Comparison of Estimated Glomerular Filtration Rate (egfr)

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1 Comparison of Estimated Glomerular Filtration Rate (egfr) among Three Common Formulas R. Mohammadi Biochemist i (DCLS, Ph.D.) Faculty member of Medical Faculty

2 Introduction Chronic kidney disease (CKD) is a significant public health problem. There is a progressive loss of renal function in CKD. Early identification (through laboratory screening) and management of these patients may delay the progression of renal disease.

3 Introduction Serum Urea and creatinine have moderate sensitivity and specificity for CKD Nonrenal conditions can lead in increase of serum urea and creatinine In contrast, serum and creatinine concentration may be in reference range during CKD stage 1 and probably stage 2

4 Introduction Measuring glomerular filtration rate (GFR) is widely accepted as the best overall index of kidney function and classification of CKD is on the basis of quantifying GFR. The most common method for assessing GFR is evaluation of creatinine clearance But Creatinine Clearance has limitations at four levels

5 Introduction Level 1: Tubular secretion Creatinine has about 5-10% tubular secretion By reducing GFR, creatinine secretion increases Organic compounds, such as salicylates, Cephalosporins, Cimetidine idi and Trimethoprim, compete with it secretion

6 Level 2 : Blood Levels Introduction Creatinine production has ±15% daily variation Diets and supplements may increase serum creatinine Muscle atrophy leads to decrease serum production

7 Introduction Level 3 : 24h Urine Collection Is cumbersome for patient Probability of Incomplete urine collection Patient hydration during urine collection Patient abstinence of tea, coffee, some drugs, and sever activity Preservation of urine

8 Introduction Level 4 : Analytical Problems Creatinine usually is measured by alkaline picrate method Hemolysis and icterus samples falsely reduce creatinine concentration Falsely increase may be due to ketones, glucose, fructose, protein, urea, ascorbate, and cephalosporins Method Standardization

9 Totally Introduction Day to day variation is about 15-20% So, decrease up to 20 ml/min in patient with normal renal function, may not be due to real GFR reduction

10 Introduction According to limitation of Creatinine Clearance, Using Estimated GFR (egfr) is recommended egfr Is Based on Serum Creatinine Measurement and Correction for Weight, Age, Sex, and probably Race, Body Surface Area (BSA), or Renal Disease Urine collection is not needed, so is more practical. But has some other limitations

11 Introduction More than 25 different formulas have been created to estimate GFR from plasma or serum level of creatinine. In this study we compared in Iran results of three common egfr equation. These include CG, MDRD, and CKD-EPI.

12 Method and Materials This is a retrospective study on a total 559 outpatients attending Masoud clinical laboratory between Jully and September (56%) patients were female and 246 (44%) were female. Patients less than 18 years old excluded from the study.

13 Method and Materials Venous blood was collected aseptically in vacutainer tube without anticoagulant and having gel seperator. After serum separation, serum creatinine was measured by kinetic alkaline picrate method using Kimipajouhan reagent and Roche calibrator lot on Hitachi 917 automated clinical chemistry analyzer. In every run we used Perci Norm and Perci Pat control materials.

14 Method and Materials patients were explained for collecting the 24 hours urine sample orally and by writing. Urine was collected in containers without any additive/preservative, but was demanded to maintain urine if 2-8 o C. Volume of 24 hours collected urine was measured in ml in volumetric flasks.

15 Method and Materials After through mixing of urine sample, 1:50 dilution was prepared with deionized water as diluent. The diluted urine samples were analyzed for creatinine by kinetic alkaline picrate method using Biosystem reagent and Roche calibrator lot on Hitachi 917 automated clinical chemistry analyzer. In every run we used Randox urine asy control 2 lot 566UC and Randox urine asy control 3 lot 571UC..

16 Method and Materials Height (H) was measured in centimeters and weight (W) was recorded in kilograms. Body surface area (BSA) was calculated according the following equation in m 2 : BSA = W x H x

17 Method and Materials

18 Method and Materials egfr : CG (Cockcroft-Gault Gault) equation Was Published in 1976 by Cockcroft and Gault Is Based on Serum Creatinine Measurment and Correction for Weight, Age, and Sex egfr = (140 age) x Weight 72 x Serum Creatinine Is Corrected for Female by multiplying 0.85

19 Material and Methods egfr : MDRD (Modification of Diet in Renal Disease) Equation Was Developed in 1999 by using patients who had CKD identified d by elevated serum creatinine i levels l Is Based on Serum Creatinine Measurment and Correction for Age, and Sex egfr = 186 x Serum Creatinine x age x F F Is for Female

20 Material and Methods egfr :CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Was Developed in 2009 by CKD- Epidemiology Collaboration group and intended to be more generalizable across various clinical settings than MDRD equation

21 Material and Methods egfr :CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) Male Gender Serum Creatinine i egfr = a x ( ) c x (0.933) age b Creatinine 80 μmol/l a 141 B 79.2 c Male > 80 μmol/l Female Female 62 μmol/l > 62 μmol/l Creatinine (µmol/l) = Creatinine (mg/dl dl) x 88.4

22 Results Population characteristics Variable Mean ± SD Range Age (year) ± Weight (kg) ± Height (cm) ± BSA (m 2 ) 1.84 ± Serum Creatinine (mg/dl) 1.17 ± Urine Creatinine (mg/dl) ± Urine Volume (ml/24h) 1715 ±

23 Results mgfr and egfr Variable ab Mean ± SD Range mgfr ± egfr : CG ± egfr : MDRD ± egfr : CKD-EPI ±

24 Results Linear regression - egfr : CG r = 0.66

25 Results Linear regression - egfr : MDRD r = 0.72

26 Results Linear regression - egfr : CKD-EPI r = 0.72

27 Results Bland-Altman Plot - egfr :CG

28 Results Bland-Altman Plot - egfr : MARD

29 Results Bland-Altman Plot - egfr : CKD-EPI

30 Discussion and Conclusion Study In Spain Was Made on 84 Nondialyzed Patients with CKD in the Stage 4 or 5 Mehod Creatinine Clearance Classic CG Corrected CG MDRD Results (ml/min/1.73m 2 ) 13.5 ± ± 5 12 ± ± 4.8 Correlation coefficient In corrected CG, 0.84 is used as correction factor to compensate for the effect of tubular secretion of creatinine and make it closer to glomerular filtration Classic CG equation is better than MDRD equation for estimating GFR in patients with advanced CKD

31 Discussion and Conclusion Study In China Was Made on 7832 General Population Mehod MDRD Equation CG Equation Results (ml/min/1.73m 2 ) 78.6 ± ± 21.6 MDRD mean was higher than CG mean This difference is higher in older

32 Discussion and Conclusion Study In Pakistan Was Made on 369 outpatients and inpatients Correlation coefficient with Correlation coefficient with Method creatinine clearance when creatinine clearance when serum creatinine<1.5 mg/dl serum creatinine>1.5 mg/dl CG Equation MDRD Equation

33 Limitations of egfr egfr Not a Perfect Test for Screening CKD, But IS Recommended. Is Not Suitable for GFR > 60 ml/min and < 15 ml/min Is Not Suitable for Children and Older Is Not Suitable for Vegetarians and Who Have Changed Body Mass Is affected by factors affecting on serum creatinine, creatinine excretion, and creatinine measurment

34

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