CKD complications 2

Question 1

CKD - Mineral Bone Disorder

defined by 1 or more of:

Answer 1

○ Abnormalities of calcium, phosphorous, parathyroid hormone or vitamin D metabolism
○ Abnormalities of bone turnover, mineralization volume, linear growth or strength (increased risk of fracture)
○ Vascular or other soft-tissue calcification
● Renal osteodystrophy (renal bone disease)
○ Skeletal component of CKD-MBD quantifiable by bone biopsy
● More prevalence at CKD stage 4 and stage 5

Question 2

Vitamin D

Answer 2

● Ergocalciferol (Vitamin D2
) - ingested in food and supplements
○ No role in our CKD discussion
● Cholecalciferol (Vitamin D3
) - ingested in food or produced by the effect of UV
light on the skin
● Both are “inactive” forms of Vitamin D
● To become active cholecalciferol must first be hydroxylated by the liver, then
by the kidneys to become 1, 25 dihydroxyvitamin D3
, or calcitrio

Question 3

Parathyroid Hormone

roles

Answer 3

promotes the following:
● Decreased phosphate reabsorption within the kidney
● Increased calcium reabsorption by the kidney
● Increased calcium mobilization from the bone
● Stimulates production of active vitamin D (calcitriol) within the kidney

● Calcitriol promotes increased intestinal absorption of calcium (and phosphate)
which suppresses production of PTH
● Low calcium levels stimulate the production of PTH
● High calcium levels suppress production of PTH
● Hyperphosphatemia promotes an increase in FGF-23, which reduces
phosphate by decreasing renal tubular absorption and decreasing calcitriol
production

Question 4

Pathophysiology

Answer 4

1. Decreased kidney function leads to reduces phosphate excretion and
   increased serum phosphate
2. Elevated phosphate directly suppresses calcitriol production
3. Elevated phosphate leads to increased FGF-23, leading to decreased
   calcitriol
4. Reduced kidney mass leads to decreased calcitriol production
5. Decreased calcitriol with reduced calcium absorption from the GI tract leads
   to hypocalcemia
6. Steps 1-5 lead to increased production of PTH and proliferation of parathyroid
   cells

Question 5

Secondary Hyperparathyroidism

Answer 5

Bone disease is due to secondary hyperparathyroidism which is related to
abnormal mineral metabolism
● High bone turnover disease
○ Phosphate retention
○ Decreased free calcium concentrations
○ Decreased calcitriol
○ Reduced expression of vitamin D3 receptors and calcium sensing cells
○ FGF-23 elevates which contributes to decreased calcitriol synthesis.

Question 6

Adynamic or Low-bone turnover disease

Answer 6

● Results from calcium and vitamin D3 supplementation an dover suppression
of PTH
● Can result from aluminum deposition
● Results in marked low bone turnover but normal mineralization
● Treatment: Stop vitamin D3 (calcitriol) supplementation (and sometimes
calcium) and any aluminum containing phosphate binders

Question 7

KDIGO 2017:

treatment targets

Answer 7

KDIGO 2017:
•Stage 3-5 CKD*
○ Non-dialysis (ND) - maintain phosphate in the normal range.
○ Dialysis – lower to the normal range
•Calcium – maintain in the normal range
•PTH – optimal target is unknown in ND patients. Dialysis : 2-9 x ULN
*Canadian Society of Nephrology recommends no routine
monitoring of calcium, phosphate and PTH prior to stage 4

Question 8

Non-pharmacological management: Dietary phosphate

restriction

Answer 8

High phosphate foods
● Cheese, chocolate, cola, beans, legumes,
nuts, fish, peanut butter, egg yolk,
processed meats/foods, bran
Low phosphate foods
● Jell-O, rice milk, unsalted popcorn,
pretzels, green beans, egg white, clear
sodas, jam/jelly, honey, beef, turkey,
chicken, 

Dialysis tends to remove some
phosphate, so there are more dietary
restrictions pre-dialysis

Question 9

PHOSPHATE BINDERS

3 tyoes

Answer 9

Calcium –based binders
metal-based
non-calc, non-metal binders

Question 10

Calcium –based binders

Answer 10

Calcium carbonate :
Tums
Caltrate
Os-cal

Calcium acetate: PhosLo

Question 11

Metal-based binders

Answer 11

Magnesium hydroxide Various brands

Aluminum hydroxide: Amphojel, Basaljel

Question 12

Non-calcium, non-metal binders

Answer 12

Sevelamer hydrochloride: Renagel

Sevelamer carbonate: Renvela

Question 13

Phosphate Binders

● All phosphate binders are effective
● There is not enough evidence that any of the binders significantly impact
patient outcomes
● Choice of binder will depend on other factors such as CKD stage, side effects,
laboratory parameters.

Answer 13

● All phosphate binders are effective
● There is not enough evidence that any of the binders significantly impact
patient outcomes
● Choice of binder will depend on other factors such as CKD stage, side effects,
laboratory parameters.

Question 14

Calcium Salts

Answer 14

● Raises calcium levels
● Must be given with meals to be effective as a phosphate binder
● Usual dose is 0.6-4.5g of elemental calcium per day
○ Calcium carbonate (TUMS regular, 200mg elemental calcium) three times a day with meals
○ Titrate on basis of calcium and phosphate levels
○ Give higher doses with bigger meals
● Carbonate salt (highest % elemental calcium) - 40%
● Acetate - 25%
● Citrate - 21%

Question 15

Calcium Salts

side fx

Answer 15

● Caution: potential for interactions with respect to administration times (iron,
fluoroquinolone antibiotics)
● Side effects:
○ Hypercalcemia - if calcium > 2.54, reduce dose or switch to non-calcium binder
○ Nausea
○ Constipation

Question 16

Aluminum Salts

Answer 16

● High phosphate binding potency (most potent)
● Reserved for acute treatment of severe hyperphosphatemia
● Risk of aluminum toxicity (CNS toxicity, worsening of anemia)
● Short term therapy limited to maximum of 4 weeks
● No longer recommended as first line therapy
● Dosage 300-600mg three times daily with meals.

Question 17

Magnesium Salts

Answer 17

● Magnesium hydroxide, Magnesium carbonate
● Adverse effects:
○ Diarrhea
○ Hypermagnesemia
● For short term or adjuvant use after other agents fail
● Less effective than calcium salts

Question 18

Sevelamer (Renagel® HCl, Renvela® carbonate)

Answer 18

● Non-absorbable hydrogel
● Least potent phosphate binder
● Does not contain calcium, aluminum or magnesium
● 800-2400 mg three times daily with meals (swallowed whole)
● Second line agent due to cost (not covered)
● May also decrease LDL cholesterol
● Less effective if phosphate > 2mmol/L
● Side effects: mainly GI - constipation, diarrhea, nausea, vomiting, abdominal
pain, metabolic acidos

Question 19

Agents to treat hyperparathyroidism

Active Vitamin D3

Answer 19

Active Vitamin D3
● Stimulate absorption of serum calcium (and phosphate) by intestinal cells and
through direct activity on the parathyroid gland to decrease PTH synthesis
● Use in patients with elevated PTH despite use of calcium containing products
● Ideal to have phosphate controlled prior to initiation
○ Increases GI phosphate absorption
○ Not initiated if phosphate > 2 mmol/L or Calcium > 2.7 mmol/L

Question 20

Calcitriol (Rocaltrol®)

Answer 20

● Active form of vitamin D3
● Oral: 0.25mcg/day or every other day (up to 0.5-1mcg /day)
○ Increases should be made at 4-8 week intervals
● IV: 0.5mcg/day 3x per week (up to 3mcg/day 3 x per week) if undergoing
hemodialysis
● Adverse effects: hypercalcemia (33%), headache, pruritus, hyperphosphatemia, hypermagnesemia, metallic taste, nausea, elevated liver
enzymes, bone pain, soft tissue calcification

Question 21

Synthetic Vitamin D3 Analogues

Answer 21

● More affinity for the kidney receptors may result in less GI absorption of
calcium and phosphate compared to calcitriol
● Typically reserved for patients on dialysis as the are given parenterally.
○ Alfacalcidol (available in Canada)
○ Paricalcitol (USA)
○ Doxercalciferol (USA

Question 22

Calcimimetics

Answer 22

○ Increase the sensitivity of the calcium-sensing receptors of the parathyroid gland
○ Cinacalcet (Sensipar®) - $$$$
■ 30 mg once daily orally, maximum 180 mg /day
■ A/E: GI upset, QT prolongation leading to arrhythmias

Question 23

● Parathyroidectomy

Answer 23

○ When medical therapy is unsuccessful

Question 24

Extraskeletal manifestations of CKD-MBD

Answer 24

● Soft tissue calcification
○ Blood vessels
○ Heart valves
○ Skin
● Calciphylaxis
○ 1-4% of dialysis patients
○ Extensive calcifications of skin, muscles, and subcutaneous tissues
○ Leads to non-healing ulcerations and gangrene

Question 25

Key Points - CKD-MBD

Answer 25

● Important to try and maintain calcium and phosphate homeostasis
● Monitor at CKD Stage 4 and 5
● Stepwise approach:
○ Phosphate binders (and dietary interventions) - calcium, non-calcium
○ Active Vitamin D3
○ Beware of over-suppressing PTH which can also lead to bone disease

Question 26

Electrolyte Disturbances

Answer 26

Sodium and water retention
● Hyperkalemia
● Hypermagnesemia
○ Decreased elimination of Mg by kidney
○ Avoid Mg containing antacids

Question 27

Metabolic acidosis

Answer 27

● Inability of kidney to produce sufficient bicarbonate
● Consider treatment with bicarbonate supplements when levels < 22mmol/L
● Chronic metabolic acidosis reduced the kidneys synthesis of active vitamin D
and may limit calcium absorption from the diet.

Question 28

Other complications

Answer 28

● Restless leg syndrome
● Leg cramps
● Other symptoms of uremia
○ Itching
○ Decreased appetite
○ nausea/vomiting