Ckd mbd - dr. hanan moustafa

1. HANAN MOSTAFA
NEPHROLOGY SPECIALIST
CKD-MBD

2.  Definitions.
 Pathogenesis.
 Clinical Features.
 Investigations.
 Laboratory Target Levels.
 Treatment.

3. Abnormalities of calcium, phosphorus, PTH, or
vitamin D metabolism.
Abnormalities in bone turnover, mineralization,
volume, linear growth, or strength.
Vascular or other soft tissue calcification.
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4. Beginning in CKD stage 3, the
ability of the kidneys to excrete
a phosphate load is diminished,
leading to hyperphosphatemia,
elevated PTH, and decreased
1,25(OH)2D with associated
elevation of FGF-23.

8. There is a number of feedback loops between the
kidney, bone, intestine, parathyroid glands and the
vasculature.
The main abnormalities in SHPT are:
- PO4 retention. - Decreased iCa.
- Decreased calcitriol. - Increased FGF-23.
- Reduced expression of vitamin D receptors (VDRs),
calcium-sensing receptors (CaSRs), FGF receptors,
and klotho in the parathyroid glands.

9. FGF-23 is a circulating peptide, secreted by bone
osteocytes and osteoblasts in response to calcitriol,
increased dietary phosphate load, PTH, and calcium.
Klotho, a transmembrane protein produced by
osteocytes, is required for FGF-23 receptor activation.
Inadequate response to PTH, which normally promotes
phosphaturia and calcium reabsorption, or to FGF-23,
which also enhances phosphate excretion.

10. Initial compensatory mechanisms, including increase
PTH and FGF-23 and temporarily increase PO4 levels,
reduce PO4 reabsorption and thus maintain PO4
levels in normal to near-normal range.
However, hyperphosphataemia usually occurs in the
later stages of CKD, when dietary intake of phosphate
exceeds the rate of renal excretion.
There is an association between higher serum
phosphate and mortality in CKD patients.

11. Tertiary hyperparathyroidism : autonomous
secretion of PTH that is no longer adequately
responsive to the plasma calcium concentration.
Decreased expression of CaSR and VDRs results
in a lack of suppression of PTH by increasing
calcium or vitamin D analogs.
Nodular parathyroid glands do not undergo
involution, despite resolution of some of the
triggering mechanisms.

12. Phosphate homeostasis

18. Osteitis fibrosa: increased osteoclast & osteoblast
activity, peritrabecular fibrosis, and increased bone
turnover.
 Osteomalacia: defective mineralization of newly
formed osteoid most often caused by aluminum
deposition; bone turnover is decreased.
 Adynamic bone disease : abnormally low bone
turnover.
Osteopenia or osteoporosis.
 Mixed renal osteodystrophy.
Others (e.g., chronic acidosis, β2-microglobulin
amyloidosis).

21. Calciphylaxis (Calcific uremic arteriolopathy) is
a rare and serious disorder characterized by
systemic medial calcification of the arterioles that
leads to ischemia and subcutaneous necrosis.

22. Bone Disease:
Most cases are asymptomatic
Weakness, fractures, bone and muscle pain.
Tendon rupture
Avascular necrosis (especially in dialysis).
Extra skeletal Calcifications:
Vascular calcification: systolic hypertension, left
ventricular hypertrophy , and impaired coronary
artery perfusion.
Soft tissue calcification.

23. Cardiovascular Mortality in the General Population and in
Dialysis Patients

24. Lab.:
- iPTH, S. Ca, S.po4, Alp, 25(OH)D.

25. Radiology:
- Echo, Lateral Abdominal & Bone Radiographe.

28. Stage of CKD S.Ca S.Po4 iPTH Ca x Po4
3
Normal 2.7-4.6
35-70
>554 70-110
5-5D 8.4-9.5 3.5-5.5 150-300
Parathyroid hormone levels
In CKD 5D it is recommended to maintain PTH level in the range of
approximately 2-9 times the upper limit of normal for the assay (KDIGO).

29. 2nd
hyperPTH and hyperphosphataemia
1.Dietary phosphorous restriction.
2. Phosphate binders.
3. Calcitriol or other Vit D analogues.
4. Calcimimetics.
5. Parathyroidectomy.

31. Dietary restriction
•Restrict dietary phosphate intake to 900 mg/day .
•Should be derived from sources of high
biologic value, such as meats and eggs.
Phosphate binders
•Ca containing.
•Non Ca containing.

32. - Used in hypocalcemic or normocalcemic patients with
no evidence of vascular calcification.
- The amount of elemental calcium contained in the
phosphate binder should not exceed 1500 mg per day .
- chewed with food to maximize binding of ingested
phosphorous.
- Calcium carbonate & calcium acetate are extensively
used today.
• Ca containing phosphate binders:

33. • Non Ca containing phosphate binders:
- Used in hypercalcemic patients &patients with adynamic
bone disease or vascular calcification.
- In the 1970s, aluminium represented the mainstay of
phosphate-binding therapy; this treatment was largely
abandoned when cases of systemic aluminium toxicity
arose.
- Sevelamer was initially available as sevelamer HCl.
- However, sevelamer HCl was associated with reduced
serum bicarbonate concentration&metabolic acidosis.
- Subsequently, a different formulation, sevelamer
carbonate, was developed.

35. Vitamin D, calcitriol, and vitamin D analogs
• Vitamin D includes both vitamin D2 (ergocalciferol) and vitamin
D3 (cholecalciferol).
• Vitamin D derivatives include:
1. the naturally occurring vitamin D metabolite, calcitriol (1,25-
dihydroxycholecalciferol [1,25(OH)2D]).
2. synthetic vitamin D analogs such as doxercalciferol, paricalcitol,
alfacalcidol, falecalcitriol, and 22-oxacalcitriol (or maxacalcitol [1,25
dihydroxy-22-oxavitamin D3]).
•1,25-(OH)2 Vitamin D3 or other analogues bind to receptor on
Parathyroid tissue and suppress PTH production.

36. Vitamin D, calcitriol, and vitamin D analogs
•Most dialysis patients with increased plasma iPTH
levels (>300 pg /mL) require treatment with calcitriol or
vitamin D analogs.
• Because calcitriol increases gastrointestinal
absorption of calcium and phosphate, more selective
vitamin D analogs have been developed that may
reduce the risk of hypercalcemia and
hyperphosphatemia.

37. Vitamin D, calcitriol, and vitamin D analogs
•The optimal dose of calcitriol or synthetic vitamin D
analogs has not been established and depends upon
the concurrent use of calcimimetics, the dose of
concomitant calcium based phosphate binders, and the
potency/selectivity of the vitamin D analog.
• The current approach has been empiric, with the
goal of administering increasing doses of vitamin D
analogs, along with phosphate binders, to achieve
target plasma levels of Ca, PO4 and PTH.

38. Vitamin D, calcitriol, and vitamin D analogs
•The continued up-titration with active vitamin D to
supraphysiologic levels, if necessary to suppress PTH,
is often successful in lowering PTH, but frequently
achieves this one goal at the expense of
hypercalcemia and hyperphosphatemia.
•The effect of oral pulse alfacalcidol is superior to its daily
use in the treatment of 2nd
hyperparathyroidism.
•The efficacy of oral alfacalcidol is similar to that of IV in
managing 2nd
hyperparathyroidism.

39. Vitamin D, calcitriol, and vitamin D analogs
•In general, the dose of calcitriol or synthetic vitamin
D analogs should be reduced by 50% or stopped with
plasma calcium levels at the upper normal range or
with mild hypercalcemia (between 9.5 and 10.2 mg/dL).
• Calcitriol or the synthetic analog should be
discontinued for frank hypercalcemia (>10.2 mg/dL).

40. Vitamin D, calcitriol, and vitamin D analogs
Contraindications
• Calcitriol or synthetic vitamin D analogs should not
be given until the serum phosphorus concentration has
been controlled (<5.5 mg/dL) and the serum calcium is
<9.5 mg/dL.
• Low plasma PTH concentration, possibly <150pg/mL,
because of the association with adynamic bone d sease.

41. Vitamin D, calcitriol, and vitamin D analogs
Resistance
•Many patients with severe hyperparathyroidism show
little or no decline in plasma PTH levels with calcitriol
therapy .
•Limiting factors include:
1. Large functioning gland mass with nodular
hyperplasia (marked reduction in calcitriol receptors ).
2. Altered calcium sensitivity of parathyroid cells, and
3. Failure of high-dose vitamin D derivatives because
of hypercalcemia and/or hyperphosphatemia.

42. Calcimimetics
• Calcimimetics increase the sensitivity of the calcium-
sensing receptor (CaSR) in the parathyroid gland to
calcium, regulating PTH secretion and the gland
hyperplasia.
Dose: initiated at a dose of 30 mg/day, with stepwise
increments (increased every four weeks until goals are
achieved) to 60, 90, and 180 mg/day .
• Contraindications: Cinacalcet should not be started if
serum calcium is <8.4 mg/dL.

44. Adynamic Bone Disease (ABD)
1. Decreasing the doses of calcium-based phosphate
Binders.
2. Using non-calcium-based phosphate binders.
3. Decreasing or stopping active vitamin D analogs.
4. For patients on dialysis, possibly by using a low
dialysate calcium concentration.