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ROD study group

ROD study group. K. Cransberg, N. Godefroid, L. Koster, K. N Schoenmaker and M. Van Dyck. Renal osteodystrophy First report Research questions CKD and bone health Proposal add-on studies. Part 1 Renal osteodystrophy. NKF/DOQI . CKD-MBD

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ROD study group

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  1. ROD study group K. Cransberg, N. Godefroid, L. Koster, K. N Schoenmaker and M. Van Dyck

  2. Renal osteodystrophy • First report • Research questions • CKD and bone health • Proposal add-on studies

  3. Part 1 Renal osteodystrophy

  4. 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

  5. Secundaryosteoporosis Hormonal therapy glucosteroids, thyroid hormone aromataseinhibitors, ovariansuppressing agents androgendeprivationtherapy, thiazolidiniones Psychotropic and anticonvulsanttherapy selectiveserotoninreuptakeinhibitors anticonvulsants Drugsused for cardiovasculardiseases heparin, oral AC, loopdiuretics Drugstargeted the immune system calcineurininhibitors, anti-retroviraltherapy Drugsused for gastro-intestinal diseases proton pumpinhibitors Maziotti G et al. The American Journal of Medicine 2010;123:877-884

  6. 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

  7. DXA scan Z score (correctedforage and sex) > -1,5 = nosigns -1,5 and -2 = osteopenia >-2 = osteoporosisorosteopeniawithfractures References, devices Smallchildren Henwood 2009 Zemel B et al, 2007

  8. B C A Cortical Bone: Geometry & Strength Mass (gm) A = B = C Density (gm/cm3) A = B = C Strength [p(RP4 - RE4)] A << B << C

  9. 25 OH Vit D storage levelsnormal values 25 (OH)D serum <10 ng/ml (25nmol/l) severe deficient <30 ng/ml (75nmol/l) 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)

  10. Part 2 First report - treatment policy - available data ? - first results

  11. Policies ROD 2007: Management policies No questions asked about ROD 2011: What do we want to know? How are we working on ROD?

  12. Entry rich-q HD: 80 PD: 111 Tx : 54 August 2011 HD: 40 PD: 47 Tx: 158 Patients (n=245) prevalent 122, incident 123 Incident 0-3 mo RRT at MO New prevalent 3-12 mo RRT at MO Old prevalent > 12 mo RRT at MO

  13. Growth (M0) only caucasian, dialysis:

  14. X ray hand (dialysis)

  15. DXA scan (nl Z Scores)

  16. Femur z score vs phosphate in dialysis Lumbal Z score wv Alkaline phosphatase (dialyse M0) n=11! Femur z score vs PTH in dialysis R=-0.08 R=0.12 Alk.phos. Vs Calcium Alk.phos. Vs iPTH , dialyse R=-0.127 R= 0.37

  17. Phosphate binder

  18. Vitamin D (dialysis)

  19. Part 3 Research Questions

  20. 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?

  21. 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?

  22. Important questions • Methods of evaluation Ca-P metabolism? Ook 1,25 en vit D bepalen? hoe vaak? • What is the role of Vit D/ 25 (OH)D in the calcium-phosphate metabolism? • FGF23 is key player in CKD • 1-84 PTH ?

  23. Part 4 CKD and bone health Lab measurements:pitfalls Investigation of bone health

  24. 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

  25. Bone health at adult height Valta 2010 uz Nl values vit D and 1,25 Vit D Abstract ESPN2011

  26. Part 5. Proposal Add-on studies

  27. 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 • vit D in ESRD • bone health and FGF23 • ROD and transplantation

  28. 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)

  29. FGF23 Van Husen 2010 Gutierrez 2010 Parker 2010

  30. Vit D in ESRD • Rationale • Cardiovascularmorbidity and mortality in ESRD • Vit D deficiency is commonbutnovalidated data in CD children • Vit deficiency is associatedwithendothelialdysfunction • Research questions (1) - prevalence 25 OH deficiency - prevalence in black skin - associationwith lab (Ca, P, PTH, FGF23, Rx) MJS Oosterveld en JW Groothoff, AMC Amsterdam

  31. 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

  32. 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 keyplayer in the development of CKD-bonemineral disorder • FGF23 maybe a predictor of adverseclinicaloutcomes in CKD • PTH 1-84 is a more physiological parameter in CKD M. Van Dyck, R. Lombaerts, E Levtchenko, UZ Leuven

  33. Body health and FGF23 in ESRD • Research Questions • relation bone health (DXA, Rx) and FGF23, vit D • bone health : longitudinal evolution after Tx • FGF23 and growth( biometry, puberal score, IGF1) FGF23 – 25-OH vit D- 1,25 OH- PTH1-84 on specimens

  34. Part 2 studytransplantation K. Cransberg

  35. Discussion- questions

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