443 exam 3

• Treatment for anemia in CKD

  • Iron PO (for iron deficiency)
  • Iron IV (for iron deficiency)
  • ESAs
  • HIF PHI
  • RBC transfusion
• Causes of anemia in CKD

  • Blood loss for lab tests, especially when hospitalized
  • Blood losses associated with the HD procedure
  • Reduced intestinal iron absorption
  • Increased hepcidin levels
  • Interacting medications (PPIs, Ca-containing phosphate binders)
  • Reduced intake due to poor appetite, malnutrition, and diet
  • Decreased erythropoietin production
  • Uremic toxins → chronic inflammation
  • inflammation/infection → reduced iron release from body stores
• Hematology values


  • Red blood cell (RBC) count
  • Hematocrit (Hct)
  • Hemoglobin (Hgb) male 14-17, female 12-15
  • Reticulocyte count
  • Mean corpuscular volume (MCV) 80-90 - average volume and size of RBC
  • Serum iron (Fe) male 45-160, female 30-160
  • Ferritin (iron stores) male 20-250, female 10-150
  • Total iron binding capacity (TIBC) 220-420
  • Transferrin sat (Tsat) 30-50%

  
• Iron deficiency anemia


  Patients with advanced CKD will have both iron deficiency anemia and anemia of chronic disease

  
• When to initiate iron

  • Tsat (%) - <30
  • Ferritin (ng/mL) - <500
• Routine use of iron in patients with TSAT >30% or ferritin >500 ng/mLL not recommended; generally avoid IV iron in patients with active systemic infection
• Recommendations on iron administration

  • Dialysis (HD and PD) - IV iron therapy preferred
  • Not on dialysis (ND) - Reasonable to try PO iron first. If the goals of iron supplementation are not met with a 1–3 months, consider IV route
• Oral iron preparations - clinical pearls

  • Common adverse effects: Nausea, constipation, abdominal pain, stool darkening
  • Absorption increased by empty stomach, vitamin C
  • Drug interactions - Drugs that raise gastric pH (H2A, PPIs), Drugs and foods that contain Calcium, Quinolone and tetracycline antibiotics, Levothyroxine, Bisphosphonates, etc... - separate by at least 2 hours
• IV iron preparations - considerations

  • Anaphylactic reactions (rare)
  • Hypotension, syncope → Decrease rate of infusion
  • MRI interference for up to 3 months (ferumoxytol only)

  
• Erythropoietin-stimulating agents (ESAs)


  • Indicated for patients with anemia of chronic disease due to insufficient production of erythropoietin
  • Mechanism of action - Same biologic activity as endogenous erythropoietin → bind to and activate the erythropoietin receptor to stimulate erythropoiesis
  • Formulations - Epoetin alfa, Epoietin alfa-epbx, Darbepoetin alfa, Methoxy-PEG Epoietin beta
• Epoetin alfa starting dose and route of administration

  • Starting dose recommended by FDA for DIALYSIS patients - 50-100 units/kg IV/SQ three times weekly
  • Subcutaneous → preferred in CKD-ND or CKD-5PD
  • Intravenous (IV) → preferred in CKD-5HD

  
• ESA dose adjustments


  • Do not increase ESA dose more frequently than once every 4 weeks. Decreases in dose can occur more frequently but try to avoid frequent dose adjustments.
  • If hgb rises rapidly (> 1 g/dL in a 2-week period or >2 g/dL in one month), reduce the dose by ~25% (or more as needed). Hold ESA If Hgb >13 g/dL.
  • If hgb does not increase >1 g/dL after 4 weeks of therapy, increase dose by ~25%.
• FDA Black Box warning → ESAs INCREASE THE RISK OF DEATH, MYOCARDIAL INFARCTION, STROKE, VENOUS THROMBOEMBOLISM, THROMBOSIS OF VASCULAR ACCESS AND TUMOR PROGRESSION OR RECURRENCE
• ESA contraindications


  • Uncontrolled hypertension
  • Pure red cell aplasia (PRCA) (rare)

  
• When to initiate ESA

  • In CKD-ND, initiate ESA in hgb < 10 g/dL
  • In CKD-5PD initiate ESA when hgb 9-10 g/dL
  • Avoid hgb > 11.5 g/dL unless improvement in QoL, always avoid hgb > 13 g/dL in all patients
• Hemoglobin targets & ESA dosing

  • Start ESA if hgb <10 g/dL AND other causes of anemia are excluded
  • General hgb target is 10-11.5 g/dL
  • In general, do not use ESAs to maintain hgb concentration >11.5 g/dl
  • Never use ESAs to increase hgb >13 g/dl
  • Monitor hgb at least monthly during initiation phase, then either every 3 months if CKD-ND or monthly if CKD-5D

  
• Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF PHIs)

  • FDA approved Feb 2023 for anemia of CKD in dialysis patients
  • Mechanism of action - By preventing hydroxylation of HIF-α, PHIs prevent its degradation and stabilize the HIF-α/HIF-β heterodimer → Increased erythropoiesis, Hgb, Decreased hepcidin levels
• HIF PHI dosing


  • Dose depends on the Hgb levels (1-4 mg PO qday)
  • Do not increase more frequently than every 4 weeks
  • If Hb increases rapidly (eg, >1 g/dL over 2 weeks or >2 g/dL over 4 weeks) → Decrease dose.
  • If Hb >11 g/dL → Decrease dose.
  • If Hb >12 g/dL → Hold drug
• HIF PHIs have a black box warning for increased risk of death, MI, stroke, venous thromboembolism, and thrombosis of vascular access
• The most commonly used treatment for ESRD is hemodialysis
• Basic principles of dialysis

  • Diffusion - Movement of small molecules (<500 Da) along a concentration gradient
  • Ultrafiltration - Movement of water across membrane
  • Convection - Movement of solutes along with water as pressure is applied

  
• Hemodialysis (HD)


  • Method of fluid removal: Diffusion + convection
  • Patient population - CKD Stage V – lifelong unless transplant, Emergent HD in AKI – (usually) temporary
  • Options for treatment - Hemodialysis clinic, Home hemodialysis, Hospital

  
• Hemodialysis access


  AV fistula = surgical connection between artery & vein, Causes extra pressure

  
• Basic principles of dialysis

  • Diffusion - movement of small molecules along a concentration gradient, main mechanism for removing urea & creatinine
  • Ultrafiltration - movement of water across membrane, used mainly to remove excessive fluid
  • Convection - movement of solutes along with water as pressure is applied, allows movement of mid-large molecular weight particles

  
• Hemodialysis (HD)


  Method of fluid removal: Diffusion + convection
• Patient population for hemodialysis


  • CKD Stage V - lifelong unless transplant
  • Emergent HD in AKI - (usually) temporary
• Options for hemodialysis treatment

  • Hemodialysis clinic - usually tiw (MWF vs. TTS) - most common
  • Home hemodialysis - usually 5-6 times weekly
  • Hospital
• Types of hemodialysis access

  • AV fistula - surgical connection between artery & vein
  • AV graft - synthetic graft that connects vein & artery
  • Central venous catheter

  
• AV fistula


  • Causes extra pressure & extra blood to flow into the vein → grows larger/stronger, preferred over other types of access → good blood flow for dialysis, lasts longer than other types of access, & less likely to get infected/clot, 1-2 months to mature before use

  
• AV graft


  • Take 2-3 weeks before they can be used, higher risk of complications & lower survival compared to fistulas, difficult to remove
• Central venous catheter


  • Can be used immediately, highest rate of complications & shortest survival
• Common complications of hemodialysis

  • Hypotension (fluid removed too much/fast)
  • Catheter infection
  • Catheter thrombosis
  • Vitamin deficiency (due to removal of water-soluble vitamins via HD)

  
• Hypotension (fluid removed too much/fast)

  Treatment → bolus of NS (100-250 mL) or hypertonic (23.4% saline (10-20 mL) or albumin (5%); reduce ultrafiltration rate, Prevention → longer HD sessions, omit antihypertensives on dialysis days, Midodrine, Droxidopa
• Catheter infection


  Antibiotics, catheter removal
• Catheter thrombosis


  Treatment → intraluminal alteplase, intraluminal reteplase

  
• Vitamin deficiency (due to removal of water-soluble vitamins via HD)


  All HD patients require supplementation w/ water-soluble vitamins (i.e. Nephplex, Nephro-vite, etc.), Regular multivitamins are not recommended
• Peritoneal dialysis (PD)


  Peritoneal cavity serves as a dialysate compartment, Peritoneal membrane lining the abdominal cavity serves as semi-permeable membrane → diffusion (mainly) + ultrafiltration

  
• Types of peritoneal dialysis

  • Continuous ambulatory peritoneal dialysis (CAPD) - patient performs the prescribed number of dialysate exchanges manually
  • Automated peritoneal dialysis (APD) - includes an automated cycler that performs the exchanges, the machine performs several short-dwell exchanges (1-2 hours for improved efficiency) during the night

  
• Peritoneal dialysis complications


  • Glucose load/hyperglycemia – dextrose used as hyperosmolar agents to induce ultrafiltration
  • Peritonitis – cloudy effluent +/- abdominal pain
  • Catheter infection – purulent drainage at the exit site

  
• Glucose load/hyperglycemia


  IP insulin (added to the PD bag), switch to a glucose polymer (icodextrin)