CKD-MBD

Chronic Kidney Disease – Mineral Bone Disorder

Dr. R. Daelemans ZNA Nierkliniek

CKD-MBD

1. Definitie en diagnose

2. Fysiopathologie

3. Gevolgen

4. Behandeling

2

Chronic Kidney Disease: risk of death and CV events Go, NEJM 2004

Go, NEJM 2004

Foley, Am J Kidney Dis 1998

The definition, classification and prognosis of CKD: a KDIGO report

Levey A. Kidney Int 2011

‘systeemaandoening’ door interactie tussen

nier, bijschildklier, bot, GI tractus, CV systeem

• calcium, fosfaat, PTH, vit D

• botmetabolisme:

- FGF-23

- osteïtis fibrosa

- osteomalacie / adynamisch bot

• vasculaire en klep calcificaties

Moe, Kidney Int 2006

CKD – MBD: DIAGNOSE

• Labo: P, Ca, 25OH vitD,

PTH (FGF-23)

• Calcificaties:

• RX abdomen

• CT, MRI

• Echocardio

• Botbiopsie

CKD – MBD: FYSIOPATHOLOGIE

P vit D

PTH

Secundaire hyperpara

NIERFUNCTIE

10

CKD Nier: P excretie P Bot: Ca, P vrijstelling

Nier: vit D Klotho Bot: FGF-23 Bijschildklier:PTH

Darm: Ca absorptie Darm: P absorptie Nier: P excretie

Phosphorus, PTH and FGF-23 in CKD Isakova, Kidney Int 2011

Time profile of changes in P, PTH, vit D, FGF-23 and Klotho

John, Am J Kidney Dis 2012

Serum Phosphorus and the incidence of CV disease in the community

Dhingra, Arch Intern Med 2007

25 OH vitamin D and cardiovascular disease risk

Wang, Circ Cardiovasc Outcomes 2012

Vitamine D: update 2013 Gröber, Dermato-Endocrinol 2013

PTH levels and cardiovascular disease risk Thompson, Nat Rev Endocrinol 2013

FGF-23 and mortality in hemodialysis patients

FGF-23 FGF-23

PTH

1,25 OH vit D

RAAS

KLOTHO

inflammatie

LVH

Guttierez, NEJM 2008

FGF-23 and CV mortality in the community

Arnlov, Kidney Int 2013

Arterial calcification: role of the bone vascular axis

Thompson, Nat Rev Endocrinol 2013

Arterial calcification: role of the bone-vascular axis

Thompson, Nat Rev Endocrinol 2013 PROMOTOREN

• P, Ca, FGF-23

• vit D

INHIBITOREN

MGP

FetuinA

Magnesium

VSMC

OSTEOBLAST

23

24

CKD-MBD: BEHANDELING

DOEL

CKD: normaliseren P, Ca, 25OH vit D, PTH

Dialyse: normaliseren P, Ca, 25OH vit D

PTH: 150-300 pg/mL

CKD-MBD in Europe: cosmos study Fernandez-Martin, NDT 2013

CKD-MBD: BEHANDELING

1. Fosfaatbeperkend dieet

2. Fosfaatbinders

3. Behandelen hyperparathyroïdie - vitamine D

- calcimimetica

- parathyroïdectomie

CKD-MBD: BEHANDELING

CALCIUMZOUTEN NIET CALCIUMHOUDENDE P BINDERS

• Ca carbonaat, Ca acetaat

• Ca acetaat (Phoslo®)

• Ca acetaat + Mg carbonaat (Renepho®)

• Sevelamer (Renagel®, Renvela®)

• Lanthanum (Fosrenol® )

FOSFAATBINDERS

Phosphate-binding agents lower risk of mortality

Cannata-Andia, Kidney Int 2013

Effects of calcium-based versus non-calcium based phosphate binders on mortality: a meta-analysis

Jamal S, Lancet 2013

Sevelamer: effects in CKD Rastogi, Ther Adv Cardiovasc Dis 2013

Renagel, Renvela

Magnesium and outcomes in patients with CKD

Massy, Clin Kidney J 2012

• HypoMg and coronary artery

calcifications (Framingham

Heart Study)

Hruby JACC 2014

• HypoMg, risk of death and

GFR decline

Van Laecke S Am J Med 2013

Mg belet mineralisatie van VSMC door expressie MGP

CKD - MBD: BEHANDELING

VITAMINE D

VOEDING

Huid: UV cholecalciferol (D3) ergocalciferol (D2)

LEVER

25-OH Vit D

NIER

1,25 (OH) 2 vit D

CKD - MBD: BEHANDELING

VITAMINE D

Cholecalciferol D3 (D-Cure®) Actief vit D

Alfacalcidol (1 Alpha Leo®)

Calcitriol (Rocaltrol®)

Vitamin D treatment in CKD: a meta-analysis

Duranton, Am J Nephrol 2013

CKD – MBD: BEHANDELING

CALCIMIMETICA: Cinacalcet (Mimpara®)

PTH en FGF-23

(Echo study)

calcificaties

(Advance study) mortaliteit

(Evolve study)

CKD – MBD: BEHANDELING

PARATHYROIDECTOMY

Naranda J Int Med Res 2011 Goldenstein Plosone 2013

Ca supplements and risk of myocardial events

Bolland, BMJ 2010

39

CKD - MBD: VITAMINE K

• CKD vit. K deficiëntie

MGP

• Vit K antag: coumarines vit K depletie inhibitor calcificaties

calcificaties

• Substitutie vit K: minder klep calcificaties

Shurgers L Kidney Int 2013

Krüger Semin Dial 2014

Zhang J Cardiovasc Pharmacol 2014

BESLUIT

1. CKD – MBD CV mortaliteit

2. Diagnose (vroegtijdig): Ca, P, 25OH vit D, PTH, (FGF-23), calcificaties

3. Behandeling: dieet, fosfaatbinders, vitamine D, calcimimetica, PTx

INDIVIDUEEL hyperCa, calcificaties, hoog PTH

ronald.daelemans@zna.be

www.zna.be/nefrologie