23 - CKD 2 Anemia Flashcards
KDOQI
Definition for CKD Anemia
Hemoglobin (Hb)
Males
Hb < 13.5 g/dL
Females
Hb < 12 g/dL
S/Sx of CKD Anemia
TachyCardia
- *PALE
- **Conjuctiva / palms / nail beds
Decreased MENTAL ACUITY / neurological sx
Worsening of LVH
Systolic Murmor
Fatigue / Dizziness / SOB / Palpitations / Chest Pain
Pathogenesis
CKD Anemia
Decreased Survival of RBCs / Bleeding
Erythropoietin (EPO)
normocytic & normochromic
Acute / Chronic Inflammatory Conditions
SEVERE HYPERparathyroidism
Microlytic Anemia = Iron deficiency
Macrolytic Anemia = Folic acid / vitb12 deficiency
aluminum toxicity
ESA
Use in CKD Anemia
Erythropoiesis Stimulating Agents
- *Exogenous ESA** is needed because:
- *Kidney is NO LONGER forming EPO** to stimulate RBC production in bone marrow
Glycoproteins with same biologic fxn as EPO
Reduced need for TRANSFUSION
SC or IV injections
Weight Based Dosing
When can we Initiate ESA Therapy?
KDOQI CPG
To start ESA, have to be below:
Hb < 11-12 g/dL
Goal is:
11 - 12 g/dL, not >13
we do NOT want a quick rise, due to overshooting
rate of rise:
1-2 over 1 month
When can we Initiate ESA Therapy?
FDA
To start ESA, have to be below:
Hb < 10 g/dL
Goal Followed
Goal is:
< 11 g/dL
we do NOT want a quick rise, due to overshooting
rate of rise:
< 1 g/dL over 2 weeks
ESA
ADR’s / Contraindications
BLACK BOX WARNING
use the lowest dose sufficient to reduce the need for RBC transfusion
Increased risk of: MI / stroke / VTE / VE / Tumor progression
- *Contraindications**
- *Uncontrolled HTN** / Pure Red Cell Aplasia
- Precautions: (can still start)*
- *Stroke / MI / thromboembolism / Seizures**
ESA
Dose Adjustments
Do NOT dose adjust more frequently than:
Response typically seen:
2-6 weeks
Medicare payment based on:
Hb < 12 g/dL
dose is DIFFERENT for CANCER patients
Monitor Hb:
Weekly / BI-weekly / Monthly
If hemoglobin rises quickly
= >1g/dL in 2 weeks -> may reduce ESA dose by 25%+
if >11g/dL –> reduce or hold dose
If Hb does NOT respond by
>1g/dL in 4 weeks –> increase dose by 25%
response is typically seen over 12 weeks, if no response unlikely to improve
Darbepoetin
ESA - Aranesp
Half Life + Dose
Half-Life
21hr IV // 46hr SC
Dose
0.45 mcg/kg qweekor 0.75mcg/kg q2weeks
For non-dialysis:
0.45 mcg/kg q4 weeks
Methoxy Polyethylene Glycol-Epoetin Beta
ESA - Mircera
Half Life + Dose
Half-Life
134 - 139 H
Dose
0.6 mcg/kg q2 weeks
until Hb stable then double dose qmonth
ONCE EVERY 2 WEEKS
Epoetin Alfa
ESA - Epogen / ProCrit
Half Life + Dose
Half-Life
8.5hr IV // 24hr SC
Dose
50-100 units/kg TIW
THREE TIMES A WEEK
ESA Dose Conversions
Epoetin Alfa = 3x a Week
so, converting to Darbepoetin = Weekly
need to convert accordingly
Also:
Micera is every 2 weeks or every 1 month
Causes for ESA RESISTANCE
**_IRON DEFICIENCY_** #1 cause, should be **iron replete b4 starting ESA**
Inflammation / Infxn
CKD = stage of chronic inflammation
HYPERparathyroidism
Folic Acid + VitB12 Deficiency
Chronic Blood loss / Malnutrtion / Alminum toxicity / Inadequate Dialysis
Cancer + ESA Considerations
INCREASED RISK
of cancer spreading / tumor increase / recurrance
WAIT 5 YEARS to be CANCER FREE
b4 starting ESA
Hepcidin Function
Peptide made in liver that REGULATES:
Intestinal FE absorption / Recycling / Mobilization from hepatic stores
CONTRIBUTES TO ANEMIA in CKD (BAD)
when inflammation / Infection present
- *Hepcidin –> binds to Ferroportin** in macrophages
- INHIBITS Fe Availability*
basis for most:
“anemia of chronic disease”
TSAT
Percentage Transferrin Saturation
TSAT = ( Serum Fe / TIBC ) x 100
Goal is 20-50% for all stages
TIBC > 200
for an accurate TSAT
Serum Iron
Serum Fe
Concentration of Fe bound to Transferrin
affected by inflammation & infection
Diurnal Effect
TIBC
TIBC = Total Iron Binding Capacity
Capacity of the blood
to BIND iron WITHOUTTransferrin
Should be >200 to get an accurate TSAT
KDIGO
Iron Goals
TSAT / Ferritin
Measure iron status q3months during ESA therapy
STILL ON TRIAL
if we want to increase Hb +/- decrease dose of ESA if on ESA
TSAT
< 30%
Ferritin
< 500
KDOQI
Iron Goals
TSAT / Ferritin
TSAT
> 20% for all stages
Ferritin
> 200 ng/mL HemoDialysis
> 100 ng/mL non-dialysis or peritoneal
Ferritin
- *Amount of Fe** STORED in the:
- *liver / spleen / bone marrow cells**
- *SPECIFIC for Fe DEFICIENCY**
- WHEN LOW*
High Ferritin =/= does NOT mean Iron EXCESS
since it is an Acute Phase reactant (elevated in infxn/inflmation)
Hemodialysis CKD > 200 ng/mL
non HD CKD > 100 ng/mL
200-2000 = iron + inflmattion
Iron Deficiency Anemia
#1 Cause of Anemia Worldwide
PRIMARY CAUSE OF ESA RESISTANCE
if not getting desired respnse from ESAs
Deficiency is dependent on:
- *Increased Demand / hematopoiesis
- increased loss/decreased intake or absorption***
Oral Iron
TAKE ON EMPTY STOMACH
200mg of ELEMENTAL Fe QD
divide into several doses daily
Start small –> titrate up slowly
ADR:
Fecal Discoloration / NVD / constipation
Treat for 3-6 months
Ferric Citrate
Auryxia
PHOSPHORUS BINDER** & **IRON SUPPLEMENT
Shown to:
- *Improve TSAT** + Ferritin Levels
- can lead to a decrease IRON use*
FDA Approved for:
Iron Deficiency ANEMIA in CKD non-dialysis patients
1g TID w/ meals
max 12g/day
Oral Iron
DRUG INTERACTIONS
DECREASED absorption of IRON
PPI / H2 Blockers / Cholestyramine
Antacids / Calcium / PHOS Binders
Tetracycline / Doxycycline
AFFECTED by IRON –> 2 hours
Levothyroxine
Fluoroquinolones / Mycophenolate
Tetracycline / doxycycline
IV Iron
Indication / Treatment
Given when PO canNOT be given
malabsorption / blood loss / DIALYSIS PATIENTS
Dialysis already very IRON DEFICIENT
PO can NOT meed the demands
Bolus Treatments (1gm) –> reach TSAT levels
then periodic maintenance doses
Ferric Fe3+ available in IV formulations
DO NOT GIVE DURING ACTIVE INFECTIONS
Which IV IRON
can NOT be given during DIALYSIS?
FERRIC CARBOXYMALTOSE
injectafer
ONLY FOR NON-DIALYSIS
Which IV IRON
Requires a TEST DOSE?
IRON DEXTRAN
due to anaphylaxis, also BBW
2 Brands that are NOT interchangable
Ferumoxytol
also has anaphylactic reactions
also needs to be given as a diluted product
Which IV IRON
MUST BE DILUTED?
- *FERUMOXYTOL**
- *BBW**, can also have anaphylaxis
IVPB –> infused over 15 minutes
monitor for 30 min post infusion / 1 hour of dialysis b4 admin
Contrainidicated with H/O Allergic RXN to ANY IV IRON
MRI caution
Which IV IRON
Is ADDED TO DIALYSIS SOLUTION?
FERRIC PYROPHOSPHATE CITRATE
Triferic, HD only
Delivers 5-7mg fe with EACH treatment
(dialysis removes the same amount)
ADR:
HypoTension / HA / muscle spasms / peripeheral edema
Which IV Iron
Has DELAYED ADRs 1-2 days post dose?
Arthralgia / backache / chills / dizziness
Fever / HA / malaise / myalgia / N/V
IRON DEXTRAN
IM / IVP / IVPB diluted
Requires TEST DOSE (anaphylaxis) BBW
2 brand products are NOT interchangable
MACROlytic Anemia
VITAMIN B12 + FOLIC Acid deficiency
causes
Immature LARGE RBCs
- *MCV > 100 fL**
- inadequate INTAKE + decreased ABSORPTION*
Low b12 <150 pg/mL + low folic acid <7 nmol/L
- *MMA is specific for B12 deficiency**
- may also measure homocysteine*
MACROcytic Anemia
TREATMENT
- *Vitamin B12**
- *PO: 1-2mg of cobalamin QD**
- *IM: 1000mcg qd f1week -> weekly 1 month –> qmonth**
- *Folic Acid**
- *1mg QD**
Reticulocytosis begins within 1st week
VV
bone marrow becomes normoblastin in several days
VVV
Hb rises and normalizes in 1-2 months
TRANSFUSIONS
LAST LINE
given in acute situations / cardiac instability / when you can NOT alleviate blood loss quickly
many RISKS
bacterial / paracitic infections
Iron OVERload / CITRATE toxicity
Increase ALLOANTIGEN SENSITIZATION
prolong time to recieve transplant / risk of reejection
