IPC Kidney: Anemia in CKD (Week 3)

anemia in CKD definition for males

HGB <13 g/dL

anemia in CKD definition for females

HGB <12 g/dL

how do tissues normally become oxygenated?

kidney releases erythropoietin, which stimulates bone marrow to release hemopoietic stem cells, which become red blood cells, which oxygenate tissues

how does tissue oxygenation decrease?

when tissues are oxygenated by RBCs, this signals the kidney to decrease production of erythropoietin causing a negative feedback loop

what are the 5 factors that decrease oxygenation?

low blood volume, anemia, low hemoglobin, poor blood flow, pulmonary disease

what are the 4 goals of therapy for anemia of CKD?

1. increase oxygenation-carrying capacity

2. improve quality of life

3. prevent/alleviate symptoms and complications of anemia

4. decrease need for blood transfusions

why do we try to decrease the need for blood transfusions in pts with anemia of CKD?

these pts will eventually need kidney transplants, the immune response to kidney transplant increases each time a pt receives a blood transfusion

how do blood transfusions increase the immune response in CKD pts? how does this impact future kidney transplants?

increased number of blood transfusions increases the number of immunogenic stimuli = more reactive immune system to subsequent kidney transplant

what are reticulocytes?

immature RBCs

how does the kidney return to homeostasis after a period of decreased oxygen delivery to the kidneys?

peritubular interstitial cells detect low oxygen levels in the blood, these cells secrete erythropoietin into the blood, proerythroblasts in red bone marrow mature more quickly into reticulocytes, more reticulocytes enter circulating blood, larger number of RBCs in circulation increase oxygen delivery to tissues

what type of cells detect low oxygen levels in the blood and secrete erythropoietin?

peritubular interstitial cells of the kidney

without ___, we cannot form functional hemoglobin

iron

during good health, ___% of circulating erythropoietin is produced in the ___ with a minor component made in the ___

90, kidney, liver

EPO stimulates the ..... in response to hypoxia

proliferation and differentiation of erythroid progenitor cells

during CKD anemia, what is the RBC life span? what is the normal RBC life span?

CKD: 60 days (dialysis), normal: 120 days

anemia begins to develop as GFR declines to ___

<45 ml/min/1.73m^2

what stages of CKD can anemia begin to develop?

stage G3b and beyond

if a CKD pt with anemia has an iron deficiency, what type of anemia do they have?

microcytic anemia

if a CKD pt with anemia has a folate or B12 deficiency, what type of anemia do they have?

macrocytic anemia

what is the typical type of anemia seen in CKD pts?

normochromic normocytic anemia

what is the normal range for RBC count in males?

4.5-5.9 x 10^6 cells/mcl

what is the normal range for RBC count in females?

4.1-5.1 x 10^6 cells/mcl

what is the target range for RBC count in anemia of CKD?

within normal limits

what is the normal range for hemoglobin in males?

14-17.5 g/dL

what is the normal range for hemoglobin in females?

12.3-15.3 g/dL

what is the target range for hemoglobin in anemia of CKD?

10-11 g/dL

what does hemoglobin mean?

oxygen carrying capacity of RBCs

what is the normal range for hematocrit in males?

42-50%

what is the normal range for hematocrit in females?

36-45%

what is the target range for hematocrit in anemia of CKD?

30-33%

what does hematocrit mean?

percent of blood volume occupied by RBCs

what is the normal range for mean cell volume (MCV) in both males and females?

80-96 fL/cell

what is the target range for mean cell volume (MCV) in anemia of CKD?

within normal limits

what does mean cell volume mean?

average size of RBCs

mean cell volume ___ in iron deficiency

decreases

what is the normal reticulocyte count in both males and females?

0.5-2.5% of RBCs

what is the target range for reticulocyte count in anemia of CKD?

>2.5%

an increased reticulocycte count reflects...

production of RBCs (erythropoiesis)

what is the normal range of serum iron?

50-150 mcg/dL

what is the target range of serum iron?

within normal limits

what does serum iron mean?

iron bound to transferrin

what is the normal range of serum ferritin?

>10-30 ng/mL

what is the target range of serum ferritin?

>500 ng/mL

what does serum ferritin mean?

storage form of iron

what is the normal range of total iron binding capacity?

250-410 mcg/dL

what is the target range of total iron binding capacity?

within normal limits

what does total iron binding capacity mean?

capacity of transferrin to bind to iron

what is the normal range of transferrin saturation in males?

15-50%

what is the normal range of transferrin saturation in females?

12-45%

what is the target range of transferrin saturation?

>30%

what does transferrin saturation mean?

reflects iron available for immediate erythropoiesis

iron is an essential factor in the ___

biosynthesis of hemoglobin

too much free iron can cause ___

cellular damage

where in the body is iron stored as ferritin?

liver

what are 4 causes of iron loss?

sloughed mucosal cells, desquamation, menstruation, other blood loss

which transporter allows for iron uptake?

divalent metal transporter 1 (DMT1)

when is hepcidin normally released?

in states of high iron absorption/exposure, protects body from iron overload

how does hepcidin protect the body from iron overload?

shuts down ferroportin, therfore iron cannot get out of the cell

which cell types are iron-exporting cells?

duodenal enterocytes, macrophages, hepatocytes

what effect does low hepcidin have on iron?

uptake of iron into the cell as ferritin, ferroportin transport protein then releases iron into the plasma

when iron is released into the plasma...

it can bind to transferrin and stimulate bone marrow to produce RBCs

what effect does high hepcidin have on iron?

iron uptake as ferritin into the cell, ferroportin is blocked by hepcidin to block iron release into the plasma

___ is the most common cause of erythropoietin resistance

iron deficiency

we must correct ___ first, to use erythropoietin such that hemoglobin is adequate and included in RBCs

iron deficiency

iron panel should be monitored ___ in a dialysis pt or anyone receiving ESA for anemia

every 3 months

what is the therapeutic response to iron?

increased reticulocyte count within 7-14 days, increased hemoglobin and hematocrit within 3-4 weeks

what are the goals of iron therapy in CKD?

TSat >30%, serum ferritin >500 ng/mL

due to the risk of ___, IV iron should be held for TSat > ___ or Ferritin > ___

iron overload, 50%, 1200 ng/mL

check hemoglobin and hematocrit ___ during iron therapy

weekly

check TSat and serum ferritin every ___ during iron therapy

3 months

oral iron should be taken ... to increase absorption

on an empty stomach

what are some characteristics of oral iron therapy?

poor absorption, GI complications, poor adherence, inexpensive, slow replenishment of iron stores

what are some ADRs of oral iron therapy?

GI complications: nausea, constipation, cramping; dark stool; many DDIs

what are some characteristics of parenteral iron therapy?

expensive, better absorption, rapid replenishment of iron stores, risk of iron overload, infusion reactions, anaphylactic reactions

what type of reaction can occur with parenteral iron therapy?

anaphylactic (SOB, chest pain, hives)

avoid ___ use of parenteral iron, why?

IM, it has variable absorption/painful/bleeding risk

what are some common ADRs of IV iron therapy?

hypotension, flushing, edema

what are more rare ADRs of IV iron therapy?

dyspnea/wheezing, itching, myalgias, chest pain, cardiac arrest, injection site rxn, anaphylactoid and anaphylactic rxns

if pt has ____ do NOT give IV iron

an active systemic infection

why can't we give IV iron to pts with active systemic infections?

iron is like a food for bacteria and can also inhibit some of our WBC trafficking towards the site of infection (inhibits chemotaxis of neutrophils)

can you give IV iron to pts with skin infections or UTIs?

yes, these are superficial infections not systemic

what % elemental iron is ferrous sulfate?

20

what % elemental iron is ferrous sulfate ER?

20

what % elemental iron is ferrous fumarate?

33

what % elemental iron is ferrous gluconate?

12

what % elemental iron is polysaccharide iron?

100

what % elemental iron is ferric maltol?

100

what % elemental iron is ferric citrate?

100

what is the brand name of ferric maltol?

accrufer

what is the brand name of ferric citrate?

auryxia

for traditional oral iron agents, oral bioavailability is...

10-15% regardless of salt form

what is traditional dosing of oral iron therapy?

target 200mg elemental iron/day in divided doses

newer oral iron agents appear to have better...

bioavailability and tolerability

administer oral iron therapy ___ before food

1 hour

what is the alternative oral iron dosing regimen?

once daily or once every other day

what are the benefits of alternative (QD/QOD) oral iron dosing?

decreases rise in hepcidin, increases relative bioavailability, may improve compliance and/or reduce GI adverse effects

alternative oral iron dosing regimens have NOT been studied in ___

CKD pts-- good from ADR/compliance perspective, but may not give enough iron for CKD pts

what are drugs that decrease iron absorption?

Al/Mg/Ca containing antacids, tetracyclines, H2 antagonists, PPIs, cholestyramine

why do drugs such as antacids, PPIs, and H2Ras decrease iron absorption?

due to iron needing an acidic environment to be absorbed

what are some object drugs affected by iron?

fluoroquinolones, levothyroxine, tetracyclines, mycophenolate, methyldopa, levodopa