1) Chronic kidney disease mineral and bone disorder (CKD-MBD) results from abnormalities in calcium, phosphorus, PTH, and vitamin D levels due to CKD. This leads to bone disease and soft tissue calcification. 2) High bone turnover disease is characterized by elevated PTH and bone formation exceeding resorption. Low bone turnover disease occurs with low or normal PTH and inadequate mineralization. 3) Treatment of CKD-MBD focuses on controlling phosphorus levels through diet and binders, treating PTH abnormalities with calcitriol or cinacalcet, and managing calcium levels. Surgical parathyroidectomy may be needed for severe or resistant cases.

1. CHRONIC KIDNEY DISEASE –
MINERAL AND BONE DISORDER
MODERATOR : DR. K.N SHARMA

2. SOURCE
• Harrison’s 21st edition page no 2313, 2314.
• Current medical diagnosis and treatment edition 2022.
• KDIGO GUDELINES 2017.

3. CLASSIFICATION OF CHRONIC KIDNEY
DISEASE
INCREASING
RISK
INCREASING RISK
NO CKD IN
ABSENCE OF
MARKER OF
KIDNEY
DAMAGE

4. DEFINITION
• Systemic disorder of mineral and bone metabolism due to
CKD manifestated as
• Abnormalities of Calcium , Phosphorus , PTH and Vitamin D.
• Abnormalities in bone turn over , mineralization , volume,
linear growth or strength.
• Vascular or other soft tissue calcification.

5. BONE DISEASE DUE TO CKD
• HIGH BONE TURN OVER DISEASE : Osteitis fibrosa cystica =
increased PTH levels.
• LOW BONE TURN OVER DISEASE : Adynamic Bone Disease =
low or normal PTH levels.
• OSTEOMALACIA : reduced effect of the active form of vit -D.

6. PATHOGENISIS OF CKD - MBD
CKD - MBD REVIEW
• FGF-23 produced from osteocytes is a potent phosphaturic
substance.
• inhibits Na+-P cotransporter in PCT and excretes out
phoshorous.

7. • FGF-23 inhibit 1 alpha hydroxylase and prevents conversion
of 25(OH)D3 to 1,25(OH)D3 (calcitriol / active form of
vitamin D3).
• causing decreased calcium and phosphorus absorption from
GIT.
• Normally, calcitriol inhibits PTH hormone and PTH stimulates
vitamin D.

8. • promotes calcification and LVH.
• Receptor in PCT for FGF-23: klothoreceptor.

9. • FGF - 23
inhibit Na+P inhibit 1- alpha hy- promotes calcifica-
cotransporter doxylase and prev- tion and LVH.
in PCT and ex- ent conversion of
crete out pho- calcidiol to calcitriol.
sphorus.
HERO VILLAN

11. PATHOGENISIS OF CKD MBD
• declining GFR leads to reduced excretion of phosphate and thus
phosphate retention.
• the retained phosphate stimulates increased synthesis of both FGF-
23 by osteocytes and of PTH and also stimulates growth of
parathyroid gland mass.
• PTH production is stimulated by decreased level of ionized calcium
which in turn result from decreased level of renal calcitriol
production with reduced kidney mass and supression of calcitriol
production due to phosphate retention and elevated level of FGF-
23 which also increases degradation of calcitriol.

12. CKD
GFR BELOW 60
Reduced renal
mass
PHOSPHATE
RETENTION
KLOTHO RECEPTOR
DEPENDANCE
(ATTENUATED IN CKD)
STIMULATE
GROWTH OF PTH
GLAND MASS
DECREASE
CALCITRIOL
INCREASE IN FGF
23
INCREASE PTH
DECREASE
CALCIUM

13. • S.calcium S.calcium
• S.calcitriol S.calcitriol
• S.phosphorus S.phosphorus
klotho resistance
secondary hyperthyroidism

14. • Secondary Hyperparathyroidism
increased bone formation and resorption
without adequate minearalization
formation of woven bone liable to fracture
easily.
• Clinically at radial side of middle and distal phalanx of
2nd and 3rd digit ( subperiosteal resorption )

15. FEATURES OF HIGH BONE TURN OVER
DISEASE
• PTH = normal value = 50-100 pg/ml
normal in CKD = 150-300 pg/ml
> 7-9 times of UL ie 600-700 pg/ml = 20 Hyper
PTH
PO4 Calcium Calcitriol
>5.5 <8.4 <30

16. • CLINICAL MANIFESTATIONS:
- bone pain and fragility
- Brown tumour
- compression syndromes
- resistance to erythropoiesis stimulating agents related to bone
marrow fibrosIs.
-Bone histology shows abnormal osteoid , bone and bone marrow
fibrosis.
-Advanced stages formation of bone cysts , sometimes with
haemorrhagic element appears bRown in colour known as BROWN
TUMOUR.

17. BROWN’S TUMOR
SUBPERIOSTEAL
EROSIONS

18. LOW BONE TURNOVER DISEASE
• PTH = < 200 pg/ml
• due to - use of vitamin - D preparations.
- increased calcium from exogenous route.
- high calcium diasylate.
• S.Calcium - Wide spread medial calcification
• S.Phosphorus - Death occur due to coronary
• Vit- D calcification

19. COMPLICATIONS OF ADYNAMIC BONE DISEASE
- Fracture
- Bony pain
- Increase vascular and cardiac calcifications
- Calcium precipitate in soft tissue into large concretions
termed as calcinosis.
CLINICAL FEATURES
- Musculoskeletal pain
- Inability to repair microfractures

20. OSTEOMALACIA
- characterized by lack of bone mineralization
- In Past = associated with aluminium toxicity due to
- chronic ingestion of prescribed aluminium
containing phosphorus binders.
- or from high level of aluminium in impure
dialysate water.
- currently = associated with Hypovitaminosis D
- also have theoretical risk of osteomalacia a/w
use of bisphosphonates in advanced CKD.

21. CALCIPHYLAXIS
• seen in advanced CKD.
• healed by painful livedo reticualris and subcutaneous nodule
that advances to patches if ischemia necrosis.
• especially on legs, thighs, abdomen and breasts.
• pathologically there is evidence of vascular occlusion in
association extensive vascular and soft tissue calcification

22. calciphylaxis

23. • Warfarin is still used in some dialysis patients in whome direct
oral anticoagulants are contraindicated, and one of the effect
of warfarin therapy is to decrease the vitamin -k dependent
activation of matrix GLA protein.
• matrix GLA protein have role in preventing vascular
calcification.
• So warfarin therapy is considered tobe a risk factor for
calciphylaxis and if a patient develop this syndrome, this
medication shoud be discontiued and alternative means of
anticoagulation should be choosen.

24. DIAGNOSIS OF CKD MBD
- Bone biopsy- GOLD STANDARD
renal osteodystrophy can be diagnosed only by bone
biopsy , which is rarely done.
A) Biochemistry
1. Serum calcium
2. Serum phosphorus
3. Vitamin D
4. IPTH
B) Radiology
X RAY hand

25. TREATMENT

26. HIGH BONE TURNOVER DISEASE
• S.Calcium + S.Phosphorus
<8.5 >5.5
• 1. control S.PO4 a) Dietery restriction-
• dietery phosphorus should be restricted to 800-1000
mg/day
- processed food
- canned food
- curd
- butter
- milk.

27. B) Phosphate binders
S.calcium < 8 >8
Calcium Acetate Sevelemer( LDL)
Calcium Carbonate Lanthrum
• New - Ferric citrate
Sucro-ferric hydroxide ( VELPHORO if GFR < 15)
Niacin tenapanar

28. PHOSPHATE BINDERS
CALCIUM BASED
- Inexpensive
-Well tolerated
-May contribute to
vascular
calcification
Examples
Calcium acetate
Calcium carbonate
NON CALCIUM BASED
-Reduced calcium
intake
-Slow vascular
calcification
Examples
Sevalamer
Lanthnum
MOA - Block absorption of dietery phosphorus in the gut
- given thrice daily with meals
- should be titrated to a near normal s.phosphorus level

29. • Calcium containing binders
- Calcium carbonate 650 mg/day
- Calcium Acetate 667 mg/day
- used at dose of one to three pills/meal
• Non- Calcium containing binders
- Sevelemer Carbonate - 800-3200 mg/meal
- Lanthanum carbonate - 500-1000 mg/meal
- Current guidelines suggest limiting their use in favour of non-
calcium containing binders.
- Newer Iron based phosphorus binders
ferric citrate may be considered when other binders
are not tolerated due to
sucroferric oxyhydroxide Hypercalcemia or constipation

30. SEVALAMER
PHOSPHORUS LEVELS
> 5.5 and <7.5 mg per
dl
800mg TDS with meals
PHOSPHORUS >7.5
1600 mg TDS
TITRATE BY 800mg per meal in 2 week interval

31. Calcium acetate 667 mg(tablets per
meal)
Sevalamer carbonate tablets
1 TABLET 800 mg
2 TABLETS 1600 mg
3 TABLETS 2400mg

32. CALCITRIOL
• Once serum phosphorus levels are well controlled ,active vitamin -
D or other vit-D analogues are used to treat secondary hyperPTH in
advanced CKD and ESKD.
• Active vit-D increases both s.calcium and s.phosphorus levels both
need to be monitered closely and its dose should be decreased if
hypercalcemia or hyperphosphataemia occurs.
• Calcitriol dosing is 0.25 or 0.5 mcg orally daily or every other day.
• Target vit- D levels -30ng/dl.
• If < 3ng/ml –supplement by ergocalciferol (vit D2) 50000 IU capsule
monthly.

33. • S.Calcium + S.Phosphorus
< 8 < 5.5
very rare - Severe Vit-D deficiency
Calcitriol 0.25 mcg alternate day

34. CINACALCET
- Cinacalcet targets the calcium sensing receptors of
parathyroid gland and and supresses PTH
production.
• Mechanism of action
- The calcium sensing receptors on the surface of
chief cell of parathyroid gland is the principal
regulator of PTH secretion.
- Cinacalcet increases the sensitivity of calcium
sensing receptor to extracellular calcium

35. DOSAGE AND ADMINISTRATION
- 30 - 90 mg once daily with food or shortly after a meal.
- can cause serious hypocalcemia.
- Serum calcium and serum phosphorus should measured with in
1 week and PTH should be measured in 1 to 4 weeks after
initiation or dose adjustment of Cinacalcet.
- Cinacalcet should be titrated no more frequently than every 2 to
4 weeks through sequential doses of 60, 90, 120 and 180 mg
once daily to target IPTH.

36. MANAGEMENT
• LOW BONE TURNOVER DISEASE
- Stop calcium and vit-D.
- Low calcium or zero disylate.
- Vit-K2 analougues.

37. PTH Calcium Phosphorus
10 Hyper PTH Adenoma
20 Hyper PTH CKD
30 Hyper PTH long standing
20 Hyper PTH
behaves like
Adenoma

38. TERTIARY HYPERPARATHYROIDISM
• B) S.calcium + S.phosphorus
30 Hyper PTH PTH > 1000
Cinacalcet 30mg HS
if no response - Parathyroidectomy

39. • INDICATIONS FOR PARATHYROIDECTOMY
1) severe hypercalcemia / 30 Hyper PTH
non responsive to drugs.
2) severe extraskeletal calcification/ calcific
uraemic arteriopathy.
3) resistant pruritis.

40. VASCULAR CALCIFICATION
• Two types:-
• Intimal : related to atherosclerosis ( very patchy).
• Medial : dependent on PTH and calcium and phosphorus.
- Results in loss of arterial distensibility,
- decrease in coronary perfusion.
- LVH, diastolic or systolic dysfunction.

41. • CKD patients ingested calcium can not be incorporated in to
bones and therfore gets deposited in extraosseous sites i.e
vascular bed and soft tissues .
• the magnitude of calcification is propotional to age ,
hyperphosphatemia, low PTH levels and low turn over
disease.
calcifications in media of coronary arteries and even in heart
valves.
increased CVS mortality

42. • Diagnoses made by
- Xray - ABD - lateral view.
- CT- ABD.
- Electron- beam CT.

43. • Optimal PTH levels in CKD are not known, but because
skeletal resistance to PTH develops with uraemia, relatively
high levels are targetted in CKD to avoid Adynamic Bone
Disease.
• Expert guidelines suggest goal PTH levels near or just above
the upper limit of normal for for moderate CKD, and
atleast twofold and up to ninefold the upper limit of normal
for ESKD.

44. THANK YOU