Can Pre-Exposure Prophylaxis (PrEP) be prescribed to a patient with impaired renal function, as indicated by a Blood Urea Nitrogen (BUN)/creatinine ratio of 32?

Can PrEP Be Prescribed with a BUN/Creatinine Ratio of 32?

A BUN/creatinine ratio of 32 alone does not determine PrEP eligibility—you must calculate the creatinine clearance (CrCl), as TDF-based PrEP is contraindicated when CrCl falls below 60 mL/min/1.73 m² 1.

Critical Distinction: BUN/Cr Ratio vs. Creatinine Clearance

• The BUN/creatinine ratio of 32 is elevated (normal range 10-20), suggesting prerenal azotemia, dehydration, or increased protein catabolism, but this ratio does not directly assess glomerular filtration rate 1
• What matters for PrEP prescribing is the actual creatinine clearance calculation, not the BUN/Cr ratio 1
• You must calculate CrCl using the Cockcroft-Gault equation or measure eGFR before making any PrEP prescribing decision 1

Absolute Contraindication Threshold

TDF-based PrEP (tenofovir disoproxil fumarate/emtricitabine) is not recommended for persons with creatinine clearance below 60 mL/min/1.73 m² 1. This is an evidence rating AIIa recommendation from the International Antiviral Society-USA Panel 1.

Step-by-Step Decision Algorithm

Step 1: Calculate Baseline Creatinine Clearance

• Obtain serum creatinine and calculate CrCl using Cockcroft-Gault or eGFR 1
• Assess urine glucose and urine protein at baseline 2
• If the patient has chronic kidney disease, also measure serum phosphorus 2

Step 2: Apply the CrCl Threshold

• If CrCl ≥60 mL/min/1.73 m²: PrEP can be prescribed, but enhanced monitoring is required if CrCl is 60-89 mL/min 1
• If CrCl <60 mL/min/1.73 m²: TDF-based PrEP is contraindicated 1

Step 3: Identify High-Risk Features Requiring Enhanced Monitoring

Even if CrCl is ≥60 mL/min, certain patients require more frequent creatinine monitoring 1:

• Age >50 years: This group has substantially increased risk of renal impairment (hazard ratio 14.7) 3, 4
• Baseline eGFR <90 mL/min/1.73 m²: These patients have a 28.9-fold higher risk of developing renal impairment 3
• Concurrent nephrotoxic medications (NSAIDs, aminoglycosides) 2
• Hypertension or diabetes medications 1

Step 4: Determine Monitoring Frequency

• Standard monitoring: Creatinine measurement every 6 months for low-risk patients 1
• Enhanced monitoring: More frequent creatinine clearance monitoring (every 3 months or more) for patients >50 years, baseline eGFR <90 mL/min, or taking nephrotoxic agents 1

Alternative PrEP Options for Renal Dysfunction

If the patient has CrCl 60-89 mL/min or other renal risk factors:

• For men who have sex with men: Consider tenofovir alafenamide/emtricitabine (TAF/FTC) instead of TDF/FTC, as TAF has less impact on renal function 1, 5
• TAF-based regimens are preferred for MSM with or at risk for kidney dysfunction 5
• Note: TAF/emtricitabine is not currently recommended for PrEP in non-MSM populations per 2018 guidelines 1

Common Pitfalls to Avoid

Pitfall 1: Confusing BUN/Cr Ratio with Renal Function

• An elevated BUN/Cr ratio (32 in this case) may indicate prerenal azotemia from dehydration, not intrinsic renal disease 1
• Always calculate actual CrCl—the ratio alone cannot determine PrEP eligibility 1

Pitfall 2: Ignoring Age-Related Risk

• Patients aged 40-50 years experience mean CrCl declines of -4.2% on PrEP, and those >50 years decline by -4.9% 4
• Glomerular dysfunction occurs particularly in individuals older than 50 years 1
• Age >50 is an independent predictor requiring enhanced monitoring even if baseline CrCl is normal 1, 4

Pitfall 3: Missing Reversible Causes of Elevated BUN/Cr

Before attributing the elevated ratio to chronic kidney disease:

• Assess for dehydration, recent high-protein intake, or gastrointestinal bleeding 1
• Rule out prerenal causes that may normalize with hydration 1
• Recheck creatinine after addressing reversible factors 1

Clinical Context: Real-World Renal Safety Data

• In the large EPIC-NSW implementation study (6,808 participants), the rate of new-onset renal impairment (eGFR <60) was only 5.8 episodes per 1000 person-years 3
• Approximately 26% of PrEP users had baseline eGFR <90 mL/min, demonstrating that mild renal dysfunction is common and manageable with appropriate monitoring 3
• The iPrEx-OLE study showed mean CrCl decline of only -2.9% over 72 weeks, with dysfunction usually reversible upon discontinuation 1, 4
• Rechallenge with PrEP is often possible after transient renal dysfunction resolves 1

Hepatitis B Considerations

• Measure hepatitis B surface antigen (HBsAg) before PrEP initiation 1, 6
• If HBV-positive, TDF/emtricitabine regimens are preferred as they treat both HIV prevention and HBV 6
• Critical warning: Discontinuing TDF/emtricitabine in HBV-positive patients can cause severe acute hepatitis exacerbations or hepatic decompensation 1, 6, 2
• Close monitoring with clinical and laboratory follow-up for several months is required after stopping PrEP in HBV-positive patients 6, 2