What causes low creatinine levels?

Causes of Low Creatinine Levels

Low serum creatinine levels primarily result from reduced muscle mass, malnutrition, or inadequate dietary protein intake, requiring evaluation for protein-energy wasting and potential nutritional intervention to improve outcomes. 1

Primary Causes

• Reduced muscle mass conditions:

  • Advanced age and female sex 2
  • Muscle-wasting diseases 2
  • Amputation 2
  • Frailty in older adults 3

• Nutritional factors:

  • Low dietary protein (especially cooked meat) intake 2
  • Protein-energy malnutrition 2
  • Malnutrition and critical illness 2

• Laboratory interferences:

  • Jaffe assay interference (hyperbilirubinemia) 2
  • Enzymatic interference (hyperbilirubinemia, hemolysis) 2

Clinical Significance

• Low creatinine levels reflect decreased creatinine production from reduced skeletal muscle mass and/or inadequate dietary protein intake 2
• In dialysis patients with negligible renal function, low serum creatinine (<10 mg/dL) suggests decreased skeletal muscle mass and/or low dietary protein intake 2
• Low creatinine index correlates with mortality independently of cause of death 2
• Mortality risk increases at serum creatinine levels below 9-11 mg/dL in dialysis patients 2
• Lower creatinine muscle index is associated with frailty and increased mortality in older adults 3

Diagnostic Approach

• Calculate creatinine index to assess creatinine production, dietary skeletal muscle protein intake, and muscle mass 2
• Consider cystatin C measurement when low muscle mass is suspected, as it provides a more accurate assessment of GFR in patients with muscle wasting 1
• Evaluate for protein-energy malnutrition using additional markers such as serum albumin and prealbumin 1
• Measure both serum and urine creatinine to calculate creatinine clearance 1
• Low urinary creatinine is associated with smaller body dimensions and more severe heart failure in patients with new-onset/worsening heart failure 4

Management Strategies

For General Population

• Assess nutritional status and implement dietary interventions to increase protein intake if malnutrition is identified 1
• Monitor changes in creatinine levels over time, as declining values correlate with increased mortality risk 2
• Evaluate physical performance measures (gait speed, muscle strength) as lower creatinine clearance is associated with muscle atrophy and reduced walking speed 5

For Dialysis Patients

• Evaluate protein-energy nutritional status when predialysis serum creatinine is below approximately 10 mg/dL 2
• Monitor creatinine index with a goal of maintaining adequate muscle mass 2
• Recognize that in dialysis patients with negligible urinary creatinine clearance, the serum creatinine level will be proportional to skeletal muscle mass and dietary muscle intake 2

Special Considerations

• Creatine supplementation can artificially increase urinary creatinine concentrations 6
• Low urinary creatinine excretion is independently associated with increased risk of cardiovascular disease and all-cause mortality 7
• In heart failure patients, lower spot urinary creatinine is associated with an increased risk of weight loss and poorer exercise capacity/quality of life 4
• Small changes in creatinine may be within normal biological and analytical variability (14-17%) 8