CKD MBD Flashcards
What is the effect of FGF-23 on phosphorus?
- 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-.
What is the effect of giving Ca IV to a patient with hypoparathyroidism?
They develop hypercalciuria as there is no PTH to promote Ca reabsorption
What would you expect the PTH to be in hypercalcaemia secondary to hyperthyroidism?
Low
What occurs in CKD patients (non-dialysis) who are prescribed cinacalcet?
They become hypocalcaemic and hyperphosphataemic. However, cinacalcet is used post transplant for HPTH.
There is good evidence for the use of phosphate binders in non-dialysis CKD. True/False
False. One study found an increased risk of vascular calcification when binders were given in this population.
What is the target for phosphorous in CKD-MBD?
Aim to get the PO43- to within the normal range.
How does FGF-23 induce phosphaturia?
By suppressing the expression of NPT2a and NPT2c in the proximal tubule.
What are the chief regulators of FGF-23?
Increased by hyperphosphataemia and 1,25 OH Vit D
What are the associations with an elevated FGF-23?
- Increased mortality in critically ill patients
- LVH and heart failure
- Anaemia
- Osteoporosis
What are the causes for pseudohypocalcaemia?
- acute respiratory alkalosis
- severe metabolic alkalosis
- Hypoalbuminaemia
What is the action of klotho?
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).
What is the effect of VDRA on FGF-23 levels?
They cause them to increase
How does cinacalcet exert its action?
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.
What does Cochrane say about survival benefit with cinacalcet?
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.
What is the principle difference between cinacalcet and etecalcitide?
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.
What are the incontrovertible benefits of cinacalcet?
(1) Reduced fracture risk
(2) Reduced hospitalisation
(3) Reduced need for parathyroidectomy
What is the recommended calcium intake for patients with CKD?
1000mg/d
By what mechanism does IV iron cause hypophosphatemia?
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.
What disease results from a mutation in NPT2c?
Hereditary hypophosphataemia with rickets and hypercalciuria.
What disease results from a mutation in NPT2a?
AR Fanconi Syndrome with Rickets and Hypophosphataemic kidney failure.
What is the aetiology of hypophosphataemia post transplant?
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.
What drugs are associated with hypophos?
TKI (sutent, imatinib), steroids, diuretics, IV glucose (causes an intracellular shift)
What electrolyte abnormality is sometimes observed post liver resection?
Hypophosphataemia. Thought to occur secondary to increased expression of NAMPT in the proximal tubule; this reduces the expression of Na and PO43- cotransporters.
What is the cause for FHH?
AD, loss of function mutation in CaSR.
What mutations lead to elevated FGF23 and hypophosphataemia?
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.
What are the causes of hypermagnesamia?
Kidney failure with excess intake Rhabdomyolysis Redistribution in acute acidosis FHH DKA Milk alkali Theophylline toxicity Adrenal insufficieny Hypothyroidism Lithium
What is the treatment of hypermagnesaemia?
Give IV Ca2+ (100-200mg)
A mutation in Claudin 16/19 in the TAL leads to what specific condition?
Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis
A mutation in HNF1B leads to what phenotype?
Renal cysts, diabetes, renal magnesium wasting and hypocalciuria.
How do CNI cause hypomagnesaemia?
They reduce renal TRMP6 expression in the DCT.
What are the clinical clues to ABD?
- Hypercalcaemia
- Hypophosphataemia
- Low iPTH
