What does a high estimated Glomerular Filtration Rate (eGFR) indicate in a patient with Behçet's disease on azathioprine and low-dose prednisone?

What Does a High eGFR Indicate?

A high eGFR typically indicates either increased kidney filtration (hyperfiltration) or measurement artifact, and in most clinical contexts, it does not represent kidney disease but rather reflects physiological states, body composition factors, or limitations of creatinine-based estimation equations. 1

Understanding High eGFR Values

Normal vs. Abnormal eGFR Ranges

• Normal eGFR is generally ≥60 mL/min/1.73 m², with values above this threshold not typically indicating kidney dysfunction 1
• The KDIGO guidelines emphasize that eGFR <60 mL/min/1.73 m² defines kidney insufficiency in young adults, but do not establish upper thresholds for pathology 1
• Age is a critical factor: eGFR physiologically decreases with aging, so interpretation must account for the patient's age 1

Clinical Significance of Elevated eGFR

High eGFR can indicate several distinct scenarios:

1. True Hyperfiltration (Increased Single-Nephron GFR)

• Associated with larger glomerular volume, larger kidney volume, male gender, higher body mass index, and higher 24-hour urine albumin 2
• May occur in early diabetes, obesity, or compensatory states after nephron loss 2
• Age-based thresholds for hyperfiltration: uncorrected mGFR >198 mL/min - 0.943×Age 2

2. Measurement Artifact from Low Muscle Mass

• Creatinine-based eGFR equations substantially overestimate GFR in patients with low muscle mass or sarcopenia 1
• This is particularly problematic in advanced CKD, elderly patients, and those with chronic illness 1, 3
• Serum creatinine generation varies with muscle mass, making eGFR both a marker of sarcopenia and kidney function 1

3. High Nephron Number

• Some individuals simply have more functioning nephrons, leading to higher total GFR without pathological hyperfiltration per nephron 2
• This represents normal variation rather than disease 2

Specific Context: Behçet's Disease on Azathioprine and Prednisone

In your specific clinical scenario, several factors are relevant:

Medication Effects on Kidney Function

• Azathioprine does not directly cause kidney damage or eGFR fluctuations 4, 5
• Azathioprine is well-tolerated in Behçet's disease, with hepatotoxicity being the primary concern (not nephrotoxicity) 5
• Low-dose prednisone similarly does not typically elevate eGFR 4, 5

Factors That Could Cause Apparent High eGFR in This Patient

Volume status changes are the most likely explanation:

• Dehydration or excessive diuresis can cause transient creatinine changes that affect eGFR calculation 6
• Hypotension can reduce renal perfusion, paradoxically affecting creatinine generation 6

Concomitant medications should be reviewed:

• NSAIDs, ACE inhibitors, or ARBs can cause creatinine fluctuations 6
• These are commonly used in Behçet's disease for inflammatory control

Normal physiologic variation:

• Creatinine varies based on muscle mass, diet, and hydration status 6
• A single high eGFR reading may simply reflect day-to-day variation 6

Clinical Approach and Monitoring

Immediate Assessment

Do not assume high eGFR represents kidney disease - instead, investigate alternative explanations:

• Review all medications for nephrotoxic agents 6
• Assess volume status and blood pressure 6
• Consider muscle mass and nutritional status 1, 3
• Repeat measurement to confirm the finding is persistent 6

When to Consider Alternative GFR Measurement

eGFR is inaccurate in settings of high, low, or rapidly changing GFR 3. Consider direct GFR measurement using iothalamate or iohexol clearance when:

• High-consequence medical decisions are required 7
• eGFR appears discordant with clinical presentation 1
• Precise kidney function assessment is needed for drug dosing 3

Ongoing Monitoring Recommendations

For patients on azathioprine and prednisone:

• Baseline and periodic renal function tests are recommended 6
• Monitor every 3-4 months during the first year, then every 6 months thereafter 6
• Use CKD-EPI equation for estimating eGFR in adults 6
• Consider cystatin C-based eGFR if creatinine-based estimates seem unreliable due to muscle mass issues 1, 7

Key Caveats

• eGFR has not been validated for drug dosing - continue using Cockcroft-Gault formula or other validated methods for medication adjustments 3
• eGFR is particularly inaccurate in older people, inpatients, differing racial groups, and obese individuals 3
• A high eGFR reading in isolation, without proteinuria or other markers of kidney damage, does not indicate kidney disease 1
• The decision to initiate dialysis should never be based on eGFR level alone, regardless of whether it is high or low 1