tenofovir alafenamide (TAF), has transformed the management of HIV and hepatitis B virus (HBV). TAF is a more potent nucleotide transcriptase inhibitor with a different adverse effect profile, making it a preferred option in therapy.
Mechanism of Action of Tenofovir
Tenofovir is a nucleotide analog of adenosine 5′-monophosphate. In its parent form, it has limited membrane permeability and oral bioavailability. To enhance these properties, tenofovir is available as prodrugs, TDF and TAF.
Both TDF and TAF convert into their active form, tenofovir-diphosphate, which plays a crucial role in: * Inhibiting HIV replication by competing with deoxyadenosine 5′-triphosphate during DNA incorporation * Inhibiting HBV replication by targeting HBV polymerase
Nephrotoxicity of Tenofovir Disoproxil Fumarate (TDF)
TDF has been linked to new or worsening renal impairment, primarily because of damage to the proximal tubule caused by circulating tenofovir. The drug is eliminated renally through active tubular secretion and passive glomerular filtration. Renal damage occurs when there is an imbalance between plasma uptake and renal clearance, leading to tenofovir accumulation in the proximal tubule.
Severe manifestations of tenofovir nephrotoxicity can include: * Kidney failure * Fanconi syndrome
Risk factors for tenofovir nephrotoxicity in patients using TDF include: * Advanced HIV disease * Longer treatment duration * Low body weight, particularly in females * Preexisting renal impairment
Comparison of TDF and TAF
Unlike TDF, TAF does not require renal dose adjustments for patients with a creatinine clearance (CrCl) of 15 mL/min or greater. This characteristic allows TAF to be used in populations with some kidney impairment more effectively than TDF.
