From the Guidelines
Yes, creatinine levels can be artificially elevated by certain substances and pathologies, independent of actual kidney dysfunction. Several medications can interfere with creatinine measurement, including cobicistat, dolutegravir, and trimethoprim, which inhibit tubular secretion of creatinine without affecting glomerular filtration, as noted in the study by 1. Certain substances like ascorbic acid (vitamin C), acetone, and glucose at high concentrations can interfere with laboratory assays that measure creatinine. Physiological conditions such as increased muscle mass, strenuous exercise, high-protein diets, and rhabdomyolysis can also raise creatinine levels due to increased creatine breakdown. Additionally, pathological states like diabetic ketoacidosis can falsely elevate readings through interference with colorimetric assays. When interpreting elevated creatinine results, healthcare providers should consider these potential confounders, especially when the elevation doesn't align with other clinical findings. In such cases, alternative markers of kidney function like cystatin C or direct GFR measurement may provide more accurate assessment of renal function, as suggested by the study 1, which recommends using the CKD-EPI equation for estimating eGFR in adults of any age, but also notes that equations based on cystatin C alone or in combination with creatinine may be more accurate in older people. Understanding these non-renal causes of creatinine elevation helps prevent unnecessary diagnostic procedures and inappropriate clinical decisions. Some key points to consider include:
- Medications that affect creatinine secretion, such as cobicistat and trimethoprim 1
- Physiological conditions that increase creatine breakdown, such as strenuous exercise and high-protein diets
- Pathological states that interfere with laboratory assays, such as diabetic ketoacidosis
- The use of alternative markers of kidney function, such as cystatin C or direct GFR measurement, to provide a more accurate assessment of renal function 1.
From the Research
Pathologies that Can Artificially Elevate Creatinine Levels
- Certain substances, such as trimethoprim, can inhibit the tubular secretion of creatinine, leading to a reversible increase in serum creatinine levels without affecting the glomerular filtration rate (GFR) 2, 3
- Trimethoprim-sulfamethoxazole (TMP-SMX) therapy has been associated with pseudo-elevation of serum creatinine levels, which can be distinguished from true nephrotoxicity by comparing creatinine-estimated and cystatin C-estimated GFRs 4
- Rhabdomyolysis, a rare but potentially life-threatening complication, can also lead to elevated creatinine levels, and has been reported in patients receiving TMP-SMX therapy 5, 6
Mechanisms of Artificial Elevation
- Trimethoprim inhibits the organic cation transporter 2 and multidrug and toxin extrusion protein 2-K in proximal tubules, leading to a reversible increase in serum creatinine levels 2
- TMP-SMX therapy can cause a dose-dependent increase in serum creatinine levels, which can be associated with hyponatremia and hyperkalemia 2
- Rhabdomyolysis can lead to the release of creatinine and other muscle enzymes into the bloodstream, resulting in elevated creatinine levels 5, 6
Clinical Implications
- Clinicians should be aware of the potential for pseudo-elevation of serum creatinine levels in patients receiving TMP-SMX therapy, and consider alternative methods for estimating GFR, such as cystatin C-estimated GFR 4
- Patients receiving TMP-SMX therapy should be monitored for signs of rhabdomyolysis, such as muscle pain and weakness, and for elevated creatinine kinase levels 5, 6
- The use of creatinine-based equations to estimate GFR may not be reliable in patients receiving trimethoprim, due to the inhibition of tubular creatinine secretion 3