1. Deprescribing Calcium-Based Phosphorus Binders in Dialysis Patients
Presented by Aaron Schmitz, Michael Russell, Kelsey Coffman
Project Advisor: Michelle Fravel

2. Outline Background Objectives Methods Results Conclusion
Future Directions

3. Background Chronic kidney disease complications
Bone and mineral disorder- Imbalance between phosphorus, calcium, parathyroid, and vitamin D
Hyperphosphatemia has been linked to
A reduction in alpha-1-hydroxylase activity causing decreased active vitamin D levels
An increase in parathyroid hormone
These effects cause increased CV mortality, morbidity, and all cause mortality
Hyperphosphatemia occurs in CKD because the kidneys are not able to excrete phosphorus efficiently leading to elevated serum levels of phosphorus
Vitamin D is activated in the kidneys by alpha-1-hydroxase and this function is impaired in CKD.
When phosphorus goes up and vitamin D goes down, the body makes PTH and this causes calcium to move from your bones into the blood. This leads to weakened bones and can lead to worsened cardiovascular outcomes

4. Background Maintaining phosphorus levels is a priority
Current treatments are dietary restriction, dialysis, and medication therapy
Medication therapy options
Calcium carbonate and Calcium acetate
Sevelamer HCl (Renagel) and Sevelamer carbonate (Renvela)
Lanthanum (Fosrenol)
2 new iron-based: Auryxia and Velphoro
Calcium-based binders are more common due to affordability, ease of use, and good patient tolerability
Serious adverse events with calcium-based binders
Large doses of all of these agents have to be taken with meals (2-3 large tablets with meals). Main side effects are GI disturbances
Sevelamer and Lanthanum became generic October 2017
Serious adverse events such as calcifications of arteries, cardiovascular arrhythmias, and increased risk of cardiovascular-related mortality have been associated with administration of high doses of calcium in patients with chronic kidney disease

5. Background
Kidney Disease: Improving Global Outcomes (KDIGO Guidelines) were updated in 2017 for bone and mineral disorders
Current Recommendation (2017): Restricting the dose of calcium-based phosphorus binders in all adult patients with CKD G3a-G5D (2B)
Driven by 3 RCT (Block 2012, Di Lorio 2012, Di Lorio 2013)
Previous Recommendation (2009): Restrict only in adults with hypercalcemia with CKD G3a-G5D (1B)
Data from RCT: Suggested increased harm with calcium-based phosphate binder utilization
G3a is Crcl 45-59
CKD-Mineral and Bone Disorder (CKD-MBD).” KDIGO, 21 June 2017

6. Di Lorio 2013
466 dialysis patients randomly assigned to sevelamer or calcium carbonate for 24 months, follow up until 36 months
Sevelamer arm resulted in lower phosphorus levels
Sevelamer treated patients experienced lower CV mortality due
Cardiac arrhythmias (HR 0.06; 95% CI , P < 0.001)
All cause CV death (HR 0.09; 95% CI ; P < 0.001)
Limitations: Open-label, higher baseline coronary artery calcification scores in calcium carbonate group
Trial with the largest effect was the dialysis population patients were either treated with a non-calcium-containing phosphate binder (sevelamer) or a calcium-based phosphate binder. The results of the trial showed that patients on non-calcium-containing therapy had a greater than 10-fold risk reduction (hazard ratios of 0.06 and 0.09, respectively)
Di Lorio, Biagio. Sevelamer Versus Calcium Carbonate in Incident Hemodialysis Patients: Results of an Open-Label 24-month Randomized Clinical Trial Pubmed, AJKD, 20 May 2013

7. Objectives
Describe the current prescribing patterns of calcium-based phosphate binders in patients receiving dialysis at the UIHC Center Dialysis Unit
Explore the opportunity to minimize the exposure to calcium-based phosphorus binders
Work with physicians to deprescribe calcium-based phosphorus binders
The University of Iowa Hospitals and Clinics has no standardized protocol for managing hyperphosphatemia

8. Methods
Chart Review
We reviewed the charts of 46 patients receiving dialysis at University of Iowa Hospitals and Clinics who were currently taking a phosphate binder.
Patient demographics, phosphate binding therapy, and lab values were collected.
Targeted one dialysis site at UIHC and patients that were taking phosphate binder

9. Methods
Patients were categorized based on their phosphate binding therapy into one of three treatment categories:
Calcium-based binding therapy
Sevelamer binding therapy
Sevelamer + Calcium-based binding therapy (dual therapy)
Add slide after this that includes: demographics and reasons for switching

10. Methods
We analyzed each phosphate binder therapy category for patterns related the patient demographics including age and gender.
If patients had been on alternative phosphate binder therapy previously we examined factors related to the switch including:
What the reason for the switch was (adverse events, changes in lab values, etc.)
If the switch occurred before or after the KDIGO guideline update

11. Methods
Lab values related to phosphate binder therapy were then examined for each treatment category. We used the average of their three most recent results to categorize their levels as: low, normal, high and fluctuating.
Calcium Phosphate
Low
< 8.5 mg/dl
Medium
mg/dl
High
> 10.5 mg/dl
Fluctuating
Variable
Low
< 2.5 mg/dl
Medium
mg/dl
High
> 4.5 mg/dl
Fluctuating
Variable

12. Results Total patients = 46 Calcium - 22/46 Sevelamer - 19/46
Combo - 5/46
If we have X number of patients at UIHC, this many people would be on calcium, sevelamer, etc.

13. Results
If we got rid of all the low levels, how many patients could benefit from intervention? Add another graph

14. Results
If we got rid of all the low levels, how many patients could benefit from intervention? Add another graph
Green box = possible intervention group; 14 patients

15. Results
14 / 46 overall patients

16. Results
Star = intervention group

17. Results
Fluctuator = had low, medium, and high levels for past 3 readings
Another potential intervention = low phosphorus on calcium based binder; should back off; percent of patients

18. Results
Fluctuator = had low, medium, and high levels for past 3 readings
Another potential intervention = low phosphorus on calcium based binder; should back off; percent of patients
Potential intervention on an additional 3 patients

19. Conclusion
Non-calcium-based phosphorus binders are preferred in chronic kidney disease
Possible intervention groups for patients currently on calcium-based binders include patients with
Normal or high calcium levels
Low phosphorus levels
Of the 46, how many could we make a recommendation on based on calcium/phosphorus levels?
17 / 46 total
17 / 22 on calcium therapies

20. Future Direction
Work with physicians to deprescribe calcium-based phosphorus binders where appropriate
Evaluate the effect of deprescribing efforts on
Maintenance of calcium-based binder dose de-escalation/discontinuation
On clinical endpoints

21. Questions?
Deprescribing Calcium-Based Phosphorus Binders in Dialysis Patients at UIHC
Aaron Schmitz, Kelsey Coffman, Michael Russell
Project Advisor: Michelle Fravel, PharmD, BCPS