Post on 22-Oct-2020
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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)
Amino-PTHFragments C-terminaux
PTH de 2ème génération (intacte)PTH (1-84) PTH (7-84)
Amino-PTHFragments C-terminaux
PTH de 3ème génération
PTH (1-84) PTH (7-84)
Amino-PTHFragments C-terminaux
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)
Scantibodies Total intact PTH
132 – 59436
(24.2)77
(51.7)36
(24.1)
Siemens Immulite 130 – 58531
(20.8)79
(53.0)39
(26.2)
DiaSorin Liaison 1-84
77 – 34639(26.2)
85(57.0)
25(16.8)
Scantibodies Ca-PTH IRMA
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)
DiaSorin N-tact IRMA
71 – 32136
(24.2)82
(55.0)31
(20.8)
DiaSorin Liaison N-tact
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)
Scantibodies Total intact PTH
99 – 44728
(18.8)77
(51.7)50
(29.5)
Siemens Immulite 114 – 51320
(13.4)78
(52.4)51
(34.2)
DiaSorin Liaison 1-84
52 – 23227
(18.1)78
(52.4)44
(29.5)
Scantibodies Ca-PTH IRMA
62 – 27730
(20.1)70
(47.0)49
(32.9)
2nd generation assays 3rd generation assays
Abbott Architect
BeckmanAccess
DiaSorin N-tact IRMA
DiaSorin Liaison N-tact
Ortho Vitros
Roche Elecsys
Scantibodies
Total intact PTH
Siemens Immulite
DiaSorin Liaison 1-84
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
DiaSorin Liaison N-tact
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
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0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
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0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
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0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
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1400
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0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
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1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
Abb
ott A
rchi
tect
0
200
400
600
800
1000
1200
1400
1600
0 100 200 300 400 500 600 700
DiaSorin Liaison PTH (1-84)
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!