1. ... Assessing renal function in the elderly The development of a new Iohexol based method to measure the true Glomerular Filtration Rate Gijs Van Pottelbergh, (MD, PhD) Belgium Promotor: Prof. Dr. Jean Marie Degryse (KULeuven en UCL) Co-Promotor: Prof. Dr. Pierre Wallemacq (UCL) 1

2. 1. Introduction: The renal function 2

3. Estimating the renal function in older persons: recent evolutions 2008 IDMS MDRD equation eGFR = 175 x (S cr ) -1.154 x (Age) -0.203 x (0.742 if female) x (1.212 if black) 2009 CKD-EPIcreat eGFR = 141 x min (S cr /k,1) a x max (S cr /k,1 )-1,209 x 0,993 Age x (1,018 if female) x (1,159 if black) 2012 CKD-EPIcreatcyst eGFR = 135 x min(Scr/k, 1) -a x max(Scr/k, 1) -0.601 x min(Scys/0.8, 1) - 0.375 x max(Scys/0.8, 1) -0.711 x 0.995 age [ x 0.969 if female ] [ x 1.08 if black ] 2012Berlin Initiative study: eGFR=767 x Scys -0.61 x Scr -0.40 x age -0.57 [ x 0.82 if female ] 3

4. Chronic kidney disease StageDescription GFR in ml/min/1.73m² 1 Normal GFR with signs of kidney damage* >90 + kidney damage* 2 Mild reduction in GFR with signs of kidney damage* 60-90 + kidney damage* 3Moderate reduction in GFR30-60 4Severe reduction in GFR CKD15-30 5Kidney failure<15 Table 2: CKD classification *kidney damage = persisting proteinuria, hematuria or structural abnormalities of the kidneys 4

5. CKD in Flanders (MDRD) 5

6. CKD in Russia (Crystal Data) 6

7. Problems with eGFR estimations in older people Serum creatininine depends on muscle mass -Age, gender and race -Chronic disease -Fysical activity -Medication use Large variation in muscle mass and physical activity in the (very) elderly 7

8. Main research question How to estimate or measure the renal function in (very) elderly? Final goal: validated method to measure or estimate the renal function in elderly 8

9. Differences between eGFR estimations (BELFRAIL n=544) Total matches Match <30 ml/min Difference <10% Difference 10–20% Difference 20–30% Difference >30% CG-MDRD277 (51.7%)27/60 (45%)9.9%22.8%27.2%40.1% MDRD-CKDEPI517 (96.5%)31/38 (82%)52.1%39.3%6.5%2.0% MDRD–CystC371 (69.2%)21/42 (50%)22.9%25.4%18.2%21.9% CystC–CG267 (49.8%)23/60 (38%)22.9%21.8%17.7%37.5% CystC–CKDEPI369 (68.8%)23/47 (49%)31.7%28.9%18.7%20.6% CKDEPI–CG294 (54.8%)33/57 (58%)32.6%29.9%26.3%11.2% 9

10. GFR Iohexol as reference standard 10

11. GFR Iohexol as reference standard 11

12. GFR iohexol and eGFR in older persons Mean difference (+SD) in ml/min Mean difference (+SD) in % n with 0-10% difference n with 10-30% difference n with >30% difference Iohexol- MDRD -7.8 (29)-16 (55)4/36 (11%)9/36 (25%)23/36 (64%) Iohexol- CG +13.6 (25)+30 (44)6/36 (17%)13/36 (36%)17/36 (47%) Iohexol- CKD_EPIcys -8.0 (25)-18 (47)6/36 (17%)9/36 (25%)21/36 (58%) Iohexol- CKD_EPIcreat -2.4 (22)-6 (48)9/36 (25%)8/36 (22%)19/36 (53%) Iohexol-CKD_EPIcreatcyst +8.4 (25)+18 (47)8/36 (22%)11/36 (31%)17/36 (47%) 12

13. Protocol of Belgian iohexol study 13

14. Protocol of Belgian iohexol study - To develop a simplified Iohexol protocol with 1-3 blood collections to measure the exact GFR that could be used for subjects of all ages (adolescents, adults, the elderly and the very elderly). - To develop and validate new and existing equations to estimate the renal function in different age groups using serum values (creatinine, cystatin C and others) and clinical parameters, including age, gender and body composition parameters. 14

15. Dried Blood Spots 15

16. Discussion “Maybe we should stop trying to transform lead into Gold” What are alternatives for creatinine and Cystatin C based equations? – a better endogenous marker – body composition parameters – the slow time constant, Why don’t we choose to simplify the iohexol clearance? – cheap, available and easy to use, very few side-effects – Using HPLC, only limited doses (5 ml) are needed. – Iohexol is very stable in serum, assuring safe transportation of the samples towards the laboratory. – Dried capillary blood spots 16

17. 5. Questions and remarks 17

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