Block 4: CKD Complications Flashcards
What are the symptoms of CKD-MBD?
- Bone pain
- Skeletal fracture
- Vasculature calcification
What are the symptoms of anemia?
- Fatigue
- SOB
- Cold tolerance
- Tingling in extremities
What is CKD-MBD?
Systemic disorder of mineral and bone metabolism from CKD
What are the manifestations of CKD?
- Abnormal phosphorus, calcium, PTH, FGF23, or vitamin D
- Abnormal bone turnover
- Vascular or soft tissue calcifications
What are the clinical manifestations of CKD?
symptomatic = irreversible damage
Prevention is key
How should we monitor the stages of CKD?
What are the goals of CKD monitoring?
- Avoid hypercalcemia
- Maintain Phos towards normal range
- Avoid PTH elevations (2-9 x ULN in ESRD)
What are the normal lab values for CKD?
- Corrected Calcium 8.4 -10.2 mg/dL
- PTH (normal 10-65 pg/mL):
Stage 3 CKD: 35-70 pg/mL
Stage 4: 70-110 pg/mL
Stage 5: 200-300 pg/mL (2-5 x ULN)
HD: 2-9 x ULN - Phosphorous 3-4.5 mg/dL
- 25(OH)D >30 ng/mL
How should you first manage elevated PTH?
Evaluate phosphorus, calcium, vitamin D, PTH
What do you do if phosphorus is the cause of CKD?
- Reduce dietary phosphorus (reduction of protein sources)
- Phosphate binders
What is the first line phosphate binder?
Calcium-based binders:
Carbonate and acetate
What are the resin binders? When do you use it?
Sevelamer HCl and carbonate
If patient has normo or high calcium
What are iron-based binders?
- Ferric citrate: anemia, iron overload
- Sucroferric oxyhydroxide
What are the ADRs of phosphate binders?
- Constipation
- NVD
- Abdominal pain
- Hypercalcemia with calcium binders
- Iron overload with ferric citrate
What are the counseling points of phosphate binders?
- Take with food → binds to food in intestine
- Space out with iron, zinc, quinolone ABX (1-2 hr before or 3 hr after binder)
- Have blood work done regularly to check phosphate levels
What are KDIGO rec for phosphate binders?
- Calcium based binders max 1500 mg elemental calcium (can add non-calcium binders if max dose is reached)
- Consider non-calcium based binder in HD patients with calcifications
What is the treatment if vitamin d def is a cause of the CKD?
- Nutritional
- Calcitriol
- Vitamin D analogs
What are the nutritional vit d?
- Ergocalciferol (D2)
- Cholecalciferol (D3)
- Calcifedial (prohormone): already activated
What are the vitamin d analogs?
- Paracalcitol
- Dovercalciferol
What is the difference between D2 and D3?
D3: animal
D2: plant
Activated by the liver then kidney
What are the dosing of D2 and D3?
D<30: 50,000 IU PO QM x 6 months
D<5: 50,000 IU PO QW x 12 weeks then monthly x 6 months
How does calcifediol differ from D2 and D3? Dosing?
No need liver activation but kidney activation
Dose: 30 mcg PO QD
Increase the level more rapidly
What is calcitriol? ADRs?
Activated form increases 25 OHD quicker than the other
Risk of hypercalcemia and phospatemia
Extensive PPB
How is calcitriol dosed?
0.25 mcg po daily or 1-2 mcg IV TIW
in what instance would you not use calcitriol?
Cautioned for CKD 5 cause it is non-dialyzable
What is the MOA of vitamin D2 analogs?
Mimic Vitamin D without increasing Ca/P due to its direct action on the PT gland
What is the dosing for paracalcitol? Metabolism?
ND: PTH </=500: 1 mcg po daily or 2 mcg po TIW
PTH >500: 2 mcg po daily or 4 mcg po TIW
ESRD: 0.04-1 mcg/kg IV TIW
Active as given and undergoes CYP3A4 metabolism
What is the dosing of doxercalciferol? Metabolism?
ND: 1 mcg po daily
ESRD: 10 mcg po TIW
Requires conversion by liver to active form
What is first line vitamin D for CKD-ND?
1st: Nutritional vitamin D
Calcitriol and vitamin D analogs for G4-5 with severe and progressive hyperPT
What vitamin D recommended for HD?
Calcitriol, vit d analog and/or calcimimetics
What are the ADRs of vitamin D?
- Hypercalcemia
- Hyperphosphatemia
What are examples of calcimimetics?
- Cinacalcet
- Etelcalcetide
How do you dose cinacalcet? Counseling point? Metabolism?
30 mg PO QD
CYP metabolism and high PPB
Take with food
How do you dose etelcalcetide? Metabolism?
5 mg IV TIW
Renal cleared
What is the MOA of calcimimetics? Warning?
↑ sensitivity of Ca-sensing receptor on PTH gland
Only approved for ESRD
Don’t start if corrected Ca below normal
What is the ADR of calcimimetics?
Hypocalcemia, N/V
What is the primary cause of anemia?
↓ EPO production and ↓ RBC production
What is the secondary cause of anemia?
↑ hepcidin → ↓ GI iron absorption
What are the symptoms of anemia?
- Fatigue
- SOB
- Cold intolerance
- Tachycardia
- Tingling in extremities
- HA
- Malaise
How do you diagnose anemia?
- Symptoms
- Hgb <13 in males; ,12 in females
- Iron saturation: normal range 20 -50 % , if < 30 %
- Ferritin normal range 15-200 ng/Ml, higher in CKD. If < 500 ng/dL
How often do you monitor Hgb?
CKD 3: yearly
CKD 4-5: Bianually
CKD 5D: Q3M
What are the treatment options for anemia?
- PO and Injectable iron
- Injectable ESA
What are the types of PO iron?
- Ferrous (sulfate, fumarate, gluconate)
- Ferric maltol
- Polysaccharide iron complex
- Carbonyl iron
How do you dose PO iron?
200 mg elemental iron/day
How much elemental iron is in oral preparations?
Ferrous sulfate 20%: 325mg
Fumarate 33%: 325 mg
Gluconate 12%: 324 mg
Iron polysaccharide 100%
Carbonyl iron 100%
Ferric maltol 100%
What are the IV iron preps?
Iron dextran (1st gen)
Iron sucrose
Sodum ferric gluconate (2nd gen) → HD
Ferric carboxymaltose (3rd gen) → anemia
Ferumoxytol (3rd) → anemia
What IV iron preps can cause anaphylaxis?
Ferumoxytol
Iron dextran
What are the ADRs of PO iron?
- GI: constipation, nausea, cramping
- Take w/ food to reduce but will reduce absorption
- DI with calcium products, antacids, tetracyclines
What are the ADRs of IV iron?
- Allergic reaction, hypotension, DZ, dysnpea, HA → reduce dose
- Anaphylaxis for dextran and ferumoxytol
- Avoid in active infections
What is the KDIGO rec for iron therapy?
PO: 1st line in non-HD patients (1-3 month trial before initiating IV)
IV: 1st line for HD/PD patients (2nd line for non-HD patients)
When should you give iron for anemia?
Hgb <13 in males; <12 in female
+
TSAT <30 % and Ferritin < 500 ng/mL
When do you give ESA?
Hgb <10 without iron deficiency
Do not target Hgb >11.5
What are the ESA products?
What are the ADRs of ESA therapy?
- HTN
- Thrombosis
- Anitbody-mediated PRCA (pure red cell aplasia)
ESA >8 weeks with sudden Hgb drop (0.5-1 per week or 2 transfusion/week) with ARC (reticulocyte count) <10 with normal platelet and WBC
DC ESA
What is the recommendation of ESA for Non-HD?
Darbepoetin and methoxy PEG-epoetin preferred due to longer half-lives
Consider costs of each agent
SQ preferred for patients w/o IV access
How do you monitor ESA?
Initiated when Hgb <10
Weekly Hgb levels after initiation
Monthly Hgb levels once stable
Do not INCREASE the dose more frequently than monthly
Reduce or DC if Hgb approaches 11 in HD patients or 10 in non-HD patients
How do you monitor ESA weekly based on Hgb levels?
DECREASE dose by 25% if Hgb rises >1 g/dL in 2 weeks
Increase dose by 25% if Hgb hasn’t increased by 1 g/dL in 4 weeks
How do you monitor ESA monthly based on Hgb levels?
Acceptable Hgb increase is 1-2 g/dL per month
What is ESA hyporesponsiveness?
- No increase from baseline after 1 month
- Do not escalate beyond double the initial dose
- If inadequate response after 12 weeks of dosing escalations, patients will likely not respond
What is the MOA of antibody-mediated PRCA?
Antibodies that inhibit erythopoiesis
When do you use antibody-mediated PRCA?
Patients on >8 weeks of ESA who’s:
1. Hgb decreases 0.5-1 g/dL per week OR
2. Require 1-2 transfusions per week, with Normal platelets and WBCs, AND
Abs reticulocyte count <10,000
How do you manage antibody-mediated PRCA?
- DC ESA
- Give peginesatide 0.04 mg/kg SQ/IV QM
