El Sahel Conference

1. The Inconspicuous Side of
Hyperparathyroidism
Wael Nassar, MBBch, MSc, FA (Germ.), MD.
Consultant of Internal Medicine & Nephrology.
October Six University; Sahel Teaching Hospital.
Cairo, Egypt

2. Key Topics
* Calcium load
* Vascular Calcification

3. Important questions
Is optimization of Ca, PO4, PTH, and D3 is enough ?
Is Vascular calcification an active or passive process ?
When should we start treatment of hyperparathyroidism ?

4. Enemies & Weapons of CKD patients
Enemies :
Hyperparathyroidism
Hyperphosphatemia
Hypocalcemia
Hypovitaminosis D
Increased FGF23
Decreased klotho
Weapons :
Nutritional vitamin D
VDRA
Calcimimitics (Mimpara)
Ca-containing PO4 binders
Non-Ca containing PO4 binders
Surgery
FGF-23 is a counter-regulatory hormone for vitamin D.
Klotho functions as a cofactor for the stimulation of the FGF-23 receptor.

5. Previous Present
Push PTH as low as possible!
Well, not that low, and assays
are not perfect
Give as much activated vitamin
D as possible
Well, not that much (and change
vitamin D type)
Give lots of calcium to suppress
PTH
Too much calcium can cause
calcium overload and vascular
calcification
A phosphorus of 7 and calcium
× phosphorus of 70 is okay
But that can cause vascular
calcification and is associated
with mortality
25(OH)-vitamin D is not
important
Deficiency is common

8. Markers of mineral metabolism and mortality in a European haemodialysis
population,
Jürgen Floege et al, Nephrol Dial Transplant (2011)

9. Markers of mineral metabolism and mortality in a European haemodialysis
population,
Jürgen Floege et al, Nephrol Dial Transplant (2011)

10. Markers of mineral metabolism and mortality in a European haemodialysis
population,
Jürgen Floege et al, Nephrol Dial Transplant (2011)

11. Markers of mineral metabolism and mortality in a European
haemodialysis population,
Jürgen Floege et al, Nephrol Dial Transplant (2011)

13. Regulation of PTH Secretion
PTH secretion increases steeply to a maximum value of
five times the basal rate of secretion as calcium
concentration
falls from normal to the range of 1.9–2.0 mmol/L (7.5–
8.0 mg/dL) (measured as total calcium).

21. One mg increase in serum calcium or
phosphate confer the same risk of vascular
calcifications as nearly 2.5 years (28.8
months or > 5 years ( 63.5 months) of
treatment with hemodialysis respectively.
(BlocK GA et at J Am Soc Nephrol 2004 ; 15:2208-2218)

23. What is calcium load?
An Increase of serum ionized calcium.

39. -Vascular calcification traditionally has been
considered a passive precipitate process, but is
now thought to be an active cell-mediated process
resembling osteogenesis.

45. American Chemical Society, Nano 2016, 10, 3886−3899

47. -"Gli1 positive cells trans-differentiate and end up
resembling osteoblasts, secreting bone in the vessel
wall. During kidney failure, blood pressure is high
and toxins build up in the blood, promoting
inflammation.“
(Benjamin D. Humphreys, 2016)

48. Carotid artery calcifications, hematoxylin and eosin staining. A: Sheet-like
calcifications; B: Osteocytes are visible within the bone lacunae-like mature
structure in development with lamellar bone. L: Lumen; FC: Fibrous cap; Arrowhead:
Ossification; O: Osteocytes.
(Francesco Vasuri et al, World J Stem Cells 2014)

49. Osteoclasts-like giant cells admixed with inflammatory infiltrate. Arrows point
osteoblast cells.
(Francesco Vasuri et al, World J Stem Cells 2014)

50. Gli1+ stem cells (in red) deposit calcium in the arteries, increasing the risk of
atherosclerosis in patients with chronic kidney disease. (Image: Humphreys lab. 2016)
(Benjamin D. Humphreys, 2016)

51. These vascular progenitor cells may be trying to
perform their healing role in responding to injury
signals, but the toxic, inflammatory environment
somehow misguides their differentiation into the
wrong cell type.
(Benjamin D. Humphreys, 2016)

52. Genetic ablation of Gli1+ cells before CKD induction
in the mice "abolished vascular calcification (and)
suggests that adventitial Gli1+ cells are a major
source of osteoblast-like cells in the vascular wall and
an important source of vascular calcification in CKD.“
(Benjamin D. Humphreys, 2016)

56. Important questions
Is optimization of Ca, PO4, PTH, and D3 is enough ?
Is Vascular calcification an active or passive process ?
When should we start treatment of hyperparathyroidism ?

58. Conclusions
-Vascular calcification is the main cause of cardiovascular
Complications and mortality associate chronic renal failure.
- Calcium balance is important. We should not allow
neither negative calcium load for fear of metabolic
bone disease nor Positive calcium load for fear of vascular
calcification.
- Low dialysate calcium is important (< 1.25 mmol).
- Serum ionized calcium and not total serum calcium.
- Proper hemodialysis dose to keep HCO3 > 18 and Base
Deficit < 6 in between HDx. sessions.
- Treatment of hyperparathyriodism should start early
enough(CKD 3-4).

60. THANK YOU