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1/ Rounding in our large HD unit past 3 wks & teaching @thehappykidneys @JCummingsMD about P @ sec hyperparathyroidism (secHPT), one of the frustrating topics in Neph. Little data but expert opinions have set goals for P and PTH that pts, MDs, dietitians try to achieve ...
2/ Pathophysiology of secHPT is complicated. Trade-off hypothesis was first proposed by Dr. Neil Bricker (first @WUNephrology chief) and Dr. Ed Slatopolsky in 1969 to explain development of secHPT. 
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/575565 https://www.nejm.org/doi/full/10.1056/NEJM197205182862009
https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/575565 https://www.nejm.org/doi/full/10.1056/NEJM197205182862009
3/I use a variation of this figure from the NEJM paper to discuss secHPT.
In early CKD, P & Ca remain in the normal range at expense of elevated PTH
Eventually GFR deteriorates to the point where compensation no longer occur
Check out the original figure from 1969 paper
In early CKD, P & Ca remain in the normal range at expense of elevated PTH Eventually GFR deteriorates to the point where compensation no longer occurCheck out the original figure from 1969 paper
4/ FGF-23 not known in 1970s.
This @CJASN review depicts the complicated, convoluted and intricate Ca – P – Vit D – FGF-23 - 1,25OHVitD – PTH interactions in normal individuals and those with CKD.
https://cjasn.asnjournals.org/content/6/4/913 .
Did I mention it is complicated????
This @CJASN review depicts the complicated, convoluted and intricate Ca – P – Vit D – FGF-23 - 1,25OHVitD – PTH interactions in normal individuals and those with CKD.
https://cjasn.asnjournals.org/content/6/4/913 .
Did I mention it is complicated????
5/
SecHPT assoc with: bone pain, fractures, vascular and valvular calcification, worsening anemia, dec response to ESA, calciphylaxis etc
Management:
Control of phos (diet/binders)
Active Vitamin D
Calcimimetics
PTX
SecHPT assoc with: bone pain, fractures, vascular and valvular calcification, worsening anemia, dec response to ESA, calciphylaxis etc Management:Control of phos (diet/binders)Active Vitamin DCalcimimeticsPTX
6/Low P Diet
Dietary P restriction about 1000 mg/day
Restricting P is hard, esp with need for adequate protein intake
Some high P foods
Dairy
Organ meats, sardines,
Processed foods
nuts,quinoa
Dark sodas
Cocoa/chocolate
Oatbran
for Aussie friends -Vegemite!
Dietary P restriction about 1000 mg/dayRestricting P is hard, esp with need for adequate protein intakeSome high P foods
DairyOrgan meats, sardines,Processed foodsnuts,quinoaDark sodas Cocoa/chocolateOatbran for Aussie friends -Vegemite!
7/ P binders (not all used now or approved)
Aluminum
Calcium
Magnesium
Sevelamer
Lanthanum
Iron
Niacin/nicotinamide
Chitosan chewing gum
For periodic table/chemistry geeks
I couldn't find the rationale as to why Al became the first one tried
Aluminum CalciumMagnesiumSevelamerLanthanumIronNiacin/nicotinamide Chitosan chewing gumFor periodic table/chemistry geeks
I couldn't find the rationale as to why Al became the first one tried
8/Aluminum
Excreted by the kidneys
Accumulation of Al led to osteomalacia/adynamic bone disease, encephalopathy, dementia
No longer used in US and other countries
In hindsight - probably not a good idea to use as a binder in pts without kidney function
Excreted by the kidneys Accumulation of Al led to osteomalacia/adynamic bone disease, encephalopathy, dementia No longer used in US and other countries In hindsight - probably not a good idea to use as a binder in pts without kidney function
9/ Calcium based binders
CaCO3
Work done by @WUNephrology led by Dr. Slatopolsky paved the way for use of CaCo3
https://www.nejm.org/doi/10.1056/NEJM198607173150304
Ca acetate came later. Assoc with less hypercalcemia vs CaCO3, but remains more expensive
Ca acetate now available as liquid
CaCO3Work done by @WUNephrology led by Dr. Slatopolsky paved the way for use of CaCo3 https://www.nejm.org/doi/10.1056/NEJM198607173150304Ca acetate came later. Assoc with less hypercalcemia vs CaCO3, but remains more expensiveCa acetate now available as liquid
10/Sevelamer
P lowering incidentally discovered while studied to 
chol
Sevelamer HCL (FDA app 2000). https://academic.oup.com/ndt/article/13/9/2303/1808023
Sevelamer HCL assoc with acidosis 
Sevelamer CO3 (Renvela) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781155/
Renvela FDA approved 2007 -available as pills and powder
P lowering incidentally discovered while studied to cholSevelamer HCL (FDA app 2000). https://academic.oup.com/ndt/article/13/9/2303/1808023Sevelamer HCL assoc with acidosis Sevelamer CO3 (Renvela) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2781155/ Renvela FDA approved 2007 -available as pills and powder
11/Lanthanum Carbonate (Fosrenol, FDA approved 2004)
Used to remove P from lakes/ponds! https://www.phoslock.eu/what-is-phoslock
Needless to say some hesitancy in using it early on
Advantage over Al -excreted through GItract
Available as chewable pill and powder https://www.sciencedirect.com/science/article/pii/S0272638603005547?via%3Dihub
Used to remove P from lakes/ponds! https://www.phoslock.eu/what-is-phoslock Needless to say some hesitancy in using it early onAdvantage over Al -excreted through GItractAvailable as chewable pill and powder https://www.sciencedirect.com/science/article/pii/S0272638603005547?via%3Dihub
12/Iron based binders
Sucroferric oxyhydroxide (Velphoro, FDA approved 2013)
Iron based chewable pill
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150998/
Ferric Citrate (Auryxia approved 2014
non-chewable pill
Only binder approved for rx of Fe def anemia
Great review: https://www.jrnjournal.org/article/S1051-2276(16)00010-8/pdf
Sucroferric oxyhydroxide (Velphoro, FDA approved 2013)Iron based chewable pill https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4150998/
Ferric Citrate (Auryxia approved 2014 non-chewable pill
Only binder approved for rx of Fe def anemiaGreat review: https://www.jrnjournal.org/article/S1051-2276(16)00010-8/pdf
13/How to use/choose binders
? (I have no COI)
One is not "better" than the other
If serum Ca is low or low-normal – start with ca binder
After that –trial and error, and COST!
What works for one pt doesn’t work for other
All have GI SE of varying degree/manifestations
? (I have no COI)One is not "better" than the otherIf serum Ca is low or low-normal – start with ca binderAfter that –trial and error, and COST!What works for one pt doesn’t work for otherAll have GI SE of varying degree/manifestations
14/Other caveats
CaxP is meaningless - number pulled out of thin air by KOL long time ago. Hhave discussed this with Dr.S :-)
serious GI SE can occur https://pubmed.ncbi.nlm.nih.gov/28852493/
Most binders contraindicated in those with high risk for SBO, or have other GI complications
CaxP is meaningless - number pulled out of thin air by KOL long time ago. Hhave discussed this with Dr.S :-) serious GI SE can occur https://pubmed.ncbi.nlm.nih.gov/28852493/ Most binders contraindicated in those with high risk for SBO, or have other GI complications
15/Waiting for 2 important RCTs to see if any of this leads to meaningful outcomes
Hi-Lo: https://www.ajkd.org/article/S0272-6386(20)31131-8/fulltext
PHOSPHATE trial: https://clinicaltrials.gov/ct2/show/NCT03573089
Shoutout to @WUNephrology stalwarts/mentors Drs. Slatopolsky,Delmez and others who did so much work in this area
Hi-Lo: https://www.ajkd.org/article/S0272-6386(20)31131-8/fulltext PHOSPHATE trial: https://clinicaltrials.gov/ct2/show/NCT03573089Shoutout to @WUNephrology stalwarts/mentors Drs. Slatopolsky,Delmez and others who did so much work in this area
