Creatinine: Uses, Effects, Side Effects, Dosage, Interactions, Risks

Creatinine (creatinine) is a metabolic product that is excreted in the urine (urinary). The laboratory parameter belongs to the renal retention parameters. It is used to assess the performance of the kidneys. An increase indicates impaired kidney function, as the substance is retained in the body (retention). Creatinine is formed in muscle tissue from creatine. Creatine itself is a substance in the muscles that serves to store energy. It is released again under stress and excreted renally as creatinine. Creatinine is glomerularly filtered and additionally tubularly secreted (creatinine-blind region).Creatinine is a marker for estimating the glomerular filtration efficiency (glomerular filtration rate, GFR) of the kidneys.It is determined by the Jaffé method, a color test in which a yellow-orange colored creatinine-picric acid complex is formed by the addition of picric acid.

The method

Material needed

  • Blood serum
  • 24h urine

Preparation of the patient

  • Not necessary

Interfering factors

False high creatinine concentration can be determined when taking the following drugs or substances or other conditions:

  • Ascorbic acid (vitamin C)
  • Bilirubin
  • Cephalosporins – these include mainly cefazolin, cefoxitin and cephalotin.
  • Ciclosporin (cyclosporin A)
  • Cimetidine
  • Cisplatin
  • Cobicistat
  • Cotrimoxazole
  • Eltrombopag
  • Fenofibrate
  • Flucytocin
  • Ketone bodies
  • Methoxyflurane (anesthetic)
  • Spironolactone
  • Triamterene, amiloride
  • Trimethoprim
  • Analgesics such as acetylsalicylic acid (ASA), fenoprofen, indomethacin or naproxen.
  • Muscular bone structure
  • High protein diet/meat consumption
  • Carbohydrates such as glucose and fructose

False-low creatinine concentrations may be due to the following situations and may underestimate the extent of renal dysfunction:

  • Low physical activity
  • Reduced muscle mass or cachexia (emaciation).
  • Malnutrition
  • Diabetes mellitus (due to hyperfiltration)
  • Cirrhosis of the liver
  • Pregnancy

Normal values in children – blood serum

Age Normal values in mg/dl Normal values in μmol/l
Newborn 0,66-1,09 58,34-93,70
1st month of life (LM) 0,5-1,2 44,2-106,08
1st-3rd year of life (LY) 0,4-0,7 35,36-61,88
4TH-6TH LY 0,5-0,8 44,2-70,72
7TH-9TH LY 0,6-0,9 53,04-79,56
10TH-12TH LY 0,6-1,0 53,04-88,40
13-15 LJ 0,6-1,2 53,04-106,08
16-18 LJ 0,8-1,4 70,72-123,76

Normal values in adults – blood serum

Gender Normal values in mg/dl Normal values in μmol/l
Female 0,66-1,09 58,34-93,70
Male, <50th LJ 0,84-1,25 74,25-110,50
Male, > 50th LY 0,81-1,44 71,60-127,30

Normal values – urine

Gender Normal values in g/24 h
Female 1,0-1,3
Male 1,5-2,5

Indications

As well as for therapy monitoring of the above diseases.

Interpretation

Interpretation of elevated valuesAcute renal failure (ANV)Prerenal.

Renal

  • Acute renal failure due to a wide variety of triggers such as medications or sepsis (blood poisoning).
  • Chronic renal failure – decreasing functionality of the kidneys.
  • EPH gestosis
  • Hemolysis
  • Myolysis
  • Plasmocytoma
  • Rapid progressive glomerulonephritis
  • Heavy metal intoxication
  • Sepsis

Postrenal

  • After a marathon run – increase in serum creatinine level by 1.5- to 2-fold or by 0.3 mg/dl; signs of tubular damage could also be detected; all patients recovered quite quickly from the damage
  • Obstruction of the urinary tract by stones, tumors, or the like
  • Opiates
  • Parasympatholytics

Chronic renal failure

  • Diabetic nephropathy (Kimmelstiel-Wilson syndrome).
  • Glomerulonephritides
  • Hypertension
  • Interstitial nephritides
  • Collagenoses
  • Plasmocytoma kidney (Ig light chain proteinuria).
  • Renovascular kidney disease
  • Cystic kidneys

Other causes

  • Muscle mass ↑
  • Acromegaly – increased growth of body end limbs due to increased growth hormone production.
  • Intensive muscular stress
  • See above “disruptive factors”

Interpretation of lowered values

  • Muscle atrophy (loss of muscle mass) or decreased muscle mass – children, cachectic patients, elderly patients (due to sarcopenia/age-associated excessive loss of muscle mass and muscle strength).
  • Pregnancy
  • Underweight

Other notes

  • Creatinine increases only when the glomerular filtration rate of the kidney (≈ functional capacity of the kidney) has already decreased by half!
  • Urine creatinine as a single examination has only a very low informative value; the same applies to serum creatinine, whose diagnostic sensitivity for the detection of chronic kidney disease (cN) is too low → better determination of creatinine clearance from the 24h collection urine.
  • In addition to serum creatinine using the MDRD formula* (Modification of Diet Renal Disease), calculation of glomerular filtration rate (GFR) from serum parameters (creatinine, urea and albumin) – taking into account age, sex, indication of black skin color – should be performed according to the European Guidelines; this allows earlier detection of chronic kidney disease.Caution! In normal subjects, the MDRD formula determines GFR too low; in cN, the result is acceptable in terms of compliance.
  • When determining impaired renal function (based on calculated GFR), direct measurement of GFR (creatinine clearance) is always required!
  • Creatinine determination is one of the most common laboratory determinations, but more and more cystatin C is used as a renal function marker. This parameter detects limitations earlier!
    • Cystatin C shows greater sensitivity (percentage of diseased patients in whom the disease is detected by use of the test, i.e., a positive test result occurs) and specificity (likelihood that actually healthy individuals who do not have the disease in question are also detected as healthy in the test) than serum creatinine in the range between 80-40 ml/min (GFR).
    • Cystatin C is furthermore more suitable than creatinine determination for the detection and risk classification of chronic kidney disease
  • Serum creatinine-based eGFR (estimated GFR, the estimated glomerular filtration rate) and urine-based albumin-creatinine ratio (ACR) are appropriate parameters for cardiovascular risk assessment (at least with respect to mortality and heart failure/heart failure), according to one study. The ACR was a stronger risk factor than smoking, hypertension (high blood pressure), and hyperlipidemia (dyslipidemia) across all risk populations, while eGFR had about equal predictive value.
  • Patients with apoplexy (stroke) with a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 but normal serum creatinine levels are independently at increased risk for a poor prognosis. Note: Renal function after apoplexy should therefore be determined using serum creatinine-based eGFR (estimated GFR; estimated glomerular filtration rate) rather than serum creatinine.
  • Azotemia (abnormal increase of nitrogenous end products of protein metabolism (residual nitrogen) in the blood): see urea below.

Notice. * The “Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) has redeveloped the MDRD formula, which contains the same four parameters, but weighted differently. The CKD-EPI formula results in a decrease in the prevalence (disease incidence) of renal failure (stage 3 to 5) from 8.7% to 6.3%.