Role of Vitamin D on the Immune System in

Chronic Kidney Disease (CKD)

By: Margie Siegel

Outline

• Overview of Chronic Kidney Disease/Vitamin D

Synthesis
• Purpose of my review
• How vitamin D relates to the immune system in CKD
• FGF-23/Parathyroid Hormone
• Importance of Vitamin D in CKD patients
• Major Discoveries
• Take Home Message
Overview of
CKD8
Major Important Nutrients with CKD8
• Low protein (high biological value sources- eggs)
• Fluid restriction (replace output +500-1000 mL)
• Potassium
• Phosphorus (phosphate binders)
• Sodium
• Calcium
• Vitamin D

• Stages 1-4 have more strict requirements

• Stage 5 diet is slightly liberalized due to dialysis
Major Lab Values Measured with CKD8

• Glomerular Filtration Rate (GFR)

• BUN
• Creatinine
• Hemoglobin/Hematocrit (anemia is common)
• Glucose/HbA1c (diabetes is a common risk factor)
• Sodium
• Potassium
• Phosphorus
• Calcium
Overview of CKD8
Risk factors
• Age, gender race and ethnicity, family
history, drug use, smoking,
underlying diseases (hypertension
and diabetes)
• Symptoms
• Itching, muscle cramps, nausea,
vomiting, shortness of breath,
trouble sleeping
• Treatment
• Control your underlying disease (ex:
control blood sugar if diabetic)
• Internship experience: C-U Dialysis/DMH
Figure taken from
Krause’s Food & the
Nutrition Care Process
14th ed8
Vitamin D
Synthesis3
Purpose of Review

To show how supplementing Chronic Kidney Disease

(CKD) patients with Vitamin D can improve outcomes.
 Fibroblast Growth Factor (FGF-23)
• A hormone that is synthesized in the bones by osteoblasts and osteocytes.
• FGF-23 downregulates CYP27B1 in the kidneys which decreases the amount of 1,
25(OH)2D3 being produced.
• Immune relation:
• Decreased 1, 25(OH)2D3 causes high levels of FGF-23 which leads to impaired immune

How does function

• High levels of FGF-23 upregulate M1 macrophage and PMN recruitment but blocks M1

Vitamin D
macrophage from becoming M2 macrophage which causes only type 1 cytokines to be
expressed.
• Increased IL-6, TNFα, CRP, and fibrinogen exacerbate disease severity which inhibits

relate to the improved outcomes.

Immune
System in
CKD?5
Parathyroid Hormone (PTH)1

• PTH upregulates CYP27B1 and is released when calcium levels are low
• Serum 25(OH)D levels are low in CKD patients so 1,25(OH)2D cannot be made and PTH
levels increase
• High levels of PTH cause secondary hyperparathyroidism and hypercalcemia.
PTH study: Alvarez JA, Law J, Coakley KE, et al. 2012
• Objective: To determine whether high-dose cholecalciferol supplementation for 1 y in early
CKD is sufficient to maintain optimal vitamin D status (serum 25-hydroxyvitamin D
[25(OH)D] concentration ≥30 ng/mL) and decrease serum parathyroid hormone (PTH)
• Methods: vitamin D group was given 50,000 IU/wk for 12 wk followed by 50,000 IU every
other week for 40 wk
 Found that PTH levels decreased in the Vitamin
Found that Vitamin D insufficiency D group more than the placebo group
decreased as Vitamin D was
supplemented vs the placebo group
Importance of Vitamin D in CKD patients7,4
• Decreased levels in CKD are common due to Vitamin D deficiency causes
anorexia or inadequate diet

• If CDK patients 25(OH)D levels were tested more

often and supplementing earlier starting at Stage 3
CKD. This would cause patients to have better
control over PTH, calcium, and phosphorus levels.
Then the disease would not progress as rapidly
leading to improved quality of life and people able
being to live longer with CKD
Major Discoveries/Outcomes7,2
• When to test
• Kidney Disease Improving Global Outcomes
(KDIGO), suggests testing 25(OH)D levels starting
at stage 3 but no guidelines for how often.
Results of Supplementation
• Kidney Disease Outcomes Quality Initiative (K-
DOQI), suggests testing at stage 3 and up.

• How much to give and follow up time

• K-DOQI suggests 100,000 IU of cholecalciferol
should be given every 3-4 months and serum
25(OH)D levels should be monitored twice a year.
• Hemodialysis and Peritoneal patients should be
given 100,000 IU every 1-2 months. Treatment
should be stopped with calcium is above
10.5mg/dL.
• Vitamin D antagonists can be used to lower PTH.
With these, calcium and phosphorus need to be
monitored
Take Home Message

Vitamin D Supplementation in CKD patients is

essential to decrease FGF-23 and PTH levels to
decrease the risk for secondary
hyperparathyroidism and impaired innate
immune responses.
Sources

1. Alvarez JA, Law J, Coakley KE, et al. High-dose cholecalciferol reduces parathyroid hormone in patients with early chronic kidney disease: a pilot,
randomized, double-blind, placebo-controlled trial. Am J Clin Nutr. 2012;96(3):672-679. doi:10.3945/ajcn.112.040642
 
2. Bacchetta J, Pelletier S, Jean G, Fouque D. Immune, metabolic and epidemiological aspects of vitamin D in chronic kidney disease and transplant
patients. Clin Biochem. 2014;47(7-8):509-515. doi:10.1016/j.clinbiochem.2013.12.026
 
3. Bosworth C, de Boer IH. Impaired vitamin D metabolism in CKD. Semin Nephrol. 2013;33(2):158-168. doi:10.1016/j.semnephrol.2012.12.016
 
4. Cheng Z, Lin J, Qian Q. Role of Vitamin D in Cognitive Function in Chronic Kidney Disease. Nutrients. 2016;8(5):291. Published 2016 May 13.
doi:10.3390/nu8050291
 
5. Fitzpatrick EA, Han X, Xiao Z, Quarles LD. Role of Fibroblast Growth Factor-23 in Innate Immune Responses. Front Endocrinol (Lausanne). 2018;9:320.
Published 2018 Jun 12. doi:10.3389/fendo.2018.00320
 
7. Jean G, Souberbielle JC, Chazot C. Vitamin D in Chronic Kidney Disease and Dialysis Patients. Nutrients. 2017;9(4):328. Published 2017 Mar 25.
doi:10.3390/nu9040328
 
8. Mahan, L. K., & Raymond, J. L. (2017). Krause’s Food & the Nutrition Care Process (14th ed., pp. 711-723). St. Louis, MO: Elsevier.