Ckd

1. Chronic Kidney Disease-
Mineral Bone Disorders
Kamal Mohamed Okasha MD.
Prof of Nephrology, Tanta Uinversity
ISN Sistership Renal Program with Sheffield instite.

5. Definition of CKD-Mineral and Bone Disorder
A systemic disorder of mineral and bone metabolism due to
CKD manifested by either one or a combination of the
following:
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
Moe S, et al. Kidney Int 69: 1945, 2006

6. Definition of Renal Osteodystrophy
Renal osteodystrophy is an alteration of bone
morphology in patients with CKD.
It is one measure of the skeletal component of the
systemic disorder of CKD-MBD that is quantifiable
by histomorphometry of bone biopsy.
Moe S, et al. Kidney Int 69: 1945, 2006

7. Chronic Kidney Disease-Related Mineral and Bone
Disorder: Public Health Problem. Kerry Willis PhD
National Kidney Foundation

8. Secondary hyperparathyroidism encompasses most of the
biochemical abnormalities that characterize CKD-MBD.
Causes of secondary hyperparathyroidism:
Phosphate retention.
Decreased free calcium concentration.
Decreased 1,25-dihydroxyvitamin D (calcitriol) concentration.
Reduced expression of vitamin D receptors (VDRs).
Calcium-sensing receptors (CaSR).
Fibroblast growth factor receptors (FGFRs), and klotho in the
parathyroid glands.

10. Characteristics of the major CKD-related bone
diseases:
 Osteitis fibrosa cystica
Adynamic bone disease
Osteomalacia
Mixed uremic osteodystrophy

11. Case 1
• Mr SM is a 53-year-old man with end-stage renal disease
(ESRD) secondary to type 2 diabetes.
• He also has hypertension and hypercholesterolemia. His
medications include insulin, an antihypertensive, and a
cholesterol-lowering agent.
• He has recently begun hemodialysis. He quit smoking
cigarettes 1 year ago; he had a 30-year pack/day history.
• He is a retired high school teacher.
• His physical activity is limited to indoor.

12. • Which of the following is most likely to be true regarding Mr SM
serum calcium and phosphorus levels?
1. Both his serum phosphorus and serum calcium levels will be above
the normal laboratory range
2. Both his serum phosphorus and serum calcium levels will be below
the normal laboratory range
3. His serum phosphorus level will be above the normal laboratory
range and his serum calcium level will be below the normal
laboratory range
4. His serum phosphorus level will be above the normal laboratory
range and his serum calcium level will be within the normal
laboratory range

13. • Available data demonstrate that among individuals with stage
5D CKD (stage 5 CKD on dialysis) serum calcium levels remain
in the normal range and serum phosphorus levels are
elevated.
• Results were found when examining cross-sectional data from
the international Dialysis Outcomes and Practice Pattern Study
(DOPPS)

15. • Therefore: the correct answer is:
4. His serum phosphorus level will be above the normal
laboratory range and his serum calcium level will be within the
normal laboratory range

16. Patient Case 1 (cont)
• His calcium and phosphorus levels every 3 months and have
noted based on several measures that while his serum calcium
level is normal, his serum phosphorus level remains
persistently above the normal laboratory range.
• Which of the following would be the first step in trying to
lower Mr Smith's serum phosphorus level?
1. Increase the frequency of dialysis from 3 times to 5 times a
week
2. Increase the dialytic phosphate removal
3. Reduce phosphate intake through dietary modifications
4. Start a phosphate binder

17. • Adequate control of serum phosphorus is a cornerstone
in the clinical management of patients with CKD because
hyperphosphatemia contributes to the pathogenesis of
hyperparathyroidism, vascular calcification, and
increased cardiovascular mortality.
• Interventions include dietary phosphate restriction (first-
line), dialysis, and phosphate binders.
• So the correct answer is:
3. Reduce phosphate intake through dietary modifications
so dietary restriction of phosphorus – restricting the intake
of colas, legumes, and dairy products -- is the cornerstone
of management.

18. Patient Case 1 (cont)
• Despite dietary modifications aimed to decrease phosphate
intake, serum phosphorus level remains elevated. He now
requires an intestinal phosphorus binder.
• Which of the following statements concerning use of a
phosphate binder in this patient is true?
1. Non-calcium-based binders are associated with a decrease
in mortality
2. Aluminum hydroxide is safe to use
3. Calcium salts have not been associated with any harm
4. Non-calcium-based binders have no advantage with respect
to hard clinical outcomes compared with calcium-based
binders

19. • Aluminum hydroxide is a potent phosphate binder but is
associated with skeletal, neurological, and hematological
toxicity.
• Calcium salts, specifically calcium carbonate and calcium
acetate, are effective in lowering serum phosphorus levels but
may cause harm.
• It appears that non-calcium-based phosphate binders are
associated with less progression of coronary artery
calcification and a decrease in mortality, likely due to a
decrease in CV deaths.
• Therefore the correct answer is:
1. Non-calcium-based binders are associated with a decrease
in mortality

20. Patient case 1
• Mr SM has now been on dialysis for 1 year.
• He is poorly compliant to low phosphorus diet and calcium
carbonate, he often skips doses.
• His laboratory testing consistently demonstrates a mild elevation in
his phosphorus level, a normal serum calcium level, and an elevated
serum intact parathyroid hormone (PTH) level.
• He is at risk for Vascular complication.
• Which of the following interventions would be inappropriate for
Mr SM?
1. Refer to a renal dietitian
2. Change from a calcium-based to a non-calcium-based binder
3. Obtain a lateral abdominal radiograph to assess for the presence
or absence of vascular calcification
4. Prescribe vitamin K to prevent calcification

21. • The prevalence of vascular calcification increases as kidney
function declines.
• Vitamin K (through its effects on matrix Gla protein) may
inhibit the progression of vascular calcification.
• Individuals with ESRD commonly have a vitamin K deficiency.
• Of note, while there are 3 randomized controlled trials
currently recruiting individuals with CKD to evaluate the
effects vitamin K on vascular calcification.
• To date there are no data showing that correcting a vitamin K
deficiency prevents or improves vascular health in CKD.
• As a result, clinical practice guidelines such as those from
KDIGO do not recommend routine vitamin K supplementation
in individuals with kidney disease.

22. • Therefore the correct answer is :
4. Prescribe vitamin K to prevent calcification would be
inappropriate for Mr SM?

23. Case 2
• Ms L S is a 29-year-old woman with recently diagnosed lupus
nephritis.
• She is referred to you for management of her stage 3 CKD
(estimated glomerular filtration rate [eGFR]= 35 mL/min).
• She is asymptomatic with regard to her lupus.
• She does not smoke and attends excercise twice each week.
• She is married with a 7-year-old child.

24. Case 2
• Which of the following is most likely to be TRUE regarding
Ms LS serum phosphorus level?
• Her serum phosphorus level will be above the normal
laboratory range
• There are no data showing that elevated serum phosphorus
levels are associated with any adverse events
• Her serum phosphorus level will be below the normal
laboratory range
• The lower you can get her serum phosphorus level, the lower
the prevalence of adverse events in this patient

25. The prevalence of abnormalities in serum phosphorus has been
described using cross-sectional data in 1800 individuals with
stages 3 to 5 CKD. once eGFR declines to less than 40 mL/min –
her eGFR is 35 mL/min -- then serum phosphorus rises.

26. • Hyperphosphatemia is an inevitable consequence of
decreasing renal function.
• Therefore the correct answer is:
1. Her serum phosphorus level will be above the normal
laboratory range

27. • Which of the following statements about Ms West's serum
calcium is most likely correct?
1. Her serum calcium level will be below the normal laboratory
range
2. Her serum calcium level will be within the normal laboratory
range
3. There are no clinical consequences associated with an
elevated serum calcium level
4. Her serum calcium level will be above the normal laboratory
range

28. • The same cross-sectional study also described the prevalence
of abnormalities in serum calcium according to stage of CKD
• Note that the prevalence of hypocalcemia that increases with
declining renal function is exceedingly low -- at most 15% with
an EGFR lower than 20 mL/min.

29. • The presence of an abnormal calcium level is unlikely at this
stage of kidney disease
• So the correct answer is :
2. Her serum calcium level will be within the normal laboratory
range

30. Case 2
Laboratory testing demonstrates a serum calcium level of 2.50
mmol/L (within normal laboratory range), a serum phosphorus
level of 1.8 mmol/L (above the normal laboratory range), and a
PTH of 10.3 pmol/L (above the normal laboratory range).
• Based on these laboratory results, which of the following
statements is FALSE regarding the next appropriate step for
Ms West?
1. Dietary restriction of serum phosphorus would be beneficial
2. In the early stages of CKD dietary restriction of phosphorus
may be all that is required
3. Phosphate binders (calcium-based and/or non-calcium-
based) have no role in the management of
hyperphosphatemia in predialysis CKD
4. Calcium salts are effective phosphate binders

31. • phosphate binders and a phosphorus-restricted diet can be
considered in patients with CKD to help keep serum
phosphorus levels within the normal range.

32. All-cause mortality for each type of phosphate
binder

33. • So the correct answer is:
3. Phosphate binders (calcium-based and/or non-calcium-
based) have no role in the management of hyperphosphatemia
in predialysis CKD

34. Case 3
• 42-year-old man who has advanced focal segmental
glomerulosclerosis and an estimated glomerular filtration rate
(eGFR) of 18 ml/min/1.73m2.
• His past medical history includes hypertension and osteoarthritis. He
does not smoke or drink alcohol excessively.
• Current medications include lisinopril 20 mg daily, amlodipine 10 mg
daily, and fish oil.
• A previous 6-month trial of high-dose corticosteroids failed to
impact the course of his disease and was discontinued.
• He plans to receive a living donor kidney from his sister when he
reaches end-stage renal disease.
• He denies uremic symptoms, including dyspnea, fatigue, anorexia,
nausea, pruritus, or swelling.
• His exam reveals a body mass index of 27 kg/m2, blood pressure of
147/85 mm Hg, and trace pedal edema.
• His serum albumin level is 3.6 g/dL

35. Serum calcium 7.8 mg/dL
(normal range 8.4 to
10.2 mg/dL)
Serum phosphate 4.0 mg/dL
(normal range 2.5 to 4.5
mg/dL)
Serum parathyroid
hormone
241 pg/mL
(normal range 8 to 65
pg/mL)
Serum 25-
hydroxyvitamin D
32 ng/mL

36. • Which of the following is most likely to be responsible for
the patient's hypocalcemia and hyperparathyroidism?
1. Phosphate retention
2. Substrate vitamin D deficiency
3. Calcitriol deficiency
4. Parathyroid hormone related peptide
5. Osteoarthritis

38. • Chronic kidney disease leads to impaired phosphate excretion
and reduced synthesis of 1,25(OH)2D (calcitriol).
• Calcitriol deficiency causes reduced absorption of dietary
calcium with a fall in serum calcium concentrations and
secondary hyperparathyroidism.
• So the correct answer is :
3. Calcitriol deficiency

39. • Which of the following treatments for mineral metabolism
disorders would be most appropriate in this case?
• Oral calcitriol 0.25 μg daily
• Cholecalciferol 2,000 IU daily
• Ergocalciferol 50,000 IU weekly
• Calcium carbonate 1200 mg daily
• Diltiazem 360 mg daily

40. • Calcitriol, the hormonally active form of vitamin D3 will most
effectively affect this patient's reduced synthesis of
1,25(OH)2D and thereby correct his low calcium levels and
secondary hyperparathyroidism.
• Serum 25-hydroxyvitamin D is 32 ng/mL within normal.
• So the correct answer is:
• Oral calcitriol 0.25 μg daily

41. • You initiate treatment with oral calcitriol 0.25 μg per day.
Which of the following should be checked within the next 3
months?
1. Serum 25-hydroxyvitamin D
2. Serum magnesium
3. Serum parathyroid hormone
4. Urine fractional excretion of phosphate
5. Serum calcium and phosphate

42. • Calcitriol increases gastrointestinal absorption of calcium and
phosphate through different receptors. Increased levels of
these minerals can be noted hours to days after treatment
initiation.
• The correct answer:
5. Serum calcium and phosphate

43. Thank You