CKD MBD

Question 1

What is the effect of FGF-23 on phosphorus?

Answer 1

• Binds FGFR (and its co-factor, Klotho) in the proximal renal tubular cells to cause down regulation of NPT IIa and IIc. This leads to reduced reabsorption and phosphaturia
• Decreases Calcitriol synthesis by inhibiting 1-a-hydroxylase in the kidney
• This second action results in reduced intestinal absorption of PO43-.

Question 2

What is the effect of giving Ca IV to a patient with hypoparathyroidism?

Answer 2

They develop hypercalciuria as there is no PTH to promote Ca reabsorption

Question 3

What would you expect the PTH to be in hypercalcaemia secondary to hyperthyroidism?

Answer 3

Low

Question 4

What occurs in CKD patients (non-dialysis) who are prescribed cinacalcet?

Answer 4

They become hypocalcaemic and hyperphosphataemic. However, cinacalcet is used post transplant for HPTH.

Question 5

There is good evidence for the use of phosphate binders in non-dialysis CKD. True/False

Answer 5

False. One study found an increased risk of vascular calcification when binders were given in this population.

Question 6

What is the target for phosphorous in CKD-MBD?

Answer 6

Aim to get the PO43- to within the normal range.

Question 7

How does FGF-23 induce phosphaturia?

Answer 7

By suppressing the expression of NPT2a and NPT2c in the proximal tubule.

Question 8

What are the chief regulators of FGF-23?

Answer 8

Increased by hyperphosphataemia and 1,25 OH Vit D

Question 9

What are the associations with an elevated FGF-23?

Answer 9

1. Increased mortality in critically ill patients
2. LVH and heart failure
3. Anaemia
4. Osteoporosis

Question 10

What are the causes for pseudohypocalcaemia?

Answer 10

1. acute respiratory alkalosis
2. severe metabolic alkalosis
3. Hypoalbuminaemia

Question 11

What is the action of klotho?

Answer 11

Co-factor of FGF-23, helps in bind and activate its receptor, FGFR1. Decreased levels of klotho are observed early in CKD and may account for the reduced phophaturia that is observed (despite an elevated FGF-23).

Question 12

What is the effect of VDRA on FGF-23 levels?

Answer 12

They cause them to increase

Question 13

How does cinacalcet exert its action?

Answer 13

Cinacalcet acts on the CaSR as a positive allosteric modulator thereby increasing sensitivity of the parathyroid gland to calcium. This results in reduced release of PTH.

Question 14

What does Cochrane say about survival benefit with cinacalcet?

Answer 14

Although EVOLVE suggested a survival benefit in patients treated with cinacalcet, Cochrane found no such benefit.

EVOLVE suggested a benefit in terms of cardiovascular mortality in patients on haemodiaylsis over the age of 65

EVOLVE also demonstrated a reduced risk of fracture among haemodialysis patients over 65 years.

Question 15

What is the principle difference between cinacalcet and etecalcitide?

Answer 15

Cinacalcet acts on the CaSR as a positive allosteric modulator (i.e. it indirectly causes a reduction in PTH by improving the sensitivity of PT cells to EC calcium); Etecalcitide is a direct CaSR agonist.

Question 16

What are the incontrovertible benefits of cinacalcet?

Answer 16

(1) Reduced fracture risk
(2) Reduced hospitalisation
(3) Reduced need for parathyroidectomy

Question 17

What is the recommended calcium intake for patients with CKD?

Answer 17

1000mg/d

Question 18

By what mechanism does IV iron cause hypophosphatemia?

Answer 18

It is thought that hypophos with IV iron occurs secondary to increases in serum FGF-23 concentrations. This leads to reduced expression of NPT2a and NPT2c in the proximal tubule.

Question 19

What disease results from a mutation in NPT2c?

Answer 19

Hereditary hypophosphataemia with rickets and hypercalciuria.

Question 20

What disease results from a mutation in NPT2a?

Answer 20

AR Fanconi Syndrome with Rickets and Hypophosphataemic kidney failure.

Question 21

What is the aetiology of hypophosphataemia post transplant?

Answer 21

It is believed to occur primarily on account of persistently elevated levels of FGF-23. If it persists beyond one year, persistent MBD (SHPTH) is likely.

Question 22

What drugs are associated with hypophos?

Answer 22

TKI (sutent, imatinib), steroids, diuretics, IV glucose (causes an intracellular shift)

Question 23

What electrolyte abnormality is sometimes observed post liver resection?

Answer 23

Hypophosphataemia. Thought to occur secondary to increased expression of NAMPT in the proximal tubule; this reduces the expression of Na and PO43- cotransporters.

Question 24

What is the cause for FHH?

Answer 24

AD, loss of function mutation in CaSR.

Question 25

What mutations lead to elevated FGF23 and hypophosphataemia?

Answer 25

AD hypophosphataemic rickets(HR) - mutations in FGF-23 that renders FGF23 resistant to degradation

AR HR- mutations in DMP-1 (a molecule which normally suppresses FGF23 release from bone.)

X-linked HR- mutation in PHEX, again believed to play a role in the degradation of FGF23.

Question 26

What are the causes of hypermagnesamia?

Answer 26

Kidney failure with excess intake
Rhabdomyolysis
Redistribution in acute acidosis
FHH
DKA
Milk alkali
Theophylline toxicity
Adrenal insufficieny
Hypothyroidism
Lithium

Question 27

What is the treatment of hypermagnesaemia?

Answer 27

Give IV Ca2+ (100-200mg)

Question 28

A mutation in Claudin 16/19 in the TAL leads to what specific condition?

Answer 28

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis

Question 29

A mutation in HNF1B leads to what phenotype?

Answer 29

Renal cysts, diabetes, renal magnesium wasting and hypocalciuria.

Question 30

How do CNI cause hypomagnesaemia?

Answer 30

They reduce renal TRMP6 expression in the DCT.

Question 31

What are the clinical clues to ABD?

Answer 31

• Hypercalcaemia
• Hypophosphataemia
• Low iPTH