anemia Flashcards
how is anemia in CKD defined?
HGB < 13 g/dL for males
HGB < 12 g/dL for females
what are the goals of therapy for anemia of CKD?
- increase O2 carrying capacity
- improve QOL
- prevent/alleviate symptoms and complications of anemia
- decrease need for blood transfusions
when does anemia begin to develop?
as GFR declines < 45 ml/min/1.73m^2
what are some baseline labs to assess in anemia?
- HGB
- serum iron
- serum ferritin
- transferrin saturation (Tsat)
what is ferritin?
the storage form of iron
what is transferrin saturation?
reflects the functional iron available for immediate erythropoesis
hepcidin MOA
inhibits ferroportin channel that absorbs Fe to be used
do CKD patients have high or low hepcidin and what is the effect?
high hepcidin -> hepcidin is excreted by the kidneys so it accumulates in CKD patients
causes iron deficiency since ferroportin stops working due to lots of hepcidin
what is the most common cause of erythropoietin resistance?
iron deficiency
how often should the iron panel be monitored?
every 3 months in an ESRD patient and anyone receiving EPO for anemia
what is the therapeutic response to iron?
- increase in reticulocyte count within 7-14 days
- increase in HGB and HCT within 3-4 weeks
what must be done prior to initiating an ESA (EPO stimulating agent)?
must correct iron deficiency FIRST
what are the goals of therapy for anemia in CKD?
Tsat > 30%
Serum Ferritin > 500 ng/mL
when and why should IV iron be held?
Tsat > 50% or Ferritin > 1200 ng/mL
due to risk of iron overload
how often should HGB and HCT be checked once ESA therapy is initiated?
weekly during therapy
how often should Tsat and serum ferritin be checked?
every 3 months
what are some disadvantages of oral iron therapy?
- poor absorption
- GI complications: nausea, constipation
- poor adherence (<50%)
- slow replenishment of iron stores
what is an advantage to oral iron therapy?
inexpensive
what are some advantages of parenteral iron therapy?
- better absorption
- rapid replenishment of iron stores
what are some advantages of parenteral iron therapy?
- better absorption
- rapid replenishment of iron stores
what are some adverse effects of oral iron therapy?
- GI: nausea, cramping, constipation
- dark stool
- MANY DDIs (e.g. calcium carbonate, antacids)
what are some adverse effects of IV iron therapy?
- dyspnea/wheezing, itching, myalgias
- hypotension, flushing, edema
- chest pain, cardiac arrest
- injection site reaction, anaphylactoid and anaphylactic reactions
- INFECTION!!
when should we AVOID giving IV iron?
in patients with active systemic infection
traditional target oral iron dosing
target 200 mg of elemental iron/ day in divided doses
ex: ferrous sulfate 325 mg PO TID
ferrous sulfate
tablet: 325 mg (65) or 195 mg (39) 20% elemental iron
ferric citrate
tablet: 210 mg (210) 100% elemental iron!
oral iron DDIs
drugs that decrease iron absorption:
- Al, Mg, and Ca containing antacids
- tetracyclines
- H2 antagonists
- PPIs
- cholestyramine
oral iron NEEDS gastric acid to be absorbed!
object drugs affected by iron
- fluoroquinolones
- levothyroxine
- tetracyclines
- mycophenolate
- methyldopa
- levodopa
separate administration by ~ 2 hrs!
IV iron formulations
ferric gluconate
iron sucrose
IV therapy clinical pearls
- IV iron is the preferred therapy in dialysis patients
- in NON-dialysis patients: a 1-3 month trial of oral iron can be used
-> can convert to IV if no response > 3 months
what are the goals of iron therapy in CKD?
Tsat ≥ 30% (limit of 50%)
Serum ferritin ≥ 500 ng/mL (limit of 1200 ng/mL)
how often should routine monitoring of Tsat and serum ferritin be done?
at least every 3 months
epoetin alfa brand name
Epogen
dosing of epoetin alfa
either 3 times a week IV OR once weekly SubQ (preferable due to cost saving)
darbepoetin alfa brand name
Aranesp
dosing of darbepoetin alfa
once a week or every 2 weeks (IV or SubQ)
methoxy polyethylene glycol epoetin beta brand name
Mircera
dosing of methoxy polyethylene glycol epoetin beta
every 2-4 weeks
which is the longest acting ESA?
methoxy polyethylene glycol epoetin beta
- can be given up to once a month!
MOA of methoxy polyethylene glycol epoetin beta
continuous erythropoietin receptor agonist
epoetin alfa epbx brand name
Retacrit
dosing of epoetin alfa epbx
3 times a week IV OR once weekly SubQ
which ESA is the cheapest?
epoetin alfa epbx
-> is a biosimilar of epoetin alfa
FDA initiation guideline for ESAs and Hemoglobin targets
initiation of ESA: if < 10 g/dL (ESRD)
target HGB: 10-11 avoid transfusions
is it normal to give ESA and NOT see any changes in HGB and HCT?
YES -> wait and watch, don’t do anything
what is the goal change in HGB when starting ESAs?
1-2 g/dL/month
when should we dose adjust ESAs after initiation?
4 weeks (steady state)
when should we reduce the ESA dose by ≥ 25%?
if patient’s HGB approaches 11 g/dL or if HGB increases > 1g/dL in 2 weeks or less!
when should we increase the ESA dose by 25%?
if patient’s HGB is below target after 4 weeks of treatment
when to hold ESA dose in ND-CKD patients?
when HGB > 10
when to hold ESA dose in D-CKD patients?
when HGB > 11 (11-12; APPROACHING 12 is when you want to hold)
ESA hyporesponsiveness
- no increase in HGB after first month of appropriately dosed ESA
- Two ESA dose increases after stable period to maintain HGB
ESA resistance
failure to achieve a target HGB at a dose of > 500 units/kg/week (5x starting dose)
Causes of ESA Resistance
- IRON DEFICIENCY!!
- ACEIs
- Hyperparathyroidism
- Aluminum toxicity
- Folate and/or Vitamin B12 deficiency
- Infection*
- Malignancy*
- Trauma*
- Inflammation*
*decrease bone marrow responsiveness to EPO
ESA Adverse Effects
HTN (dose-dependent)
Hypercoagulability -> increased risk of thrombosis (DVT, PE, MI, CVA, etc.)
Hypersensitivity rxns
PRBCA: Pure Red Blood Cell Aplasia
Headache, fatigue, edema
Progression of malignancy
BBW for ESAs in CKD
greater risk of death, serious adverse cardiovascular reactions, and stroke when administered ESAs to target a HGB level > 11 g/dL
ESA Monitoring Parameters (initial phase -> maintenance phase)
HCT/HGB: 2x a week -> 1-2x a month
BP: 3x a week -> 3x a week
Ferritin: monthly -> quarterly
TSat: monthly -> quarterly
CBC, BUN/Cr, K, Phos: 2x a month -> 1x a month
Reticulocytes: 1x a week -> quarterly
ESA Clinical Pearls
- these agents do NOT decrease mortality
- can be administered IV or SubQ (IV preferred in dialysis and SubQhas longer duration of effect and saves costs)
- DO NOT USE IF: active malignancy, high risk of CVA, and HGB > 11 g/dL
when are PRBCs given?
packed red blood cells are given when severe anemia occurs (HGB < 7 g/dL)
-> rapid correction of O2 carrying capacity
every 1 unit of PRBC causes what effect on HGB?
a 1 g/dL increase in HGB
1 unit of PRBC contains how much elemental iron?
~ 200 mg
at are some risks of blood transfusions?
- transfusion-related acute lung injury
- hypervolemia
- hypocalcemia
- hypersensitivity rxn
- immune activation (bad for kidney transplant candidates)
Vitamin Supplementation in Dialysis
supplement water-soluble vitamins (B, C, and folic acid)
