Reference values for serum creatinineReference values for serum creatinineconcentrations with Jaffe-compensated

assay in Iranian adult subjectsassay in Iranian adult subjects

Asghar Ghasemi Iraj Azimzadeh Saleh Zahediasl Fereidoun AziziAsghar Ghasemi, Iraj Azimzadeh, Saleh Zahediasl, Fereidoun Azizi

Endocrine Physiology Research Center, Research Institute forEndocrine Sciences, Shahid Beheshti University of MedicalSciences,Tehran, Iran

IntroductionChronic kidney disease is a worldwide public health problem with

increasing prevalence and incidenceg p

Glomerular filtration rate (GFR), the best overall index of renal

function, is mostly estimated from serum creatinine concentration

Any equation using serum creatinine level for estimating GFR is

dependent on the serum creatinine assayp yLevey AS: Ann Intern Med 139:137-147, 2003------------- Hosseinpanah F: BMC Public Health 9:44, 2009Levey AS: Ann Intern Med 130:461-470, 1999--------------- Selvin E: Am J Kidney Dis 50:918-926, 2007

Coresh J: Am J Kidney Dis 39:920-929, 2002--------------- Hetu PO: Clin Biochem 43:1158-1162, 2010yKuster N: Clin Biochem 45:320-325, 2012--------

Dr. Ghasemi3

IntroductionSerum creatinine concentration is affected by factors other than creatinine filtration

including:including:

Sex

Age

Race

Diet

Muscle mass

Analytical methodLevey AS: Ann Intern Med 130:461-470, 1999 Ceriotti F: Clin Chem 54:559-566 2008Ceriotti F: Clin Chem 54:559-566, 2008Myers GL: Clin Chem 52:5-18, 2006

Dr. Ghasemi4

IntroductionJaffe method, used in most routine laboratories, has a low specificity and

overestimates serum creatinine by approximately 20-30% at physiological

values, because of noncreatinine chromogens (mainly proteins)g ( y p )

Enzymatic creatinine methods are more specific and have been widely

adopted for routine clinical laboratory as alternatives to the alkaline picrate

h dmethods

Coresh J: Am J Kidney Dis 39:920-929, 2002ChromyV: Clin Chem Lab Med 46:1127-1133 2008ChromyV: Clin Chem Lab Med 46:1127-1133, 2008JungeW: Clin Chim Acta 344:137-148, 2004

Dr. Ghasemi5

IntroductionFor serum creatinine, like other naturally occurring biochemical compounds, a

reference interval needs to be provided

Reports of reference intervals for serum creatinine levels in Asian populations,

considering IFCC (International Federation of Clinical Chemistry) criteria with

accurate description of the measurement method, are scant

To our knowledge, there is no documented report on reference values of serum

creatinine in Irancreatinine in Iran

Ceriotti F: Clin Chem 54:559-566, 2008--------- Jorgensen LG: Clin Chem Lab Med 42:817-823, 2004

Dr. Ghasemi6

AimAimTo determine age and sex specific reference intervalsTo determine age- and sex-specific reference intervals

for serum creatinine concentration using data from a g

population-based study from Iran

Dr. Ghasemi7

Subjects and Methods

Subjects

Participants of Tehran Lipid and Glucose Study (TLGS) from June Participants of Tehran Lipid and Glucose Study (TLGS) from June

2008 to September 2011

Number of subjects

5247 apparently healthy participants (2792 men and 2455 women), 5247 apparently healthy participants (2792 men and 2455 women),

aged 20 to 88 years

Separate analysis was done for healthy menopausal women (n= 452;

age range 51-84 years). g g y

Dr. Ghasemi8

Subjects and MethodsExclusion criteria

Pregnancy

Hypertension

Diabetes

History of cardiovascular disease, cancer, and diarrhea

History of hospitalization during the past 3 months

History of significant weight loss during past 6 months

Using medications including steroids, diuretics, betablockers, digitals, calcium channelg g , , , g ,

blockers, angiotensin converting enzyme inhibitors, aspirin and other anticoagulants,

lipid lowering drugs, male or female hormones, contraceptives (oral or injection), or

drugs for thyroid disordersDr. Ghasemi9

Subjects and MethodsCreatinine measurement

Serum creatinine was measured using the photometric Jaffe methodSerum creatinine was measured using the photometric Jaffe method

(Pars Azmoon Kit,Tehran, Iran)

In 382 samples, creatinine measurement was done with both Jaffe

and enzymatic p-aminophenazone (PAP) methodsy p p ( )

Method for determining reference values:

IFCC criteria (non-parametric method)( p )

Dr. Ghasemi10

R lResults

Dr. Ghasemi11

Regression line between Cr measurement with Jaffe and PAP (enzymatic) methods

2 5

Jaffe Cr = 0.863 × PAP Cr + 0.44 mg/dL

r = 0 973 n= 383 p < 0 001)

2.0

2.5 r 0.973, n 383, p < 0.001)dL

)

1.0

1.5

e cr

eatin

ine

(mg/

d

0.5

Jaff

0.0 0.5 1.0 1.5 2.0 2.50.0

PAP creatinine (mg/dL)

Dr. Ghasemi12

Bland-Altman method comparison for comparingcreatinine measurements by Jaffe and PAP methods

0.5

creatinine measurements by Jaffe and PAP methods

0.4

Mean =0.32 ± 0.05

+2SD=0.42

0 2

0.3

ea 0 3 0 05

-2SD =0.22

P (m

g/dL

)

0.1

0.2

Jaffe

- PA

P

0.5 1.0 1.5 2.0 2.50.0

Mean of Jaffe and PAP creatinine (mg/dL)

-0.1Dr. Ghasemi13

Comparison of serum creatinine concentration according to sex and age*: significant difference with other groups

1.0 WomenMen

: significant difference with other groups†: significant difference compared to men

0.7

0.8

0.9*

* †

0.80

ol/L

)

0 4

0.5

0.6 *†

crea

tinin

e ( μ

m

0.2

0.3

0.4

Seru

m

20-2

9

30-3

9

40-5

0

> 50

20-2

9

30-3

9

40-5

0

> 50

en-to

tal

en-to

tal0.0

0.1

0.57

A ( ) Me

Wom

eAge groups (years)

Dr. Ghasemi14

Reference intervals for serum creatinine concentration (mg/dL) in healthy d l bj di d i h d J ff h dadult subjects according to age and sex using the compensated Jaffe method

Age (years) n 95% Reference intervals Men 20-29 856 0.53-1.00 30-39 633 0.53-1.00 40-50 701 0 53-1 110.53 1.11 >50 602 0.53-1.11 All 2792 0.53-1.11WomenWomen 20-29 972 0.31.77 30-39 818 0.42-0.77

40 50 665 40-50 665 0.42-0.77 >50 452 0.42-0.88 All 2455 0.42-0.77

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Di i Discussion

Dr. Ghasemi16

Serum creatinine reference values (mg/dL) in selected countries

Age Creatinine reference values MethodCountry year

Age

(years)

Creatinine reference values

(μmol/L)

Method

Males Females

S th A t li (Ad l id ) 2000 18 70 0 70 1 20 0 50 0 91 C t d J ffSouth Australia (Adelaide)  2000 18-70 0.70-1.20 0.50-0.91 Compensated Jaffe

Germany 2004 18-74 0.71-1.17 0.54-0.96 Compensated Jaffe

Nordic countries 2004 ≥18 0 70 1 20 0 63 1 00

Compensated Jaffe

(Denmark, Finland, Iceland,

Norway, and Sweden) 2004 ≥18 0.70-1.20 0.63-1.00

India 2006 20-60 0.80-1.30 0.60-1.00 Enzymatic

S i 2007 19 65 0 72 1 20 0 59 0 96 C t d J ffSpain 2007 19-65 0.72-1.20 0.59-0.96 Compensated Jaffe

Belgium 2008 20-70 0.63-1.17 0.48-0.93 Enzymatic

Italy 2010 18-79 0.65-1.17 0.45-1.00 Compensated Jaffe

China 2011 20-91 0.66-1.11 0.49-0.79 Enzymatic

Kenya 2012 18-50 0.63-1.12 0.54-0.96 ND

Iran Present 20-88 0.53-1.11 0.42-0.77 Compensated

Dr. Ghasemi17

Conclusion1. Reference intervals for serum creatinine concentration

according to compensated Jaffe method derived from aaccording to compensated Jaffe method, derived from a

population-based study in Iran, are 0.53-1.11 and 0.42-0.77

mg/dL in men and women respectively

2. Upper limits of serum creatinine reference values are lowerpp

than European countries and are close to the China and Kenya

3 h l ld b d f h di i d3. These values could be used for research, diagnostic and

therapeutic purposes

Dr. Ghasemi18

Thanks

Intra-assay CVs were 2.2% and 3.1% for Jaffe and PAP methody J

respectively (n=72).

Inter-assay CVs for normal creatinine concentration were 4.1%

and 6.1% for Jaffe and PAP method respectively and for high

creatinine concentration were 1.3% and 1.7% for Jaffe and

PAP method respectively (n=17)PAP method respectively (n=17).

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