CLINICAL CHEMISTRY DEPARTMENT 1 Creatinine is a breakdown

CLINICAL CHEMISTRY DEPARTMENT * 1

Creatinine is a break-down product of Creatine phosphate in muscle, and is usually produced at a constant rate by the body (depending on muscle mass). * 2

Creatine: main storage compound of high energy phosphate needed for muscle metabolism. Creatine Creatinine H 2 O Creatinine: anhydride of creatine! * 3

Creatinine is filtered out of the blood by the kidneys (glomerular filtration). There is little-to-no tubular reabsorption of creatinine. * 4

■ ■ * Men tend to have higher levels of creatinine because they generally have more skeletal muscle mass than women. Vegetarians have been shown to have lower creatinine levels. 5

Serum creatinine ■ ■ ■ Measuring serum creatinine is a simple test and it is the most commonly used indicator of renal function. A rise in blood creatinine level is observed only with marked damage to nephrons. Therefore, this test is not suitable for detecting early stage kidney disease. ■ * 6

■ ■ * A better estimation of kidney function is given by the creatinine clearance (Cr. Cl) test. A recent Japanese study suggests that a lower serum creatinine level is associated with an increased risk for the development of type 2 diabetes in Japanese men 7

Urine creatinine ■ ■ * Creatinine concentration in urine is also checked during creatinine clearance test. High creatinine levels indicate a pure test while low amounts of creatinine in the urine indicate a manipulated test, either through the addition of water in the sample or by drinking excessive amounts of water. 8

Principle of Clearance: - Some substances when filtered enter the tubules are not reabsorbed and so 100% excreted. Clearance Rate = GFR (inulin= gold standard for GFR Determination) * 9

- Some substances are filtered, enter tubules, and more of the substance is secreted enters the tubules. Clearance>GFR - Some substances are filtered, enter tubules, but are completely reabsorbed, so they did not reach the final urine (e. g. cystatin C) * 10

GFR: is the volume of plasma filtered (V) by the glomerulus per unit of time. GFR= V t * 11

GFR= US. VU P S. t ■ Creatinine clearance : is the volume of plasma from which creatinine is removed per unit of time. ■ Cr Cl =UCr x Vu ml/min. ( x 1. 73) PCr x t A * 12

Estimated GFR: ■ ■ * GFR (m. L/min) = (140 - Age) x Weight(kg) SCr(µmol/L)x 0. 81 (0. 85 if female)* 13

Analytic Methods For Creatinine ■ 1. 2. * Chemical methods: Jaffe method. Jaffe- Fixed Time (ά keto acids, cephalosporins) (bilirubin, hemoglobin). 14

Enzymatic Methods: 1. Creatininase – CK: Creatinine + H 2 O Creatininase Creatine + ATP CK creatine phosphate +ADP. ADP+ phosphoenolpyruvate PK pyruvae + ATP Pyruvate +NADH LD lactate + NAD ■ * 15

Creatininase - H 2 O 2: Creatinine + H 2 O Creatininase creatine Creatine + H 2 O creatinase sarcosine + urea Sarcosine +O 2 + H 2 O sarcosine oxidase glycine +CH 2 O +H 2 O 2 +4 AA +phenol peroxidase colored product. 2. * 16

Other methods: 1. 3, 5 - Dinitrobenzoic acid (DNBS) reagent strips, colored product unstable. 2. HPLC (reference method). ■ * 17

■ Specimen requirements. ■ Reference Value of serum Creatinine: Population * N. Range Female 0. 6 - 1. 1 mg/dl Male 0. 9 - 1. 3 mg/dl Child 0. 3 - 0. 7 mg/dl 18

Normal value of Urine Creatinine: ■ ■ * Female 600 - 1800 mg/day Male 800 - 2000 mg/day Reference range for creatinine clearance are: Male: 97 ml/min - 137 ml/min. Female: 88 ml/min - 128 ml/min. SIU = µmol/l 19

Cystatin C ■ ■ * Cystatin C or cystatin 3 (formerly gamma trace, post-gamma-globulin a protein, post -gamma-globulin a protein is mainly used as a biomarker, post-gamma-globulin a protein is mainly used as a biomarker of kidney function. Cystatin C can be measured in a random sample of serum using immunoassays such as Mutaz. I. Hassan 20

Thanks… * 21