CKD - anemia Flashcards
CKD anaemia - Aetiology
1) decrease RBC production
- lower erythropoeitin production by kidney
- inhibitor of erythropoeisis (lower erythropoeitin production, increase uremic toxin accumulation)
- hyperparathyroidism = bone marrow fibrosis
- nutritional deficiency (Fe, folate, vit B12)
2) decrease RBC survival
. haemolysis
- abnormal RBC membrane, decrease RBC lifespan (60 vs 120 day)
- increase PTH = increase RBC osmotic fragility
- splenomegaly = increase RBC breakdown & removal
- metabolic deficiency: increase susceptibility of RBC to physiologically generated peroxides
. increase RBC loss
- GI bleed, dialysis, excessive blood draws
CKD anaemia - Lab values
1) definition
- male: Hgb < 13g/dL
- female: Hgb < 12 g/dL (lower cuz menstrual loss)
2) complete blood count (CBC)
- lower Hgb & reticulocyte count
3) Fe panel
- MCV: mean corpuscle value
- MCHC: mean corpuscle Hgb concentraion
- Fe deficiency: microcystic/hypochromic: lower Hgb & MCV & MCHC
- Vit B12/folate deficiency: macrocystic: increase MCV & MCHC
- anaemia of chronic disease: normocystic/normochromic: lower Hgb but normal MCV & MCHC
CKD anaemia - clinical presentation
- mild/mod kidney failure no severe anaemia (compensated by other body sys (CVS, respi) to maintain normal body function)
- progression into severe kidney failure partly because of anaemia (SOB, weak, loss appetite, fatigue)
- affect QoL: SOB, weak, tired, fatigue, loss of appetite, feel cold, pale
CKD anaemia - goals of therapy
- increase RBC O2 carrying capacity
- decrease symp (dyspnoea, orthopnoea, fatigue)
- prevent long term complication (increase risk of stroke/MI)
- lab values: Hgb 10-11.5 but < 13 g/dL | TSAT 20-30% | serum ferritin 200-500 (HD) 100 (non-HD)
CKD anaemia - Fe deficiency - causes
1) bleeding, malnutrition
2) ESA use = increase Fe demand
- absolute Fe deficiency: low TSAT, low ferritin
- functional Fe deficiency: low TSAT, high ferritin (high Fe store but not released fast enough to meet demands of erythropoesis, maybe high cuz of infection/inflammation)
CKD anaemia - Fe deficiency - assess Fe status
Fe panel
1) TSAT
- indicator of amt of Fe immediately avail to be delivered to bone marrow
- TSAT = (serum Fe/TIBC) x 100%
2) serum ferritin
- indirect indicator of Fe store
- acute phase reactant
CKD anaemia - Fe deficiency - oral supplement
. most convenient, non-dialysis/PD patient
. types of preparation: ferrous gluconate (12%), iron polymaltose (100%)
. daily dose 200mg divided into 2-3 dose
. best absorbed wo food/meds
. limitations
- poor absorption
- GI SE: N, C, abdominal cramp, dark stool
- poor adherence cuz of GI SE
. CI: Ca salt, quinolone, H2RA, PPi (affect absorption)
CKD anemia - Fe deficiency - IV supplement
. Indication
- increase ESA efficacy & reduce ESA dose to achieve + maintain Hgb lvl in HD patient
- pre-dialysis/PD patient
. Types of preparation
- Iron sucrose
- Ferric carboxymaltose (form stable complex, reduce risk of oxidative stress, release Fe slowly, reduce dose)
. Loading dose
- Iron sucrose (Venofer): 100-200mg IV/HD session about 5-10 dose
- max 1g/month to prevent oxidative stress
. Maintenance dose
- 100-200mg IV/month
. AE
- allergy, hypotension, dyspnoea, HA, lower back pain, arthralgia, syncope, arthritis, dizzy
- anaphylaxis
- anaphylactoid rxn (similar to anaphylaxis but not IgE mediated, Ab production w Fe dextran, CVS collapse/respi complication)
- Fe overload (hepatic/pancreatic/CVS dysfunction, monitor Fe panel before initiation, managed by desferroxamine [Fe chelating agent])
- increase risk of infection cuz IV Fe good source of nutrient for bacteria
- increase rate of atherosclerosis, CVS complication
CKD anaemia - Fe deficiency - Transfusion
- last line
- indication: low Hgb, severe blood loss + Severe anemia symp
- prevent inadequate tissue oxygenation + heart failure
- risk: infection, Fe/fluid overload, impair bone marrow RBC synthesis func
- not for patient who identified donor for kidney transplant because maybe rejection
CKD anaemia - erythropoetin
- glycoprotein cytokine produced by kidney (renal peritubule, fibro-blast like cell) in response to hypoxia to increase RBC production
- MOA
1) increase erythropoeisis in bone marrow
2) act on EPO receptor on erythroid progenitor cell to commit to differentiating & proliferating - organic chem potion
. heavily glycosylated
. 4 glycosylation site: 3 N-linked, 1 O-linked oligosaccharide chain attached to Asn and Ser residue respectively
2 internal disulfide linkages between cysteine molecules
. N-linked and O-linked: terminal -ve charge sialic acid, glycosylation site on 1 end away from EPO binding site, only N-link contribute to biological activity & t 1/2
CKD 0 anaemia - EPA
- recombinant, not endogenous
- action
1) stimulate erythropoeisis
2) increase release of reticulocyte - indication
1) non HD: Hgb < 10
2) HD: Hgb 9-10, Hgb cannot < 9
3) anaemia cuz of chronic renal failure
4) chemotherapy, bone marrow transplant, surgery - caution if hist of malignancy
CKD anaemia - Epoetin alfa (Eprex), Epoetin Beta (Recormon)
. SC: more convenient, less freq dosing, F 20-50% so higher physiologic exposure
. IV: more common, more costly, higher risk of pure cell aplasia
. dosing
1) Eprex
- non HD: 50-100 unit/kg 3x/wk SC
- HD: 50-100 unit/kg 3x/wk IV
2) Recormon
- non HD: 20 unit/kg 1-3x/wk SC
- HD: 40 unit/kg 3x/wk SC or IV
. onset 7-10 day, t 1/2 4-13h, peak conc 5-24h
CKD anaemia - Darbopoetin
- additional 2 N-linked side chain = higher MW
- longer t1/2, extended biological activity
- less freq dosing = increase compliance
- dosing
1) 0.45 mcg/kg every wk
2) 0.75 mcg/kg every 2 wk - onset 2-6 wk, peak conc 34h
CKD anaemia - Miscera
- methoxy polyethylene glycol-epoetin beta
- higher in vivo activity, longer t1/2
- more costly
- dosing
1) 0.6 mcg/kg every 2 wk
2) if stable: increase dosing interval: 1.2 mcg/kg every 4 wk - onset 5-6 wk, peak conc 72h
CKD anaemia - consideration for ESA
- 10 days for erythroid to mature & release
- refrigerated, protected from light
- monitor over time
- caution for active/hist/risk of malignancies (cancer): ESA tumorigenic, promote angiogenesis
