The inconspecuous side of hyerparathyroidism dr. wael nassar

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

Key Topics

* Calcium load

* Vascular Calcification

Important questionsIs optimization of Ca, PO4, PTH, and D3 is enough ?

Is Vascular calcification an active or passive process ?

When should we start treatment of hyperparathyroidism ?

Enemies & Weapons of CKD patientsEnemies :

HyperparathyroidismHyperphosphatemiaHypocalcemiaHypovitaminosis DIncreased FGF23Decreased klotho

Weapons :Nutritional vitamin DVDRACalcimimitics (Mimpara)Ca-containing PO4 bindersNon-Ca containing PO4 bindersSurgery

FGF-23 is a counter-regulatory hormone for vitamin D.Klotho functions as a cofactor for the stimulation of the FGF-23 receptor.

Previous PresentPush 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

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

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

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

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

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

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)

What is calcium load?

An Increase of serum ionized calcium.

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

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

-"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)

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

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

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)

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)

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)

Important questionsIs optimization of Ca, PO4, PTH, and D3 is enough ?

Is Vascular calcification an active or passive process ?

When should we start treatment of hyperparathyroidism ?

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).

THANK YOU