Chronic Kidney Disease–Mineral and Bone Disorder (CKD-MBD): Current Perspectives

Figures & data

Table 1 Recommended Guidelines by Different Professional Groups

Group	Year	Recommended Levels
		Corrected Calcium (mg/dL)	Phosphorous (mg/dL)	PTH (pg/mL)
KDIGO^Citation17	2017	Near normal range	Near normal range	2–9× upper limit of normal
KDIGO^Citation18	2009	Within normal range	Within normal range	2–9× upper limit of normal
K/DOQI^Citation15	2003	8.4–9.5	3.5–5.5	150–300
Canadian Society of Nephrology^Citation19	2006	Within normal range	Within normal range	100–500
Japanese Society for Dialysis Therapy^Citation20	2008	8.4–10.0	3.5–6.0	60–240
UK Renal Association^Citation21	2002	8.8–10.4	<5.6	<4× upper normal range

Figure 1 Pathogenesis of disordered mineral metabolism in CKD.

Abbrevaitions: CaR, calcium-sensing receptor; FGFR, fibroblast growth factor receptor; PTH, parathyroid hormone; VDR, vitamin D receptor.

Notes: (A) Traditional view of the mechanisms that maintain secondary hyperparathyroidism in advanced chronic kidney disease. (B) Updated view of the mechanisms that initiate secondary hyperparathyroidism in chronic kidney disease, emphasizing the central role of FGF23. Reprinted from Kidney International, 78(10). Isakova T, Wolf MS. FGF23 or PTH: which comes first in CKD? Kidney Int. 2010;78(10):947–9, Copyright 2010, with permission from Elsevier.

Table 2 Markers of Bone Turnover

Marker	Tissue of Origin	Specimen	Comments
Bone Formation
Specific bone alkaline phosphatase (b-ALP)	Bone	Serum	Glycoprotein derives from osteoblasts. Good surrogate marker of bone formation.
Osteocalcin (OC)	Bone, Platelets	Serum	Originates from osteoblasts, odontoblasts and hypertrophic chondrocytes. Plays a vital role in osteoid mineralization.
C-terminal propeptide of type I procollagen (PICP)	Bone, soft tissue, skin	Serum	Arises from proliferating osteoblasts and fibroblasts. Not recommended for routine use as a marker of mineral bone disorders.
N-terminal propeptide of type I procollagen (PINP)	Bone, soft tissue, skin	Serum	Arises from proliferating osteoblast and fibroblasts.
Bone Resorption
Hydroxyproline	Bone, cartilage, soft tissue, skin	Urine	Present in both the newly synthesized and the mature collagen.
Hydroxylysine glycosides	Bone, soft tissue, skin, serum & complement	Urine, serum	Hydroxylysine in collagen is glycosylated to varying degrees, depending on tissue type
Carboxyterminal crosslinked telopeptide of type I collagen (CTX-I)	Tissues containing type I collagen	Urine (a-/s), serum (s only)	Collagen type I, predominantly from the bone. Isomerisation of aspartyl to s-aspartyl occurs with ageing of collagen molecule.
Aminoterminal crosslinked telopeptide of type I collagen (NTX-I)	Tissues containing type I collagen	Urine, serum	Collagen type I, predominantly from the bone.
Bone Sialoprotein (BSP)	Bone, dentin, hypertrophic cartilage	Serum	Synthesized by osteoblasts and osteoclastic cells.
Tartrate-resistant acid phosphatase (TRAcP)	Bone, blood	Plasma, serum	Six isoenzymes are present in the human tissues. Expressed by Osteoclasts, dendritic cells and macrophages. TRAcP 5b is considered as a marker of bone resorption, while TRAcP 5a is a known marker of inflammatory conditions.

Note: Modified from Clinical Biochemist Reviews. 2005;26(4):97-122. Seibel MJ. Biochemical markers of bone turnover: part 1: biochemistry and variability, with permission from the author and publisher of Clinical Biochemist Reviews.⁵²

Table 3 The Relationship Between Traditional Markers of CKD-MBD (PTH, Phosphate and Calcium) and Mortality

Author, Year	Study Design	Dialysis Modality	Risk of Mortality with Markers of CKD-MBD
			Calcium		Phosphate		PTH
			Low	High	Low	High	Low	High
Block et al 2004^Citation57	Retrospective	HD	Decreased	Increased	NS	Increased	NS	Increased
Noordzij et al 2005^Citation53	Prospective	HD, PD	NS	NS	NS	Increased	NS	NS
Kalantar-Zadeh et al 2006^Citation55	Prospective	HD	Increased	Increased	Increased	Increased	Increased	Increased
Melamed 2006^Citation63	Prospective	HD, PD	NS	Increased	NS	Increased	NS	Increased
Tentori et al 2008^Citation61	Retrospective	HD	Increased	Increased	Increased	Increased	Increased	Increased
Block et al 2010^Citation64	Prospective	HD	NS	Increased	NS	Increased	NS	Increased
Floege et al 2011^Citation60	Prospective	HD	Increased	Increased	Increased	Increased	Increased	Increased
Soohoo et al 2016^Citation56	Retrospective	HD	NS	Increased	Increased	Increased	Increased	Increased
Waziri et al 2019^Citation54	Prospective	HD, PD	NS	Increased	NS	Increased	NS	Increased

Abbreviations: HD, hemodialysis; PD, peritoneal dialysis; NS, not significant.

Figure 2 Hazard ratios of plasma fibroblast growth factor 23 with mortality by various studies.

Note: *Reported odd ratio.

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