What are the next steps for an elderly male patient with impaired renal function (creatinine 1.41, GFR 56) and microhematuria on urinalysis (UA) while being treated with Truvada (emtricitabine/tenofovir disoproxil fumarate) for HIV?

Management of Elderly Male with Impaired Renal Function and Microhematuria on Truvada

Immediate Action Required

You must discontinue Truvada (tenofovir disoproxil fumarate/emtricitabine) immediately and switch to a renal-sparing antiretroviral regimen, while simultaneously investigating the microhematuria through nephrology referral. 1, 2

Discontinuation of Tenofovir Disoproxil Fumarate

• Tenofovir disoproxil fumarate (TDF) should be stopped when GFR decreases by >25% from baseline or drops below 60 mL/min/1.73m², which applies to this patient with GFR 56 1, 2

• The FDA explicitly states that TDF can cause renal tubular injury with severe hypophosphatemia (Fanconi syndrome) and acute renal failure, and recommends avoiding TDF with concurrent nephrotoxic agents 2

• Microhematuria in the setting of declining renal function on TDF is a red flag that may indicate proximal renal tubulopathy, which can manifest as persistent bone pain, fractures, or muscular weakness 2

Alternative Antiretroviral Selection

Switch to tenofovir alafenamide (TAF)-based regimen or abacavir-based regimen as these have significantly less renal toxicity:

• Tenofovir alafenamide is strongly preferred as it has minimal renal toxicity compared to TDF and can be used in patients with GFR >30 mL/min without dose adjustment 3, 4

• Abacavir (300 mg twice daily) is the only nucleoside analogue requiring no renal dose adjustment, but requires HLA-B*5701 screening before initiation to prevent hypersensitivity reactions 1, 3

• Integrase inhibitor-based regimens (dolutegravir, bictegravir, raltegravir) combined with TAF/emtricitabine or abacavir/lamivudine are recommended alternatives 5, 3

Nephrology Referral and Workup

Immediate nephrology referral is warranted for this patient based on multiple criteria:

• Patients with GFR <60 mL/min/1.73m² and proteinuria (or hematuria) should be referred to nephrology for additional evaluation including quantification of proteinuria, renal ultrasound, and potentially renal biopsy 5

• The combination of declining renal function, microhematuria, and TDF exposure requires investigation for:

  • TDF-induced proximal tubulopathy (check for glycosuria, hypophosphatemia, proteinuria) 2, 6
  • HIV-associated nephropathy (HIVAN) 5, 7
  • Immune complex glomerulonephritis 5, 7
  • Traditional causes of hematuria (malignancy, stones, infection) 5

Specific Diagnostic Testing

Order the following tests immediately:

• Quantify proteinuria using spot urine protein-to-creatinine ratio to determine extent of kidney damage 1, 7

• Check serum phosphate, urine glucose (for glycosuria), and urine protein to assess for Fanconi syndrome from TDF toxicity 2, 6

• Renal ultrasound to assess kidney size, structure, and rule out obstruction or masses 5, 1

• Urinalysis with microscopy to characterize the hematuria (dysmorphic RBCs suggest glomerular disease; normal RBCs suggest urological source) 5

• Consider urine cytology and cystoscopy if urological malignancy is suspected given patient's age and male gender 5

Blood Pressure Management

Initiate ACE inhibitor or angiotensin receptor blocker (ARB) therapy if proteinuria is confirmed:

• ACE inhibitors or ARBs should be used preferentially for HIV-infected patients with proteinuria, as they provide renoprotection and have been shown to improve outcomes in HIV-associated nephropathy 5, 1, 7

• Avoid calcium channel blockers if the patient requires protease inhibitors due to drug-drug interactions 5, 3

• Target blood pressure control aggressively, as hypertension accelerates CKD progression 5, 7

Monitoring Strategy

Increase monitoring frequency to every 2-4 months for patients with CKD stage 3a (GFR 45-59):

• Monitor serum creatinine, estimated GFR, quantified proteinuria, urinalysis, and serum phosphate 7

• Patients at increased risk for kidney injury (age >50 years, baseline GFR <90 mL/min, comorbidities like diabetes or hypertension) should be monitored every 3-6 months 5

• Track eGFR trajectories rather than single values, as progressive decline identifies individuals needing intervention 5

Critical Pitfalls to Avoid

Do not continue TDF in this clinical scenario - the combination of GFR 56, microhematuria, and elderly age represents multiple risk factors for progressive nephrotoxicity 2, 4, 8:

• Patients with mild renal dysfunction (GFR 60-89) have a 4.8-fold increased risk of nephrotoxicity on TDF, and those with moderate dysfunction (GFR 30-59) have a 15-fold increased risk 8

• Do not withhold antiretroviral therapy simply because of renal dysfunction severity - switch to appropriate renal-sparing regimen instead 5, 3

• Do not assume microhematuria is solely due to TDF - elderly males require thorough urological evaluation to exclude malignancy 5

• Do not use dose-adjusted TDF in this patient - switching to TAF or abacavir is superior to dose reduction 1, 3

Hepatitis B Considerations

If the patient has hepatitis B coinfection, special considerations apply:

• TAF is strongly preferred over TDF for dual HIV/HBV treatment given the renal impairment 3

• Entecavir can treat HBV but does not treat HIV, so is not appropriate as monotherapy 3

• Never discontinue TDF abruptly in HBV-coinfected patients without transitioning to another HBV-active agent, as this can cause severe hepatitis flares 2