When should a 43-year-old cisgender male on Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide) be referred to a nephrologist?

Nephrology Referral for a 43-Year-Old Male on Biktarvy

Refer this patient to a nephrologist if his eGFR is <30 mL/min/1.73 m², if he has continuously declining eGFR or rising albuminuria despite optimal management, or if there is uncertainty about the etiology of any kidney disease. 1, 2

Primary Indications for Nephrology Referral

eGFR-Based Criteria

• Refer when eGFR falls below 30 mL/min/1.73 m², as this represents stage 4 CKD and requires specialist co-management for preparation of potential renal replacement therapy 1, 2
• Refer if there is a rapid decline in eGFR (>5 mL/min/1.73 m² per year), which indicates progressive kidney disease requiring specialist evaluation 2
• Refer if there is an abrupt sustained decrease in eGFR >20% after excluding reversible causes such as volume depletion or medication effects 2

Albuminuria-Based Criteria

• Refer if albuminuria is ≥300 mg/g (or ≥1 g/day protein excretion) despite optimal blood pressure control and use of ACE inhibitors or ARBs 2, 3
• Refer if there are continuously increasing urinary albumin levels despite appropriate management 1, 2

Additional Clinical Triggers

• Resistant hypertension requiring 4 or more antihypertensive agents 2
• Persistent electrolyte abnormalities, particularly hyperkalemia or hypokalemia that is difficult to manage 2
• Uncertain etiology of kidney disease, including absence of expected diabetic retinopathy in a diabetic patient with kidney disease, heavy proteinuria, active urine sediment (red cell casts, >20 RBCs per high power field), or rapid onset of kidney dysfunction 1, 2

Biktarvy-Specific Considerations

Monitoring Requirements

• Monitor serum creatinine, estimated creatinine clearance, urine glucose, and urine protein prior to initiating Biktarvy and during treatment as clinically appropriate 4
• In patients with chronic kidney disease, also assess serum phosphorus regularly 4
• Biktarvy is not recommended in patients with severe renal impairment (CrCl 15 to <30 mL/min) or ESRD (CrCl <15 mL/min) 4

Tenofovir Alafenamide (TAF) Safety Profile

• While TAF has a more favorable renal safety profile than tenofovir disoproxil fumarate (TDF), postmarketing cases of renal impairment, acute renal failure, proximal renal tubulopathy, and Fanconi syndrome have been reported with TAF-containing products 4
• Discontinue Biktarvy if the patient develops clinically significant decreases in renal function or evidence of Fanconi syndrome 4
• Patients taking tenofovir prodrugs who have impaired renal function or are taking nephrotoxic agents (including NSAIDs) are at increased risk of renal adverse reactions 4

Timing and Urgency of Referral

Routine Referral (Non-Urgent)

• eGFR 30-44 mL/min/1.73 m² with stable kidney function 1, 2
• Albuminuria 30-299 mg/g with adequate blood pressure control 2

Prompt Referral (Within Weeks)

• eGFR <30 mL/min/1.73 m² 1, 2
• Rapidly declining eGFR (>5 mL/min/1.73 m² per year) 2
• Albuminuria ≥300 mg/g despite optimal management 2

Urgent Referral (Within Days)

• Acute kidney injury with features suggesting diagnoses other than prerenal azotemia or acute tubular necrosis 2
• Evidence of Fanconi syndrome or proximal renal tubulopathy 4
• Severe electrolyte disturbances 2

Common Pitfalls to Avoid

Underutilization of Albuminuria Testing

• Always assess albuminuria in addition to eGFR, as 59% of patients with CKD do not receive albuminuria testing, leading to missed opportunities for appropriate nephrology referral 5
• Patients without albuminuria testing have substantially lower odds of receiving guideline-recommended nephrology care (adjusted OR 0.47) 5

Late Referral

• Avoid referring only when dialysis is imminent (less than 1 year before renal replacement therapy), as late referral is associated with increased mortality and worse outcomes 2
• Early referral when eGFR is between 30-44 mL/min/1.73 m² allows for better preparation and optimization of management 1, 2

Medication Management Errors

• Do not discontinue ACE inhibitors or ARBs for mild to moderate increases in serum creatinine (<30%) in the absence of volume depletion 1, 2
• Adjust medication dosages appropriately for decreased kidney function, as many antiretrovirals and other medications require dose modification 2
• Avoid nephrotoxic agents such as NSAIDs in patients with any degree of kidney impairment 4, 3

Misattributing Kidney Disease

• In HIV-positive patients on antiretroviral therapy, do not automatically attribute kidney disease to HIV-associated nephropathy or medication toxicity without proper evaluation 2
• Consider non-HIV-related causes including diabetic kidney disease, hypertensive nephrosclerosis, and glomerulonephritis 1, 2

Benefits of Timely Referral

• Early nephrology consultation improves quality of care and delays dialysis when initiated at stage 4 CKD (eGFR <30 mL/min/1.73 m²) 1
• Specialist co-management enables coordinated care to slow CKD progression, optimize management of complications (anemia, secondary hyperparathyroidism, metabolic bone disease), and prepare for potential kidney replacement therapy 2, 3
• Multidisciplinary care including nephrology, dietary counseling, and education about renal replacement therapy options improves outcomes 2