Nephrology & Clinical Biochemistry
Créatinine et DFG | Clinique Omicron Québec
Serum creatinine and estimated glomerular filtration rate (eGFR) are the two reference biochemical markers for assessing renal function in routine clinical practice. Creatinine is a nitrogenous waste product produced in a continuous and relatively stable manner by the non-enzymatic degradation of muscle creatine and phosphocreatine - its production is therefore proportional to muscle mass and remains relatively constant in a given individual in the absence of sudden variations in muscle mass. It is freely filtered by the renal glomerulus, very little reabsorbed and slightly secreted by the proximal tubule (this tubular secretion, of around 10 to 15 % of excreted creatinine, increases as glomerular function declines - which tends to slightly overestimate residual renal function in advanced stages of renal failure). Serum creatinine is an imperfect marker of renal function when interpreted alone, as its concentration is highly dependent on physiological variables independent of glomerular filtration - principally muscle mass (age, sex, ethnicity, nutritional status, amputation, paralysis, muscle diseases) and diet (ingestion of cooked meat - cooking converts part of the muscle creatine into creatinine) - making it difficult to define a universal normal value and to detect early renal impairment in patients with low muscle mass (sarcopenic elderly, women, cachectic patients). Estimated glomerular filtration rate (eGFR), calculated by equations integrating serum creatinine, age, gender and sometimes race or cystatin C, is clearly more informative than creatinine alone for classifying the stage of chronic kidney disease (CKD) according to the KDIGO 2012 classification and for guiding therapeutic decisions (dosage adjustment of drugs, nephrotoxics, preparation for procedures with iodinated contrast media).
Reference values
| Population | Creatinine (µmol/L) | Remarks |
|---|---|---|
| Adult male (18-60 years) | 62 – 115 µmol/L | Higher values in men due to greater muscle mass |
| Adult woman (18–60 years) | 44 – 97 µmol/L | Values lower than those of humans – importance of comparing to sex and age |
| Elderly person (> 70 years old) | 50 – 100 µmol/L | Creatinine often low or normal despite reduced GFR — sarcopenia reduces creatinine production; «normal» creatinine in an elderly patient may mask moderate to severe CKD |
| Child (2–12 years) | 27 – 62 µmol/L | Progressively increasing values with muscle mass; specific pediatric formulas (Schwartz) to estimate GFR |
| Adolescent (12–18 years) | 44 – 88 µmol/L | Progressive augmentation towards adult values |
| Pregnant woman | 35 – 70 µmol/L | Physiological hemodilution and a 50% increase in GFR % during pregnancy → reduced creatinine; creatinine > 80 µmol/L during pregnancy warrants investigation |
GFR estimation equations
- CKD-EPI 2021 (Chronic Kidney Disease Epidemiology Collaboration): reference equation recommended by major scientific societies (KDIGO, Canadian Society of Nephrology) since 2021 — integrates serum creatinine, age, and sex; the 2021 version removed the «race» variable (previously, the 2009 version increased eGFR by 16 % for patients of African descent) to eliminate the introduction of racial bias in estimation; normal value in young adults: eGFR ≥ 90 mL/min/1.73 m²; accuracy: ±30 % in 85–90 % of cases for eGFR > 15 mL/min/1.73 m²
- CKD-EPI Creatinine-Cystatin C (2021): Combined creatinine + cystatin C equation—more accurate than creatinine alone (especially in subjects with extreme muscle mass—bodybuilders, cachectic, amputees, paralyzed); recommended when there is doubt about creatinine reliability; cystatin C is a marker of glomerular filtration independent of muscle mass but influenced by inflammation, hypothyroidism, corticosteroids, and smoking
- MDRD (Modification of Diet in Renal Disease): historical 4-variable equation (creatinine, age, sex, race) — less accurate than CKD-EPI for normal or subnormal GFR (tends to underestimate GFR at values > 60 mL/min/1.73 m²); still reported by some Quebec laboratories; replaced by CKD-EPI in current recommendations
- Creatinine clearance by 24-hour urine collection (Cockcroft method or direct measurement): less practical but more precise in certain contexts — pregnancy, extreme muscle mass, strict vegan diets, kidney transplant decisions; Cockcroft-Gault formula: [(140 – age) × weight (kg)] / [0.81 × creatinine (µmol/L)] × 0.85 (female) — still used for drug dosage adjustment of many medications in Canada
- Schwartz formula (pediatric): GFR (mL/min/1.73 m²) = k × height (cm) / creatinine (µmol/L); k = 36.5 for infants, 40 for children and girls, 49 for boys
KDIGO 2012 Classification of Chronic Kidney Disease Stages
Chronic kidney disease (CKD) is defined by the presence of structural or functional abnormalities of the kidney (including an eGFR < 60 mL/min/1.73 m²) with or without symptoms for more than 3 months. The KDIGO classification combines the G stage (eGFR) and the A stage (albuminuria) to define the renal prognosis.
| Stade G | DFGe (mL/min/1.73 m²) | Description and clinical implications | Follow-up frequency |
|---|---|---|---|
| G1 | Greater than or equal to 90 | Normal or increased kidney function — Possible CKD G1 if proteinuria or persistent structural abnormality (> 3 months) even with normal GFR | Annual |
| G2 | 60 – 89 | Slightly decreased — often asymptomatic; monitoring and control of risk factors (hypertension, diabetes, smoking) | Annual |
| G3a | 45 – 59 | Slightly to moderately decreased — early complications (hypertension, anemia, vitamin D deficiency, mild hyperphosphatemia); adjustment of certain nephrotoxic medications | At 6 months |
| G3b | 30 – 44 | Moderately to severely decreased — more frequent complications; renal anemia (EPO), secondary hyperparathyroidism, metabolic acidosis; avoid NSAIDs, lithium, aminoglycosides; IV iodine with caution | At 3–6 months |
| G4 | 15 – 29 | Severely compromised — preparation for dialysis or transplant; create vascular access (arteriovenous fistula); vaccinations (hepatitis B, flu, pneumococcus); phosphorus and potassium restriction | Monthly |
| G5 | Under 15 | End-stage renal disease (ESRD) — dialysis (hemodialysis or peritoneal dialysis) or kidney transplant necessary for survival; uremia, hyperkalemia, acidosis, pulmonary edema possible | Dialysis / transplant |
Causes of elevated creatinine and reduced GFR
- Pre-renal acute kidney injury (AKI) — the most frequent in hospitals: renal hypoperfusion due to reduced effective circulating volume — severe dehydration (gastroenteritis, vomiting, diarrhea, heat), hemorrhage, septic shock, decompensated heart failure (cardiorenal syndrome); creatinine rises in 24 to 48 hours and normalizes quickly with treatment of the cause; elevated urea/creatinine ratio (> 100 in SI units); concentrated urine (urinary Na < 20 mmol/L, fractional excretion of Na < 1 %)
- Intrinsic renal IRA: acute tubular necrosis (ATN) - ischemic (prolonged pre-renal IRA → tubular ischemia) or toxic (aminoglycosides, amphotericin B, cisplatin, iodinated contrast media, myoglobin - rhabdomyolysis, hemoglobin - hemolysis); acute interstitial nephritis (AIN) - drug-induced allergic reaction (penicillins, NSAIDs, PPIs, allopurinol) or infectious; rapidly progressive glomerulonephritis (RPGN) - nephrologic emergency; thrombotic microangiopathy (HUS, TTP)
- Post-renal (obstructive) AKI: urinary tract obstruction - bilateral ureteral stones or stones in a single kidney, severe prostate enlargement, prostate or bladder cancer, ureteral stricture, retroperitoneal fibrosis; relieving the obstruction rapidly normalizes creatinine if the obstruction is of short duration (< 48 to 72 hours)
- Chronic Kidney Disease — Principal Causes: Diabetic nephropathy (leading cause of CKD and ESRD in Canada - 40 % of new dialysis initiations); hypertensive nephrosclerosis (second leading cause); chronic glomerulonephritis (IgA, MPGN, FSGS); autosomal dominant polycystic kidney disease (ADPKD); hereditary nephropathies (Alport syndrome); lupus nephritis; analgesic nephropathy; aristolochic acid nephropathy (traditional remedies)
- Non-renal causes of elevated creatinine (false positives): increased muscle production—intense physical exercise, rhabdomyolysis, acromegaly, very high muscle mass (bodybuilder); significant intake of cooked meat or creatine supplements (transient); analytical interferences—chromogenic drugs (cefocitin, flucytosine) that are detected by the Jaffé method as creatinine; elevated bilirubin (interference negative—false decrease in creatinine with the Jaffé method)
- Causes of low creatinine (false negative of kidney function): severe sarcopenia (elderly, cachexia, muscular diseases, paraplegic, amputee); severe protein malnutrition; advanced liver cirrhosis (reduced creatinine synthesis by the liver - hepatic creatinine deficit); pregnancy; children
ℹ️
Serum creatinine does not rise measurably until about 50 % of kidney function is lost—it is therefore a late and insensitive marker for the early detection of early kidney damage. In an 80-year-old woman weighing 50 kg, a creatinine of 95 µmol/L (in the lab's «normal» range) corresponds to a CKD-EPI eGFR of about 45 mL/min/1.73 m²—a G3a stage of moderate CKD. The eGFR should always be calculated and interpreted in parallel with the creatinine.
Albuminuria — KDIGO classification, stage A
Albuminuria is an independent and complementary marker to eGFR for assessing renal and cardiovascular risk. It is measured by the urine albumin-to-creatinine ratio (UACR) on a morning urine sample.
| Stadium A | RAC (mg/mmol) or (mg/g) | Meaning |
|---|---|---|
| A1 | < 3 mg/mmol (< 30 mg/g) | Normal to slightly increased — low risk |
| A2 | 3 - 30 mg/mmol (30–300 mg/g) | Moderately increased (microalbuminuria) — early marker of diabetic nephropathy and endothelial damage; increased cardiovascular risk |
| A3 | 30 mg/mmol (> 300 mg/g) | Greatly increased (macroalbuminuria/proteinuria) — significant nephropathy; nephrotic syndrome if ACR > 300 mg/mmol; very high renal progression and cardiovascular risk |
Management and course of action according to stage
- Acute Kidney Injury (AKI) — emergencies and immediate measures: Pre-renal AKI → rapid IV fluid resuscitation (saline or Ringer's Lactate depending on the cause); immediate cessation of nephrotoxic medications (NSAIDs, aminoglycosides, contrast agents, ACE inhibitors/ARBs if functional AKI); obstructive AKI → emergency urinary drainage (bladder catheter if bladder obstruction, double-J stent or nephrostomy if ureteral obstruction); severe oligo-anuric AKI (eGFR < 15, life-threatening hyperkalemia, pulmonary edema, severe acidosis) → emergency dialysis
- MRC G1–G2 (eGFR ≥ 60) — prevention and monitoring: strict blood pressure control (target < 130/80 mmHg — ACE inhibitor or ARB if albuminuria; nephroprotective agents); optimal glycemic control in diabetes (target HbA1c < 7–7.5 %); SGLT2 inhibitors (dapagliflozin, empagliflozin, canagliflozin) — demonstrated reduction in renal progression regardless of initial eGFR in CREDENCE, DAPA-CKD, EMPA-KIDNEY trials; smoking cessation; sodium restriction (< 2 g/day of sodium); lipid profile and statins if high cardiovascular risk; annual albuminuria
- MRC G3 (eGFR 30–59) — complications and adjustments: screening and treatment of renal anemia (EPO — erythropoietin) if Hb < 100 g/L; secondary hyperparathyroidism — calcium, phosphorus, PTH, active vitamin D (calcitriol); metabolic acidosis — oral sodium bicarbonate if total CO₂ 24); medication dosage adjustments (metformin contraindicated if eGFR < 30, ACEI/ARB to monitor, antibiotics); avoid NSAIDs; referral to nephrology
- MRC G4-G5 (eGFR < 30) — preparation for renal replacement therapy: mandatory nephrology consultation; choice of RRT modality (hemodialysis, peritoneal dialysis, preemptive kidney transplant); creation of vascular access (arteriovenous fistula - AVF - ideally 6 months before anticipated dialysis); vaccinations (hepatitis B, influenza, pneumococcus, COVID-19); diet low in potassium, phosphorus, and sodium; correction of anemia, acidosis, and hyperparathyroidism; moderate protein restriction (0.6–0.8 g/kg/day) if not on dialysis
- Nephroprotective medications recommended in CKD with albuminuria: ACE inhibitors (ramipril, perindopril) or ARBs (telmisartan, irbesartan) — 30–40% reduction in renal progression and proteinuria %; SGLT2 inhibitors (dapagliflozin 10 mg/day — approved in Canada for CKD with eGFR 25–75 and ACR ≥ 22 mg/mmol); finerenone (nonsteroidal mineralocorticoid receptor antagonist) — reduction in renal progression in diabetic CKD (FIDELIO-DKD and FIGARO-DKD trials); semaglutide — reduction in renal risk in diabetes (FLOW trial 2024)
Critical values - urgent medical consultation or 911
Dial 911 or go immediately to the emergency room if creatinine is very highly elevated (often > 300–400 µmol/L in a few days) associated with oliguria or anuria, significant edema, dyspnea (fluid overload), arrhythmias (hyperkalemia), or altered consciousness (uremic encephalopathy). Consult a doctor without delay if creatinine rises by more than 26.5 µmol/L in 48 hours or more than 50 % in 7 days — diagnostic criteria for acute kidney injury according to the KDIGO classification — even in the absence of obvious symptoms.
For any routine kidney assessment, monitoring of known chronic kidney disease, screening in diabetic or hypertensive patients, or interpretation of abnormal creatinine, Clinique Omicron physicians conduct a comprehensive evaluation (creatinine, eGFR, ACR albuminuria, electrolyte panel, blood glucose) and ensure follow-up or referral to a nephrologist based on the stage. Consultations are available at our Quebec branches and via telemedicine. To book an appointment, visit cliniqueomicron.ca.
Consult at Clinique Omicron
Clinique Omicron provides screening and monitoring for chronic kidney disease in diabetic, hypertensive, or at-risk patients. They prescribe a complete workup (creatinine, eGFR CKD-EPI 2021, ACR, electrolytes, iron panel, PTH, Vitamin D), initiate appropriate nephroprotective treatments (ACEIs/ARBs, SGLT2 inhibitors), and refer to partner nephrologists for stages G3b and higher. Consultations are available at our Quebec branches as well as via telemedicine. To book an appointment, visit cliniqueomicron.ca.
The content of this page is provided for informational purposes only and does not substitute for the advice of a qualified healthcare professional. The interpretation of creatinine and eGFR should always be performed within the complete clinical context by a healthcare professional.
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