What factors can falsely lower Glomerular Filtration Rate (GFR)?

Factors That Can Falsely Lower GFR

Multiple factors can falsely lower glomerular filtration rate (GFR) measurements, including medications, clinical conditions, and physiological states that affect creatinine levels without actually reducing kidney function.

Medication-Related Factors

• Drugs that compete with creatinine for tubular secretion can cause falsely decreased GFR estimates by increasing serum creatinine without actually affecting kidney function 1
• Aminoglycoside antibiotics may spuriously elevate creatinine determinations when used concomitantly with cephalosporins, leading to falsely low GFR estimates 2
• ACE inhibitors and ARBs can cause an initial decrease in GFR (up to 30%) that reflects hemodynamic changes rather than worsening kidney disease 1
• Broad-spectrum antibiotics that decrease extrarenal elimination of creatinine can lead to falsely low GFR estimates 1

Patient-Related Factors

• Reduced muscle mass significantly affects creatinine-based GFR estimates, as lower creatinine generation leads to falsely low GFR when using standard equations 1
• Advanced age is associated with reduced muscle mass and may lead to inaccurate GFR estimates if not properly accounted for in estimation equations 1
• Malnutrition reduces creatinine generation and can falsely lower GFR estimates 1
• Muscle-wasting diseases reduce creatinine production, leading to inaccurate GFR estimates 1

Clinical Conditions

• Heart failure can affect non-GFR determinants of both serum creatinine and cystatin C, leading to inaccurate GFR estimates 1
• Cirrhosis alters non-GFR determinants of creatinine and may be associated with increased tubular creatinine secretion 1
• Catabolic states (including severe infections, inflammatory conditions, and high cell turnover as in some cancers) can affect creatinine and cystatin C levels 1
• Volume depletion/dehydration can cause pre-renal azotemia that temporarily reduces GFR without indicating intrinsic kidney damage 1

Laboratory and Technical Factors

• In vitro mixing of aminoglycosides with beta-lactam antibiotics in collected specimens can result in mutual inactivation, affecting laboratory measurements 2
• Delayed processing of blood samples can affect creatinine and cystatin C measurements 1
• Use of Jaffe method instead of enzymatic assays for creatinine measurement can introduce interference from many drugs and substances 1

Special Considerations

• For patients with factors that may falsely lower GFR estimates, consider using:

  • Combined creatinine-cystatin C based equations (eGFRcr-cys) which are more accurate when creatinine-based estimates alone are unreliable 1
  • Cystatin C-based estimates (eGFRcys) when the only abnormality is reduced muscle mass 1
  • Measured GFR (mGFR) using exogenous filtration markers when treatment decisions critically depend on accurate GFR assessment 1

• The KDIGO 2024 guidelines recommend using eGFRcr-cys in clinical situations when eGFRcr is less accurate and GFR affects clinical decision-making 1

Common Pitfalls and Caveats

• Relying solely on creatinine-based GFR estimates in patients with extreme body habitus (very low muscle mass or obesity) can lead to significant errors in GFR assessment 1, 3
• Failing to recognize that a 10-20% increase in serum creatinine after initiating ACE inhibitors or ARBs may reflect hemodynamic changes rather than kidney injury 1
• Not accounting for the wide inter-individual variability in the glucose-HbA1c relationship when interpreting GFR in patients with diabetes and kidney disease 1
• Overlooking that biological variability is inherent in both measured and estimated GFR, with mGFR actually showing larger time-to-time variability than eGFR in some studies 4

When GFR assessment is critical for clinical decision-making (such as medication dosing with narrow therapeutic windows or evaluation for kidney donation), measured GFR using exogenous filtration markers should be considered the gold standard approach 1.