What can cause a high serum creatinine with normal blood urea nitrogen (BUN) and normal estimated glomerular filtration rate (eGFR)?

Elevated Creatinine with Normal BUN and eGFR

An isolated elevation in serum creatinine with normal BUN and normal eGFR most commonly results from medications that block tubular creatinine secretion (trimethoprim, cimetidine), increased creatinine production (high muscle mass, recent meat intake, rhabdomyolysis), or laboratory assay interference—none of which represent true kidney injury. 1

Medications That Block Tubular Secretion

The most frequent clinical scenario involves drugs that inhibit the proximal tubule's secretion of creatinine without affecting actual glomerular filtration:

• Trimethoprim blocks the organic cation transporter in the proximal tubule, raising serum creatinine by 10-20% within 2-3 days without reducing true GFR 1
• Cimetidine similarly inhibits tubular creatinine secretion, causing a reversible creatinine elevation 1
• Salicylates at high doses can block tubular secretion pathways 1

These medications create a discordance where creatinine rises but BUN remains normal because BUN is not secreted by the same tubular pathway. The eGFR calculation may show a mild decrease, but this is artifactual—the actual filtration rate is unchanged 1, 2.

Increased Creatinine Production

Creatinine generation can increase acutely or chronically, elevating serum levels without kidney dysfunction:

• Recent meat consumption (especially cooked red meat high in creatine) can raise creatinine by 0.2-0.5 mg/dL within hours 3
• High muscle mass in athletes or bodybuilders produces chronically elevated baseline creatinine 3
• Rhabdomyolysis causes massive creatinine release from damaged muscle, with creatinine rising disproportionately to BUN 3
• Corticosteroids and vitamin D metabolites may increase creatinine production and release rates 1

In these scenarios, BUN remains normal because urea production is not similarly affected, and the eGFR calculation may appear falsely low despite normal kidney function 4.

Laboratory Assay Interference

Certain substances interfere with creatinine measurement methods:

• Jaffe assay interference from hyperbilirubinemia can falsely elevate creatinine readings 3
• Enzymatic assay interference from hemolysis or severe hyperbilirubinemia affects newer enzymatic methods 3
• Ketoacidosis (particularly diabetic ketoacidosis) can cause assay interference 3

These interferences are more pronounced at normal creatinine ranges and should be suspected when clinical context doesn't match laboratory values 3.

Hemodynamic Effects of ACE Inhibitors/ARBs

While typically causing modest elevations in both creatinine and BUN, ACE inhibitors and ARBs can occasionally produce isolated creatinine rises:

• Acceptable creatinine increases up to 30% from baseline occur through reduced intraglomerular pressure and do not require drug discontinuation in the absence of volume depletion 3, 5
• These hemodynamic changes reflect altered renal blood flow rather than true kidney injury 3
• Discontinuation should only be considered when creatinine rises exceed 30% or hyperkalemia develops 5

The American Diabetes Association emphasizes that serum creatinine and potassium should be monitored periodically when using these agents 3.

Critical Distinction: True vs. False Elevation

The key clinical pitfall is mistaking a false creatinine elevation for acute kidney injury and unnecessarily discontinuing beneficial medications or pursuing invasive workup. 2

To distinguish false from true elevation:

• Check medication list for trimethoprim, cimetidine, or recent initiation of ACE inhibitors/ARBs 5, 1
• Assess dietary history for recent high-protein or meat-heavy meals 3
• Evaluate muscle mass and recent exercise—intense exercise within 24 hours can elevate creatinine 3
• Review laboratory method—confirm no hemolysis, icterus, or delayed sample separation 3
• Calculate BUN/creatinine ratio—a normal ratio (10-20:1) with isolated creatinine elevation suggests non-renal causes 6

When eGFR Appears Reduced Despite Normal Kidney Function

Serum creatinine alone is unreliable for assessing kidney function and can appear normal even when GFR has decreased by 40% 5, 4. Conversely, eGFR calculations based on falsely elevated creatinine will underestimate true kidney function 7.

If the clinical picture doesn't match the laboratory values—particularly if BUN is normal, urine output is preserved, and there are no other signs of kidney injury—consider the causes above before diagnosing kidney disease. 2

The American Diabetes Association recommends that uncertainty about the etiology of kidney disease warrants prompt nephrology referral 3, but in cases of clear medication effect or dietary influence, simply repeating measurements after addressing the reversible cause is appropriate 5.