PTH and KDIGO Guidelines - SULM · that may increase PTH, but to know whether an apparently healthy...

PTHPTH and KDIGO Guidelinesand KDIGO Guidelines

Dr Etienne CavalierDr Etienne CavalierDepartmentDepartment of of ClinicalClinical ChemistryChemistry

UniversityUniversity of Liof Li èège, CHU Sartge, CHU Sart --TilmanTilmanLiLi èège, ge, BelgiumBelgium

Am J Kidney Dis. 2003 Oct;42(4 Suppl 3):S1-201.K/DOQI clinical practice guidelines for bone metaboli sm and disease in chronic

kidney disease.National Kidney Foundation

KDOQI Guidelines:

Maintain PTH levels between150 and 300 pg/mL

These recommandations were based on the Allegro assay, which is no longer

available.

What do we really measure with a PTH assay?

PTH (1-84)

Amino-PTHFragments C-terminaux

PTH (7-84)

RIA de 1ère génération

PTH (1-84) PTH (7-84)


PTH de 2ème génération (intacte)PTH (1-84) PTH (7-84)


PTH de 3ème génération

PTH (1-84) PTH (7-84)


Souberbielle JC, Kidney Int, 2006.

KDIGO GuidelinesAugust 2009

Is it the solution?

Question:

How should we establish the referencerange in the Laboratory?

Actually:

One one hand (ISO 15 189 Gudeline)« Laboratories should verify the reference

range proposed by the Manufacturers »

On the other hand (inserts of kits)« Laboratories should establish their own

reference range »

Establishment of the referencerange.

However…

When establishing reference values for serum PTH, itseems logical to exclude from the reference population anyperson with a condition potentially leading to an increasedPTH concentration. VitaminVitamin D D insufficiencyinsufficiency isis one condition one condition thatthat maymay increaseincrease PTH, but to know PTH, but to know whetherwhether an an apparentlyapparentlyhealthyhealthy individualindividual isis vitaminvitamin DD--insufficientinsufficient, , serumserum 25OHD 25OHD must must bebe measuredmeasured. . HoweverHowever, , vitaminvitamin D D statusstatus has not been has not been takentaken intointo accountaccount in in mostmost publishedpublished studiesstudies on PTH on PTH referencereference valuesvalues..

Souberbielle JC, Clinical Chemistry, 2005

Methods Reference range (Manufacturer)

(pg/ml)

Lower and Upper Reference limits (95% Confidence –Interval) obtained in our

reference population(pg/mL)

2nd generation assays

Abbott Architect 15.0 - 68.3 16.3 - 64.7

Beckman Access 12 - 88 10.1 - 47.4

DiaSorin N-tact IRMA 13 – 54 7.2 - 35.7

DiaSorin Liaison N-tact 17.3 - 72.9 21.3 - 68.2

Ortho Vitros 7.5 - 53.5 10.8 - 47.5

Roche Elecsys 15 - 65 13.7 - 50.2

Scantibodies Total intact PTH 14 - 66 7.8 - 49.7

Siemens Immulite 12 - 65 5.4 - 57.1

3rd generation assays

DiaSorin Liaison 1-84 5.5 - 38.4 4.6 - 25.8

Scantibodies Ca-PTH IRMA 5 - 39 6.8 - 30.8

< 150 pg/ml nb of patients (% of the total

population)

150 - 300 pg/ml nb of patients (% of the total

population)

>300 pg/ml nb of patients (% of the total

population)

Abbott Architect27

(18.1)36

(24.2)86

(57.7)

Beckman Access40

(26.8)46

(30.9)63

(42.3)

DiaSorin N-tact IRMA75

(50.3)38

(25.5)36

(24.2)

DiaSorin Liaison N-tact35

(23.5)31

(20.8)83

(55.7)

Ortho Vitros43

(28.9)47

(31.5)59

(39.6)

Roche Elecsys40

(26.9)48

(32.2)61

(40.9)

Scantibodies Total intact PTH

51(28.2)

28(18.8)

70(53.0)

Siemens Immulite37

(24.8)29

(19.5)83

(55.7)

3rd generation assays

DiaSorin Liaison 1-8472

(48.3)46

(30.9)31

(20.8)

Scantibodies Ca-PTH IRMA

65(43.6)

39(26.2)

45(30.2)

KDIGO range according

to the manufacturer

(pg/mL)

< 2x upper normal nb of patients (% of the total

population)

2 - 9x upper normalnb of patients (% of the total

population)

>9x upper normal nb of patients (% of the total

population)

Abbott Architect 137 – 61525

(16.8)84

(56.4)40

(26.8)

Beckman Access 176 – 79251

(34.2)86

(57.7)12

(8.1)

DiaSorin N-tact IRMA

108 – 48650

(33.6)88

(59.0)11

(7.4)

DiaSorin Liaison N-tact

146 – 65635

(23.5)94

(63.1)20

(13.4)

Ortho Vitros 107 – 48135

(23.5)80

(53.7)34

(22.8)

Roche Elecsys 130 – 58539

(26.2)85

(57.0)25

(16.8)


132 – 59436

(24.2)77

(51.7)36

(24.1)

Siemens Immulite 130 – 58531

(20.8)79

(53.0)39

(26.2)


77 – 34639(26.2)

85(57.0)

25(16.8)


78 – 35134

(22.8)77

(51.7)38

(25.5)

KDIGO range according

our reference range(pg/mL)

< 2x upper normal nb of patients (% of the total

population)

2 - 9x upper normalnb of patients (% of the total

population)

>9x upper normal nb of patients (% of the total

population)

Abbott Architect 129 – 58224

(16.1)82

(55.0)43

(28.9)

Beckman Access 95 – 42726

(17.5)82

(55.0)41

(27.5)


71 – 32136

(24.2)82

(55.0)31

(20.8)


136 – 61333

(22.1)91

(61.1)25

(16.8)

Ortho Vitros 95 – 42827

(18.1)84

(56.4)34

(25.5)

Roche Elecsys 100 – 45128

(18.8)82

(55.0)39

(26.2)


99 – 44728

(18.8)77

(51.7)50

(29.5)

Siemens Immulite 114 – 51320

(13.4)78

(52.4)51

(34.2)


52 – 23227

(18.1)78

(52.4)44

(29.5)


62 – 27730

(20.1)70

(47.0)49

(32.9)

2nd generation assays 3rd generation assays

Abbott Architect

BeckmanAccess



Ortho Vitros

Roche Elecsys

Scantibodies

Total intact PTH

Siemens Immulite


Scantibodies

Ca-PTH IRMA

AbbottArchitect

X 0.391 0.387 0.731 0.820 0.632 0.833 0.910 0.670 0.877

BeckmanAccess

0.954 X 0.975 0.704 0.569 0.735 0.563 0.488 0.704 0.521

DiaSorinN-tact IRMA

0.731 0.775 X 0.701 0.566 0.733 0.561 0.485 0.702 0.519


0.687 0.733 0.895 X 0.837 0.926 0.805 0.747 0.891 0.782

OrthoVitros

0.909 0.954 0.819 0.777 X 0.817 0.967 0.912 0.853 0.945

RocheElecsys

0.628 0.672 0.897 0.929 0.715 X 0.844 0.730 0.809 0.764

ScantibodiesTotal intact PTH

0.879 0.879 0.709 0.670 0.857 0.612 X 0.924 0.844 0.956

SiemensImmulite

0.989 0.943 0.721 0.678 0.897 0.619 0.890 X 0.766 0.967

DiaSorinLiaison

1-840.955 0.955 0.757 0.716 0.933 0.656 0.924 0.966 X 0.858

Scantibodies

Ca-PTH IRMA

0.869 0.869 0.742 0.705 0.847 0.645 0.968 0.880 0.913 X

The overall agreement is significantly higher among the different methods when the Laboratory’s refere nce ranges are used (Kappa=0.816 vs. 0.749, p

0

200

400

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1600

0 100 200 300 400 500 600 700

DiaSorin Liaison PTH (1-84)

Abb

ott A

rchi

tect

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0 100 200 300 400 500 600 700


Abb

ott A

rchi

tect

0

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0 100 200 300 400 500 600 700


Abb

ott A

rchi

tect

0

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0 100 200 300 400 500 600 700


Abb

ott A

rchi

tect

So,

• It is clearly better to use multiples of the upper reference range instead of a « fixed » limit.

• (1-84) PTH can be used for the follow-up of the CKD-5D patients as any other iPTHassay.

Future perspectives

• Establish the reference range of all the PTH assays in different populations (Afro-American, Asians,…) according to different other parameters (BMI, Age,…) in a multicentre study.

• Use specific bone markers for CKD-5D patients, like bAP as recommended by the KDIGO (or even TRAP-5B and intact P1NP): indeed, PTH is not a « real » bonemarker…

Variation of bAP and PTH values on a 6-weeks period according to the

critical difference concept

Delanaye et al, submitted.

ΔPTH (%)

ΔBAP (%)

Thank you for your attention!

PTH and KDIGO Guidelines - SULM · that may increase PTH, but to know whether an apparently healthy...

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