Chronic kidney disease associated mineral bone disorders breif.

2.  Introduction
 Pathogenesis.
 Renal osteodystrophy
 Treatment Goals
 Laboratory Target Levels.
 Overview of Treatment of CKD-MBD.
 Conclusion

3.  Chronic kidney disease-Mineral & Bone
disorder (CKD-MBD) is one of the many
complications associated with chronic kidney
disease.
 It represents a systemic disorder of mineral
& bone metabolism due to CKD .

4.  It is manifested by either one or a combination
of the following:
 Abnormalities of calcium, phosphorus
(phosphate), PTH or Vit-D metabolism.
 Abnormalities in Bone turnover. Mineralization,
Volume, liner growth, or strength.
 Vascular or other soft-tissue calcification.

5.  As kidney function declines in chronic kidney
disease (CKD), there is a progressive
deterioration in mineral homeostasis, with a
disruption of normal serum and tissue
concentrations of phosphorus and calcium,
and changes in circulating levels of
hormones.

6. These include:
 Parathyroid hormone (PTH)
 25- hydroxyvitamin D (25(OH)D)
 1,25-dihydroxyvitamin D (1,25(OH)2D)
 Fibroblast growth factor-23 (FGF-23),
 Growth hormone.

7.  Beginning in CKD stage 3, the ability of the
kidneys to appropriately excrete a phosphate
load is diminished, leading to:
 Hyperphosphatemia,
 Elevated PTH,
 Decreased 1,25(OH)2VitD
 With associated elevations in the levels of
FGF-23.

8.  Kidney fails to respond adequately to
PTH, which normally promotes
phosphaturia and calcium reabsorption, or
to FGF-23, which also enhances
phosphate excretion.

9. Renal osteodystrophy is defined as:
“ An alteration of bone morphology in patients
with CKD”.
o It is one measure of the skeletal component of
the systemic disorder of CKD–MBD.

10.  It is metabolic bone disease that consists of:
 Hyperparathyroid bone disease(Osteitis
fibrosa)
 Osteomalacia
 Osteoporosis
 Osteoscelerosis

11.  It is defined as:
“Osteitis fibrosa is a complication of
hyperparathyroidism ,a condition in which
certain bones becomes abnormally weak
and deformed”.

12.  PATHOPHYSIOLOGY IN RELATION TO CKD:
 It is a common presentation of renal osteodystrophy, which is
a term used to refer to the skeletal complications of ESRD.
 OF occurs in approx 50% of pts wd ESRD.
 ESRD occurs when the kidneys fails to produce calcitriol, a
form of Vit-D, which assists in absoption of Ca into the bones.
 When calcitriol levels dec, PTH levels inc, halting the storage
of Ca & instead triggering its removal from the bones.

13.  SIGNS & SYMPTOMS:
 Bone pain or tenderness
 Bone Fxs
 Skeletal deformalities such as bowing of legs
 Underlying hyperparathyroidism may cause:
 Kidney stones
 Nausea
 Constipation
 Fatigue & weakness
 Fxs are most commonly localized in the arms,
legs or spine.

14.  DIAGNOSIS:
 Blood Tests:
 High levels of Ca (normal b/w 8.5 & 10.2 mg/dl)
 Inc PTH levels
 Inc alk phosphatase.
 On X-Rays:
 Extremely thin bones(often bowed or fractured)
 Lytic & multilobular cystic changes.

16.  MANAGEMENT:
 Medical :
 Intravenous Vit-D
 Surgical:
 In especially severe cases parathyroidectomy
or the full removal of parathyroid glands.

17. “ In osteomalacia , there is a normal
amount of bone but its mineral content is
low (there is excess uncalcified osteoid
and cartilage”.
 It is characterized by low
bone turn-over in combination
with abnormal mineralization.

18.  PATHOGENESIS IN RELATION TO CKD:
 Renal failure leads to 1,25
hydrooxycholicalciferol deficiency.
 Low levels of 1,25(HO)2Vit-D causes dec Ca
absorption from the intestine leading to
Hyocalcemia.
 So dec bone mineralization i.e reduction in
the calcification of osteiod in bones.

19.  SIGNS AND SYMPTOMS:
 Diffuse joints & Bone pain & tenderness
 Fxs (esp femoral neck)
 Muscle weakness
 Difficulty walking often with waddling gait

20.  INVESTIGATIONS:
 Blood Tests:
 dec Ca
 Dec PO4 except in cases of renal
osteodystrophy
 Inc serum Alk Phosp(due to an inc in
compensatory osteoblast activity)
 Inc PTH levels( due to low Ca)

21.  X-Rays:
 There is loss of cortical bone; also apparent
partial Fxs, without displacement may be seen .
 Pseudofractures also called “ Looser’s zones”.
 Biopsy:
 Bone Bx shows incomplete mineralization.

23.  TREATMENT:
 1-alpha-hydroxylated Vit-D.
 Dietary restriction of foods with high
phosphate content.
 Phosphate binding drugs (calcium
carbonate, aluminum hydroxide).

24. “Osteoporosis, means porous bone, it is
desease in which the density & quality of
bone are reduced. As bones become
more porous & fragile, the risk of Fx is
greatly increased. The loss of bone
occurs silently & progressively”.
 Pts with CKD are more likely to develop osteoporosis &
Fxs than age-matched controls without kidney disease.

26.  PATHOPHYSIOLOGY IN RELATION TO
CKD:
 Ca deficiency can lead to sec
hyperparathyroidism, which inc Ca
resorption from bone, dec renal Ca excretion
& inc renal production of 1,25-di(OH)2Vit-D.
 Also, Vit-D def results in sec
hyperparathyroidism via dec intestinal Ca
absorption.

27.  SYMPTOMS & SIGNS:
 Bone pain or tenderness
 Fxs with little or no trauma
 Loss of height over time
 Neck or lower back pain due to Fxs
 Stooped posture

28.  INVESTIGATIONS:
 X-ray (cortical thining & inc radiolucency)
 DEXA-scan( Dual Energy X-Ray)
 Levels of Ca, PO4 & alk phos levels in blood.

30. Osteoscelerosis is defined as:
“It is a disorder that characterized by
abnormal hardening of bone and an
elevation in bone density. It is
predominantly affect the medullary
portion &/or cortex of bone”.

31.  PATHOPHYSIOLOGY IN RELATION TO CKD:
 Osteoscelerosis can occur in sec
hyperparathyoidism.
 Such changes are frequently found despite the
presence & predominanace of resorption.
 They are related either to excessive osteoblastic
cell function in response to bone resorption or to inc
production of mineralized osteiod.

33.  CALCIUM & PHOSPHORUS LEVELS:
For those with stage 3 & 4 CKD, the following treatment goals were
recommended:
o Serum level of phosphorus should be maintained between 2.7
mg/dL - 4.6 mg/dL.
o The serum levels of corrected total calcium should be
maintained within the "normal" range for the laboratory used
o The serum calcium-phosphorus product should be maintained at
<55 mg2/dL2

34. For those with stage 5 & 5D CKD, the following are
recommended:
o Serum levels of phosphate should be maintained
between 3.5 and 5.5 mg/dL
o Serum levels of corrected total calcium should be
maintained between 8.4 and 9.5 mg/dL
o The serum calcium-phosphate product should be
maintained at <55 mg2/dL2

35.  PARATHYROID HORMONE LEVELS:
o Stage 3 CKD: 35 to 70 pg/mL.
o Stage 4 CKD: 70 to 110 pg/mL.
o Stage 5 & 5D CKD: 150 to 300 pg/mL

36.  Dietary phosphate restriction and phosphate
binders.
 Vitamin D, calcitriol, and vitamin D analogs.
 Calcimimetics.
 If necessary , surgery surgery can improve
the body’s ability to repair bones damaged
by mineral & bone disorder in CKD.

37. S T O P

41.  INDICATIONS OF SURGERY:
 ESRD patients who have markedly elevated and medical therapy-
refractory PTH levels and related signs and symptoms are generally
referred for parathyroidectomy.
 Parathyroidectomy should not be performed unless high PTH levels
(>800 pg/mL) have been documented.
 The following signs and symptoms warrant parathyroidectomy in the
setting of elevated PTH values in the absence of another known
etiology:
 Severe hypercalcemia
 Progressive and debilitating hyperparathyroid bone disease
 Refractory pruritus
 Progressive extraskeletal calcification or calciphylaxis
 Otherwise unexplained myopathy

42.  Measuring serum levels of Ca, PO4, PTH, Vit-D
& Alk Phos activity in the CKD stage 3b-5.
 Early intervention to correct abnormal Ca & P
metabolism are important to reduce
cardiovascular mortality and morbidity.
 Normalization of P/Ca & optimal PTH level &
dietary PO4 restriction & its binder dosage.
 usually need paricalcitol & cinacalcet in CKD
stage 5D.