Summary
Creatinine is a waste product of muscle metabolism that is filtered almost entirely by the kidneys. When kidney function declines, creatinine accumulates in the blood. Serum creatinine — alongside eGFR (derived from creatinine) — is the standard test for detecting chronic kidney disease (CKD) and monitoring kidney health over time.
Creatinine is produced at a relatively constant rate from the breakdown of creatine phosphate in muscle, making its blood level a reliable marker of kidney filtration. Because creatinine is almost entirely excreted by glomerular filtration, any fall in glomerular filtration rate (GFR) causes creatinine to rise.
However, creatinine has an important limitation: serum levels depend on muscle mass. A muscular young man may have a creatinine of 110 μmol/L (normal for him) that would indicate significant kidney impairment in an elderly woman with low muscle mass. This is why eGFR — which corrects for age, sex, and ethnicity — is the preferred marker for assessing kidney function.
Creatinine should always be interpreted alongside eGFR, urea, and ideally urine albumin:creatinine ratio (ACR) for a complete kidney function assessment.
What It Is
Creatinine is a small, freely filtered, non-protein-bound molecule (MW 113 Da) produced from the non-enzymatic dehydration of creatine and phosphocreatine in skeletal muscle. Daily creatinine production is proportional to muscle mass and is remarkably constant in an individual from day to day.
The kidneys filter approximately 180 litres of blood per day through the glomeruli. Creatinine passes freely through the glomerular membrane and is not reabsorbed. A small additional amount is secreted by the proximal tubules. This makes creatinine clearance a close approximation of GFR.
When GFR falls — from any cause of kidney damage — creatinine rises. Because approximately 50% of kidney function must be lost before creatinine rises above the reference range, creatinine is an insensitive early marker of CKD — eGFR is more informative.
Reference ranges in UK adults: 45–90 μmol/L (women), 60–110 μmol/L (men).
Functions
Glomerular filtration rate (GFR) proxy
Creatinine is the most widely used surrogate for GFR — the gold standard measure of kidney filtration capacity.
CKD staging basis
eGFR derived from creatinine (and cystatin C) is used to stage chronic kidney disease and guide referral and treatment decisions.
Acute kidney injury (AKI) detector
A creatinine rise of > 26 μmol/L in 48 hours or > 50% in 7 days defines AKI — a medical emergency requiring urgent investigation.
Medication dosing guide
Many drugs are renally excreted — creatinine and eGFR guide dose adjustments for antibiotics, anticoagulants, and chemotherapy.
Reference Ranges
Serum Creatinine
Measured in μmol/L| Status | Range (μmol/L) | Range (mg/dL) | What it means |
|---|---|---|---|
| Low | < 45 (women) / < 60 (men) | Low creatinine — usually from low muscle mass. Rarely clinically significant but warrants context. | |
| Normal | 45–90 (women) / 60–110 (men) | Normal kidney filtration capacity. | |
| Elevated | > 90 (women) / > 110 (men) | Elevated — possible reduced kidney function. Calculate eGFR and investigate further. |
Reference ranges are sex-specific and vary by laboratory. Muscle mass strongly influences creatinine — interpret alongside eGFR. Creatinine is insensitive: ~50% of kidney function may be lost before it rises above the reference range.
Symptoms of Imbalance
Kidney disease is often asymptomatic until advanced — creatinine may be significantly elevated before symptoms appear.
- Low creatinine from low muscle mass is usually not symptomatic
- Muscle wasting conditions cause low creatinine (sarcopenia, myopathy)
- Often asymptomatic in early CKD
- Fatigue and weakness
- Swelling of ankles and legs (oedema)
- Foamy urine (from proteinuria)
- Hypertension
- Nausea and reduced appetite
- In advanced uraemia: itching, confusion, breathlessness
Causes of Imbalance
- Low muscle mass (sarcopenia, frailty, muscle-wasting conditions)
- Pregnancy (increased creatinine clearance lowers serum creatinine)
- Low protein diet
- Chronic kidney disease (CKD) — from diabetes, hypertension, or glomerulonephritis
- Acute kidney injury (AKI) — dehydration, NSAIDs, contrast media, sepsis
- High dietary meat intake (transient rise)
- High muscle mass (athletes — without kidney disease)
- Certain medications (trimethoprim, cimetidine — block tubular secretion without affecting GFR)
FAQs
Not necessarily. Creatinine has an important blind spot: approximately 50% of kidney function must be lost before creatinine rises above the laboratory reference range. This means someone can have significantly impaired kidneys — eGFR of 50–60 mL/min/1.73m² — with a creatinine that appears ‘normal.’ eGFR, urine albumin:creatinine ratio, and blood pressure together give a far more complete picture.
Yes. A large meat meal (particularly red meat or creatine supplements) can temporarily raise serum creatinine by 10–15% for several hours — enough to push a borderline result into abnormal territory. For accurate results, avoid large amounts of meat or creatine supplements for 24 hours before testing. A plant-based meal has negligible effect on creatinine.
Creatine is an amino acid derivative stored in muscles and used for rapid energy production (as phosphocreatine). Creatinine is the waste product formed when creatine breaks down — it is produced at a constant rate proportional to muscle mass and is filtered by the kidneys. Creatine supplements increase daily creatinine production and can raise serum creatinine without any kidney disease.
Yes — NSAIDs (ibuprofen, naproxen, diclofenac) reduce prostaglandin-mediated dilation of the afferent arteriole, decreasing glomerular perfusion and filtration. In people with pre-existing kidney disease, heart failure, dehydration, or who are taking ACE inhibitors/ARBs, NSAIDs can precipitate acute kidney injury with a significant creatinine rise. Regular NSAID use in CKD is strongly discouraged.
The NICE CKD guidelines recommend nephrology referral when eGFR 5 mL/min/year), unexplained haematuria with proteinuria, or difficult-to-control hypertension with CKD. In absolute creatinine terms, levels consistently > 150 μmol/L in women and > 200 μmol/L in men typically correspond to eGFR < 45 mL/min/1.73m² and warrant specialist review.
References
- National Kidney Foundation. KDOQI Clinical Practice Guidelines for Chronic Kidney Disease. Am J Kidney Dis. 2002;39(2 Suppl 1):S1–S266. View source
- Levey AS, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine. Ann Intern Med. 1999;130(6):461–470. View source
- NICE. Chronic kidney disease: assessment and management. NG203. 2021. View source