Phosphorus handling in the kidney

Question 1

what percentage of phosphorus is protein bound?

Answer 1

10-15%

Question 2

what percentage of phosphorus is reabsorbed?

Answer 2

80-98%

Question 3

at what point is the normal phosphate reabsorption mechanism saturated? what happens after that? what’s that called, for short?

Answer 3

~3.5-4.0 mg/dL after which point all is excreted; Tmax-phos

Question 4

where does the vast majority of phosphorus reabsorption happen?

Answer 4

in the PCT

Question 5

what is known about reabsorption in the DCT?

Answer 5

not much

Question 6

what’s the mechanism by which phosphorus is reabsorbed?

Answer 6

Na/HPO4 cotransport driven by the electrical gradient (in the main form, which pumps in 3 Na for every one HPO4); and also by the Na concentration gradient (for both the electrical transporter and the electroneutral transporter) this is on the apical membrance, basolateral membrane transport not well understood

Question 7

what is the main form of phosphorus in the serum?

Answer 7

HPO4 - 2- (divalent) because pK of the HPO4 H2PO4 reaction is 6.8

Question 8

what are the two main types of phosphorus transporters in the PCT? what are their electrical relationships?

Answer 8

NaPi IIa - 90% - electrically charged (3Na)

NaPi IIc - 10% - electroneutral (2Na)

Question 9

what is the name of the transporter for phosphorus in the intestine? what is different about it from the ones in the kidneys?

Answer 9

NaPi IIb; it doesn’t have two amino acid residues, KR around the C-terminus that are required for binding to PTH

Question 10

what are the NaPi type III transporters that are located in the kidney? what makes them different from the type II transporters?

Answer 10

PiT -1 and -2; they transport the monovalent form of phosphorus

Question 11

what are the principal regulators of phosphorus reabsorption? (3)

Answer 11

PTH, phosphorus intake, FGF-23

Question 12

how does phosphorus intake affect phosphorus absorption? both short and long term effects?

Answer 12

the three C-terminal proteins on type IIa (TRL) bind to five proteins; (Shank2e, NHERF 1 & 2, PDZK 1 & 2); this is a microtubule dependent re-uptake phenomenon; there is a long-term mRNA expression change

Question 13

how does PTH regulated phosphorus uptake? what two things does this depend on?

Answer 13

internalization of NaPi-IIa/c channels via a clathrin coated pit mechanism - note: this process is one-way (the channels cannot make it back to the surface once they are endocytosed); KR residue dependent (no effect on NaPi-IIb); microtrubule dependent

Question 14

in what type of disease is FGF-23 overexpressed?

Answer 14

OHO - oncogenic hypophosphatemic osteomalacia

Question 15

what is the presentation of OHO?

Answer 15

hypophosphatemia
osteomalacia
renal phosphate wasting
low 1,25 dihydroxy Vit. D3 levels (supp. of 1-alpha hydroxylase)

Question 16

how can OHO be visualized?

Answer 16

an IGF-1 receptor PET scan using G-DOT visualizer

Question 17

is there FGF-23 in healthy people?

Answer 17

yes - it probably plays a role in Vitamin D regulation/phosphate homeostasis

Question 18

of the two main effects of FGF-23 (impact on NaPiII-a and Vit D block via 1-alpha hydroxylase) which happens first?

Answer 18

the block on 1-alpha hydroxylase takes place in 3 hours, the block on NaPiIIa happens in about 6

Question 19

is a cleaved form of FGF-23 effective? what can aid in the cleavage of FGF-23?

Answer 19

no; glycosylation brought on by a mutation in GALNT-3

Question 20

what role does Klotho play in FGF-23 binding?

Answer 20

it is a cofactor required for FGF-23 binding

Question 21

what does Klotho do besides FGF-23 cofactor?

Answer 21

removal of NaPi from membrane and TRPV5 is kept in the membrane