Transcript Adequacy studygroup - Rich-Q

ROD study group
K. Cransberg, N. Godefroid, L. Koster, K.
N Schoenmaker and M. Van Dyck
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Renal osteodystrophy
First report
Research questions
CKD and bone health
Proposal add-on studies
Part 1 Renal osteodystrophy
NKF/DOQI
CKD-MBD
A systemic disorder of mineral and bone
maturuation due to CKD manifested by either one
or a combination of the following
- abnl Ca, P, PTH and vit D metabolism
- abnl in bone turnover, mineralization, volume,
linear growth, or strength
- vascular or soft-tissue calcification
Renal osteodystrophy
An alteration of bone morpholgy
low turnover, high turnover, mixed lesions
Secundary osteoporosis
Hormonal therapy
glucosteroids, thyroid hormone
aromatase inhibitors, ovarian suppressing agents
androgen deprivation therapy, thiazolidiniones
Psychotropic and anticonvulsant therapy
selective serotonin reuptake inhibitors
anticonvulsants
Drugs used for cardiovascular diseases
heparin, oral AC, loop diuretics
Drugs targeted the immune system
calcineurin inhibitors, anti-retroviral therapy
Drugs used for gastro-intestinal diseases
proton pump inhibitors
Maziotti G et al. The American Journal of Medicine 2010;123:877-884
Guidelines NKF/DOQI
CKD 5
monthly Ca, P, bic, AP, PTH
25(OH) vit D at least annually
Rx Bone every 6-12 months
Stages 1-5 T
25 OH and then based on level of
treatments (2C)
EPDWG
DXA scan
Z score (corrected for age and sex)
> -1,5 = no signs
-1,5 and -2 = osteopenia
>-2 = osteoporosis or osteopenia with fractures
References, devices
Small children
Henwood 2009
Zemel B et al, 2007
Cortical Bone: Geometry & Strength
A
B
C
Mass (gm)
A = B = C
Density (gm/cm3)
A = B = C
Strength [p(RP4 - RE4)] A << B << C
25 OH Vit D storage levels
normal values 25 (OH)D serum
<10 ng/ml (25nmol/l)
<30 ng/ml (75nmol/l)
severe deficient
deficiency
>30 ng/ml (75nmol/l)
desirable for optimal growth
(30-50)
>80 ng/ml (200 nmol/l) toxic > hyperCa
Vit D deficiency is a worldwide health problem
>> skeletal disorders + cardiovascular disease
Vit D deficiency is a risk factor for hyperparathyroidism
(independent of 1.25 OH2D)
Part 2 First report
- treatment policy
- available data ?
- first results
Policies ROD
2007: Management policies
No questions asked about ROD
2011: What do we want to know?
How are we working on ROD?
Patients (n=245)
Entry rich-q
HD: 80
PD: 111
Tx : 54
August 2011
HD: 40
PD: 47
Tx: 158
prevalent 122, incident 123
Incident
New prevalent
Old prevalent
0-3 mo RRT at MO
3-12 mo RRT at MO
> 12 mo RRT at MO
Growth (M0)
only caucasian, dialysis:
Group
Length <-2.5 Growth
SD
hormone use
incident
16/61= 26%
15/61=24%
Prevalent new
10/33= 30%
8/33=24%
Prevalent old
20/44= 45%
22/45=49%
X ray hand (dialysis)
Group
ROD signs
incident
10/57= 18%
Prevalent new
6/37= 16%
Prevalent old
22/61= 36%
DXA scan (nl Z Scores)
Dialysis
Incident
Prevalent
femur
5 (83%)
21/26 (77%)
Lumbar spine
5 (100%)
31/38 (82%)
Total body
0
12 /15 (86%)
Femur
4 (100%)
9/18 (50%)
Lumbar spine
5 (63%)
24/33 (73%)
Total body
3 (50%)
7/13 (54%)
Transplantation
Femur z score vs PTH
in dialysis
Femur z score vs
phosphate in dialysis
Lumbal Z score wv Alkaline
phosphatase (dialyse M0) n=11!
R=-0.08
R=0.12
Alk.phos. Vs Calcium
R=-0.127
Alk.phos. Vs iPTH , dialyse
R= 0.37
Phosphate binder
Phosphate
binders
Both
Incident
N (%)
10 (14%)
Prevalent
N (%)
30 (27%)
Only Ca based 21 (29%)
26 (23%)
Only non
17 (24%)
calcium based
None
24 (33%)
35 (31%)
21 (19%)
Vitamin D (dialysis)
Vitamin D
Incident
N (%)
Prevalent
N (%)
Multi vit
28 (53%)
44 (45%)
Vit D/ D cure
/dagravit
5
(9%)
6 ( 6%)
Vit D3
(etalpha etc)
59 (82%)
88 (79%)
Part 3 Research Questions
Diagnosis;
Does your centre check Vitamin D regularly?
How often?
DEXA scan:
How often is a DEXA scan preformed?
Which type of DEXA scan is used?
How are the results reported?:
BMD/ Z score/ T score/ other?
Which normal values are used?
X ray hand:
How often is a Hand X ray performed?
For children treated with PD? HD? Tx?
How are the results reported?
Open text or for example “no signs of ROD”
Definition of no/moderate/ severe signs of ROD?
Other diagnostic tools?
Diagnosis;
Medications
Growth standards
Fracture rate
Prevention ROD:
What kind of babymilk is prescribed? Low phosphate?
Vit D therapy, dosage, orally or IV?
Vit D after transplantation?
Important questions
1. Methods of evaluation Ca-P metabolism?
Ook 1,25 en vit D bepalen?
hoe vaak?
2. What is the role of Vit D/ 25 (OH)D in the
calcium-phosphate metabolism?
3. FGF23 is key player in CKD
4. 1-84 PTH ?
Part 4 CKD and bone health
Lab measurements:pitfalls
Investigation of bone health
Accumulation of non(1-84) PTH in progressive CKD
Non(1-84)PTH = 20 % in nll GFR but increases to 50 % in CKD
(1-84)PTH= 20% van dit intact PTH in nl GFR, but 5% b in CKD
Dr K. Van Aerschot, Prof E. Levtchenko
Bone health at adult height
Valta
2010
uz
Results uzleuven
Group A(GH+, n=15))
Group B (GH-, n=6)
P value
Final Height SDS
-0.5 (-2.3 to 1.0)
-0.18 (-0.93 to 0.81)
0.40
BMI SDS
-0.5 (-2.5 to 1.0)
0.22 (-0.44 to 1.79)
0.05
sLBMDL2-4 (mg/cm2)
1026 (859 to 1154)
1045(711 to1140)
0.49
T score sLBMD
-1.3(-2.9 to 0.2)
-1.15 (-3.8 to -0.2)
0.49
% lean body mass
80.7(65.2 to 86.0)
72.6(57.4 to 79.6)
0.01
Nl values vit D and 1,25 Vit D
Abstract ESPN2011
Part 5. Proposal Add-on studies
ROD studies in RICH-Q group
• Cinacalcet 20070208 (AMGEN) will
be started in chronic dialysis patients
6-18 yrs of age
• Proposal add-on studies
1.vit D in ESRD
2. bone health and FGF23
3.ROD and transplantation
Cinacalcet
Cinacalcet 20070208 will be started in dialysis
patients 6-18 yrs of age
1. reducing the plasma PTH by 30 %
2. lowering PTH < 300 pg/ml
impact on S Ca, Ca ion, Ca-P product
impact on growth
60 weeks
- double-blind dose titration phase(24 wks)
-double-blind efficacy assessment phase(6 wks)
-open-label dose titration phase (24 wks)
-open-label maintenance phase (6 wks)
FGF23
Gutierrez 2010
Van Husen 2010
Parker 2010
Vit D in ESRD
• Rationale
– Cardiovascular morbidity and mortality in ESRD
– Vit D deficiency is common but no validated
data in CD children
– Vit deficiency is associated with endothelial
dysfunction
• Research questions (1)
- prevalence 25 OH deficiency
- prevalence in black skin
- association with lab (Ca, P, PTH, FGF23,
Rx)
MJS Oosterveld en JW Groothoff, AMC Amsterdam
Vit D in ESRD
• Research Questions(2)
- current practice of supplementation
- effect of vit D3 addition
° Ca, P, iPTH and FGF23
° occurrence of ROD
° relation to endothelial function
MJS Oosterveld en JW Groothoff, AMC Amsterdam
Body health and FGF23 in ESRD
• Rationale
– FGF23 regulate P metabolism . In CKD both FGF23
(active and inactive)and PTH are increased.
– FGF23 is a key player in the development of CKDbone mineral disorder
– FGF23 may be a predictor of adverse clinical
outcomes in CKD
– PTH 1-84 is a more physiological parameter in CKD
M. Van Dyck, R. Lombaerts, E Levtchenko, UZ Leuven
Body health and FGF23 in ESRD
• Research Questions
1. relation bone health (DXA, Rx) and FGF23,
vit D
2. bone health : longitudinal evolution after Tx
3. FGF23 and growth( biometry, puberal
score, IGF1)
FGF23 – 25-OH vit D- 1,25 OH- PTH1-84 on
specimens
Part 2 study transplantation
K. Cransberg
Discussion- questions