What is the best approach to manage a 60-year-old HIV-positive patient with impaired renal function (e-GFR 40 ml/min), proteinuria (1g/24h), and chronic anatomic distortion on renal ultrasound, who has been on antiretroviral therapy (ART) for 30 years?

Management of HIV-Positive Patient with CKD Stage 3a and Proteinuria on Long-Term ART

This patient requires immediate nephrology referral for renal biopsy to determine the underlying cause of chronic kidney disease, optimization of antiretroviral therapy by switching from any nephrotoxic agents (particularly tenofovir disoproxil fumarate or ritonavir-boosted protease inhibitors) to safer alternatives like tenofovir alafenamide or integrase inhibitors, and initiation of ACE inhibitor therapy for proteinuria reduction. 1, 2

Immediate Diagnostic Workup

Nephrology referral for renal biopsy is warranted given the combination of significant proteinuria (1g/24h), chronic anatomic distortion on ultrasound, and progressive renal dysfunction (eGFR 40 mL/min). 1 The chronic anatomic changes suggest this is not simply acute drug toxicity but rather established structural kidney disease requiring histopathological diagnosis to guide therapy. 1

Key Differential Diagnoses to Consider:

• HIV-associated nephropathy (HIVAN): Although less common in the modern ART era, 30 years of HIV infection increases risk, and echogenic kidneys with anatomic distortion on ultrasound are characteristic findings. 1
• ART-induced nephrotoxicity: After 30 years of therapy, cumulative tenofovir or protease inhibitor exposure may have caused chronic tubular injury. 1, 2
• Immune complex glomerulonephritis: HIV-related or from co-infections (hepatitis B/C). 1
• Traditional CKD: Hypertension and diabetes are increasingly important in aging HIV populations. 1

Antiretroviral Therapy Optimization

Immediately review and modify the current ART regimen to eliminate nephrotoxic agents. 1, 2

If Currently on Tenofovir Disoproxil Fumarate (TDF):

• Switch to tenofovir alafenamide (TAF) as the first-line alternative, which provides significantly lower systemic tenofovir exposure and reduced nephrotoxicity risk. 2, 3
• Alternative: Switch to abacavir (after HLA-B*57:01 screening to prevent hypersensitivity reactions), which requires no dose adjustment for renal insufficiency. 1, 4
• Do NOT continue TDF in a patient with eGFR 40 mL/min and proteinuria when safer alternatives exist. 1, 2

If Currently on Ritonavir-Boosted Protease Inhibitors:

• Switch to unboosted integrase inhibitors (dolutegravir, bictegravir) or ritonavir-boosted darunavir if protease inhibitor is necessary. 1, 2
• Avoid atazanavir and lopinavir/ritonavir, which significantly increase nephrotoxicity risk, especially when combined with tenofovir. 1, 2

Dose Adjustments Required:

With eGFR 40 mL/min, multiple antiretrovirals require dose modification. 1 Consult www.hiv-druginteractions.org for specific dosing and drug-drug interactions. 1

Proteinuria Management

Initiate ACE inhibitor therapy immediately for the 1g/24h proteinuria, targeting a 50% reduction in proteinuria as evidence of therapeutic effect. 1, 4

• ACE inhibition has demonstrated improved renal survival in HIV-associated nephropathy, with one study showing median renal survival of 479 days in treated patients versus 146.5 days in untreated patients (all progressing to ESRD). 1
• Start with a low dose (e.g., enalapril 2.5-5 mg daily) and titrate based on blood pressure and potassium levels. 1
• Avoid calcium channel blockers due to potential dangerous interactions with protease inhibitors causing hypotension and conduction delays. 1, 4

Monitoring Strategy

Increase monitoring frequency to every 2-4 months given CKD stage 3a with proteinuria and ongoing ART modifications. 1

Essential Monitoring Parameters:

• Serum creatinine and eGFR using CKD-EPI equation (preferred over other formulas). 1
• Quantified proteinuria using spot urine protein-to-creatinine ratio. 1
• Urinalysis for glycosuria (suggests proximal tubular dysfunction from tenofovir), hematuria, and pyuria. 1, 2
• Serum phosphate if TDF exposure suspected, as hypophosphatemia with elevated fractional excretion indicates tubulopathy. 2, 5
• Hepatitis B and C serology if not previously done, as co-infection increases CKD progression risk 2-3 fold. 1

Important Caveat:

Be aware that certain antiretrovirals (dolutegravir, rilpivirine, cobicistat) can increase serum creatinine by 5-20 mL/min through inhibition of tubular creatinine secretion without true GFR decline. 1 This should be considered when interpreting eGFR changes after ART switches.

Additional Management Considerations

Aggressively control traditional CKD risk factors, as these become increasingly important with improved HIV survival. 1

• Target blood pressure <130/80 mmHg (lower if tolerated with ACE inhibitor). 1
• Screen for and manage diabetes mellitus. 1
• Avoid all nephrotoxic medications including NSAIDs, aminoglycosides, and contrast agents when possible. 1

Prepare for potential renal replacement therapy given CKD stage 3a with proteinuria and anatomic changes suggesting progressive disease. 1

• Early vascular access planning if hemodialysis anticipated (native arteriovenous fistula preferred). 1
• HIV-infected patients on HAART achieve dialysis survival rates comparable to HIV-negative patients. 1
• Kidney transplantation is available through clinical trials or routine care at specialized centers for appropriately selected HIV-positive patients. 1

Critical Pitfalls to Avoid

• Do not delay nephrology referral for biopsy in the setting of unexplained proteinuria with anatomic changes—histological diagnosis is essential for targeted therapy. 1
• Do not continue nephrotoxic ART "because the patient has been stable on it"—30 years of exposure may have caused cumulative damage that will progress without intervention. 1, 2
• Do not withhold ACE inhibitors due to concerns about hyperkalemia or acute GFR decline—the long-term renal protective benefits outweigh these manageable risks in proteinuric kidney disease. 1, 4
• Do not assume this is simply "aging kidneys"—the combination of HIV, long-term ART exposure, and potential co-infections requires systematic evaluation. 1, 6