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Assessing renal function in the elderly The development of a new Iohexol based method to measure

the true Glomerular Filtration RateGijs Van Pottelbergh, (MD, PhD)

BelgiumPromotor: Prof. Dr. Jean Marie Degryse (KULeuven en UCL)

Co-Promotor: Prof. Dr. Pierre Wallemacq (UCL)

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1. Introduction: The renal function

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Estimating the renal function in older persons: recent evolutions

2008 IDMS MDRD equation

eGFR = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if black)

2009 CKD-EPIcreat

eGFR = 141 x min (Scr/k,1)a x max (Scr/k,1)-1,209 x 0,993Age 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 0.995age [ x 0.969 if female ] [ x 1.08 if black ]

2012 Berlin Initiative study:

eGFR=767 x Scys-0.61 x Scr-0.40 x age-0.57[ x 0.82 if female ]

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Chronic kidney disease

Stage Description 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*

3 Moderate reduction in GFR 30-60

4 Severe reduction in GFR CKD 15-30

5 Kidney failure <15

Table 2: CKD classification

*kidney damage = persisting proteinuria, hematuria or structural abnormalities of the kidneys

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CKD in Flanders (MDRD)

50-54 55-59 60-64 65-69 70-74 75-79 80-84 85-89 90-94 95+0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

<30 ml/min (Stage 4+5) 30-45 ml/min (stage 3B) 45-60 ml/min (stage 3A) >60 ml/min (stage 0-2)

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CKD in Russia (Crystal Data)

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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

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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

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Differences between eGFR estimations (BELFRAIL n=544)

Total matches Match<30 ml/min

Difference<10%

Difference10–20%

Difference20–30%

Difference>30%

CG-MDRD 277 (51.7%) 27/60 (45%) 9.9% 22.8% 27.2% 40.1%

MDRD-CKDEPI 517 (96.5%) 31/38 (82%) 52.1% 39.3% 6.5% 2.0%

MDRD–CystC 371 (69.2%) 21/42 (50%) 22.9% 25.4% 18.2% 21.9%

CystC–CG 267 (49.8%) 23/60 (38%) 22.9% 21.8% 17.7% 37.5%

CystC–CKDEPI 369 (68.8%) 23/47 (49%) 31.7% 28.9% 18.7% 20.6%

CKDEPI–CG 294 (54.8%) 33/57 (58%) 32.6% 29.9% 26.3% 11.2%

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GFRIohexol as reference standard

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GFRIohexol as reference standard

0 50 100 150 200 250 300 35010

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30

40

50

60

70

80

90Iohexol in serum after injection

Time (min)

Seru

m c

once

ntra

tion

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GFRiohexol 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%)

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Protocol of Belgian iohexol study

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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.

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Dried Blood Spots

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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

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5. Questions and remarks

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