IE 3: Renal Replacement Therapy

What do kidneys do? What are they a major component of?

• Filter the blood to maintain water, electrolytes, waste, and balance acids and bases

• Major component of metabolism and excretion of certain medications

What is renal failure defined as? What are the 2 types of renal failure?

• Partial or complete loss of kidney function

  • Inability to maintain fluid, electrolytes, waste or acid-base

  • Accumulation of medications renally excreted

• Two types of renal failure

  • Acute Kidney Injury (AKI)

  • Chronic Kidney Disease (CKD)

How should you treat AKI?

• Address underlying causes of AKI

• Think of possible meds responsible

• Consider external support while trying to achieve recovery of kidneys

How should you consider treating CKD?

• There is NO cure for CKD as kidneys become progressively injured and lose function over time

• Two options:

  • External support

  • Kidney transplantation

What does Renal Replacement Therapy act as?

• As an artificial kidney to replicate lost functions

  • Optimize fluid balance

  • Prevent or treat electrolyte and acid-base disturbances

  • Elimination of medications

  • Avoid hemodynamic or nephrotoxic-related kidney injury

How does dialysis work?

• Blood is pumped out of patient into blood line

• Heparin is added to prevent clotting

• Blood sent to dialyzer where excess fluids, electrolytes and wastes are removed (effluent)

• Cleaned blood is removed of air bubbles and returned to patient

How is dialyzed blood accessed by?

• Arteriovenous fistula (AVF)

• Arteriovenous graft (AVG)

• Central venous catheter (CVC)

In terms of dialysis access what is the differences in AVF, ABG, and CVC?

• AVF

  • Time to mature/use: 2-6 months

  • Maintenance: minimal

  • Infection risk: low

  • Thrombosis risk: low

• AVG

  • Time to mature/use: 2-4 weeks

  • Maintenance: frequent (patency)

  • Infection risk: medium

  • Thrombosis risk: medium

• CVC

  • Time to mature/use: immediate

  • Maintenance: frequent (exchange)

  • Infection risk: high

  • Thrombosis risk: high

What does a hemodialysis dialyzer contain? What does it remove?

• Dialyzer contains semipermeable membrane that blood passes through

• Removes solutes (waste and electrolytes) without removing important components of blood

  
  

What does a dialysate fluid contain?

• Contains electrolytes and buffer

  • Waste removal while normalizing plasma composition

Dialysis occurs through which. main ways of filtration?

• Diffusion (requires dialysate)

• Convection (requires pressurized blood)

What impacts RRT removal? What is the mode of removals?

• Molecular weight impacts RRT removal

• Mode:

  • Large molecules: convection or adsorption (nothing above 50k is cleared)

  • Middle: convection better than diffusion

  • Small: diffusion better than convection

What are the indications for RRT?

• “AEIOU”

• Acidosis/azotemia

• Electrolyte imbalance

• Intoxication/drugs

• Overload of fluids

• Uremia

What is Azotemia and when is it seen? What does it lead do and what may it progress to?

• Elevation of nitrogen waste products in blood (including urea)

  • Seen when kidney function worsens

  • Leads to elevation of BUN and SCr

• May progress to uremia (urea in blood

What are the toxic medications removed by RRT?

• Acetaminophen

• Barbiturates (phenobarbital)

• Carbamazepine

• Ethylene glycol

• Gabapentin / Pregabalin

• Lithium

• Metformin

• Methanol

• Phenytoin

• Salicylates

• Theophylline

• Valproic acid

What are the different modalities of RRT?

• Intermittent → IHD (intermittent hemodialysis), SLEDD (slow low efficiency daily dialysis)

• Continuous → CRRT (continuous renal replacement therapy)→ CVVH (continuous venovenous hemofiltration), CVVHD (continuous venovenous hemodialysis), CVVHF (continuous venovenous hemodiafiltration)

What is the duration of intermittent hemodialysis? What does it remove, what risk if made? When can it be performed?

• Shortest dialysis procedure

  • 4-6 hours

  • Performed 3 times per week

• Removes the most solute and fluid

  • Risk of hypotension

• Can be performed both inpatient and outpatient

What are the IHD (intermittent) outpatient options?

• Dialysis clinics

  • Fixed time slot

  • Availability of healthcare professionals

• Home hemodialysis

  • Option for higher frequency

  • More flexibility

    
    

What is the process of peritoneal dialysis?

• Waste products cross the semipermeable membrane into the peritoneal space with the dialysate

What is sustained low efficiency dialysis? What does it have less risk of? What is limited and who is it only performed in?

• Hybrid between IHD and CRRT

  • 6-12 hours

• Less risk of hypotension compared to IHD

• Limited drug clearance data

• Only performed in critically-ill patients

  
  

How long is continuous RRT ran over? What is characteristic of the removal of solutes and fluid? Who is it only performed in?

• Run over 24 hours

• Slower removal of solutes and fluid

  • Closer to physiologic kidney function

  • Lower risk of hypotension

• Only performed in critically-ill patients

  
  

In continuous RRT, what is the differences in CVVH, CVVHD, and CVVHDF?

• CVVH:

  • Mechanism of solute clearance → convection

  • Dialysate? → no

  • Replacement fluid? → yes

  • Solute size removed → small to large

  • Effluent → fluid removed + replacement fluid

• CVVHD:

  • Mechanism of solute clearance → diffusion

  • Dialysate? → yes

  • Replacement fluid? → no

  • Solute size removed → mostly small

  • Effluent → fluid removed + dialysate

• CVVHDF:

  • Mechanism of solute clearance → diffusion and convection

  • Dialysate? → yes

  • Replacement fluid? → yes

  • Solute size removed → small to large

  • Effluent → fluid removed + replacement fluid + dialysate

Why is replacement fluid used? What are the buffer agents?

• Replace fluids lost during CRRT

  • Containing electrolytes and buffer to return blood closer to physiologic state

• Buffer agents:

  • Lactate

  • Bicarbonate

  • Acetate

In Lactate, what does it convert to in physiologic conditions? When is it not used?

• Bicarbonate

• Not used in liver failure > lactic acidosis

In Bicarbonate, what is known about its usage? What change does it make to arterial pressure? Where is it preferred? What are the precipitation concerns?

• Most commonly used

• Little change in arterial pressure

• Preferred in liver failure

• Precipitation concerns with calcium and magnesium

In acetate, what is known about the use? What can it cause?

• Historical use, though poor control of acid-base balance

• Can cause hyperacetatemia and vasodilation

What are complications of RRT?

• Infection

• Thrombosis

• Electrolyte abnormalities

• Metabolic alkalosis

• Hemodynamic shifts

• Medication clearance

  
  

What is the infection risk in RRT? What are some signs of possible access site infection?

• Increased risk from frequent bloodstream access

• Differing risk based on access

• Signs of possible access site infection:

  • Redness or swelling of site

  • Drainage or pus along site

  • Fever

  • Chills

  • Malaise

Rank the bloodstream infection risk?

• Fistula (lowest risk) → Graft → Central Venous Catheter (highest)

When is management of infection in RRT only in?

• Only for ACUTE infection

In management of infx in RRT, what is antibiotic therapy duration?

• 4-6 weeks of therapy

• Lower duration possible

In management of infx in RRT, what is source control?

• Removal of catheter

  • Culture catheter tip

• Surgical removal of graft

WHat is a primary issue in CRRT?

• Clotting

Clotting in CRRT circuit can lead to what?

• Anemia due to blood lost in circuit

How do you minimize clotting in CRRT circuit anticoagulation and what are the options?

• Provide anticoagulation to the circuit to minimize clotting

• Options:

  • Heparin

  • Trisodium Citrate

What are advantages and disadvantages in UFH and Citrate?

• UFH: easily reversible, inexpensive → increased bleeding risk HIT

• Citrate: lower bleeding risk → hypocalcemia

In Trisodium citrate related hypocalcemia, what does it bind with? What do we need?

• Binds with calcium, forming chelated complexes

• Calcium prevented from activating clotting pathways

• Need calcium replacement

  
  

When not in use, what can happen in RRT catheter? What can prevent this?

• Clotting

• Prevented by either a saline flush or by a citrate “lock”

If occluded in RRT catheter, what can we do?

• If occluded, may instill tissue plasminogen activator (tPA; Cathflo) in catheter for 30 minutes

What is the comparison between IHD vs SLED vs CRRT?

• IHD

  • Duration → 4-6 hrs

  • Blood flow rate → >300 mL/min

  • Dialysate flow rate → 500-750 mL/min

  • Fluid removal → fluid removed + replacement fluid

• SLED

  • Duration → 6-12 hrs

  • Blood flow rate → 200 mL/min

  • Dialysate flow rate → 100-200 mL/min

  • Fluid removal → fluid removed + dialysate

• CRRT

  • Duration → 24 hrs

  • Blood flow rate → <200 mL/min

  • Dialysate flow rate → <50 mL/min

  • Fluid removal → fluid removed + replacement fluid + dialysate

Is there always requirement for long term RRT? What are reasons for stoping RRT?

• Not all patients will require long-term RRT

• Possible reasons for stopping RRT

  • Recovery of kidney function (AKI)

  • Removal of lines due to infection

  • Withdrawal of supportive measures

    
    

The clearance of meds is dependent on what?

• PK profile and size of pores in hemofilter

What causes increased medication clearances in dialysis?

• Hydrophilic

• Neutral charge (non-ionic)

• Molecular weight <500 Daltons

• Low volume of distribution

• Low protein binding

Medication clearance changes with what? What is preferred, PK dat or guideline recs?

• with worsening renal function and dialysis

• PK data>guideline recs

  • Dosing adjustments via drug databases

  • Recs per facility protocols

• Loading vs maintenance doses

• Loading doses not impacted * check recording for rest

What is vancomycin?

• A glycopeptide antibiotic used in hospital settings for management of moderate to severe infections

What is dosing based on in vancomycin? What is vancomycin typically seen with in terms of doses?

• Dosing based on trough / area under the curve (AUC) targets

• Typically seen with standing doses with regular intervals

  • Ex: q8 hours, q12 hours, q24 hours

    
    

In AKI and CKD, vancomycin’s PK profile does what? Which is more stable in clearance?

• In AKI and CKD, vancomycin's pharmacokinetic profile changes, especially in its clearance

  • CKD should have a stable clearance > able to calculate a standing dose

  • AKI (or AKI on CKD) is more unstable > spot dosing

Dosing strategies is dependent on what? In CRRT patients can use what?

• Dosing strategies will be dependent on which modality is used and whether the patient has oliguria or anuria

  • In CRRT, patient should have steady removal, can use a standing dose

For vancomycin in IHD, when do you check serum vanc levels? What is the goal serum level?

• Check serum vancomycin level before and/or after HD

• Goal serum level:

  • 20-25 prior to dialysis

  • 15-20 after dialysis

What do you calculate for vanc in IHD?

• Calculate dialysis clearance

  • Around 30-40% cleared in HD

• Calculate a dose to give

  • Based on patient's volume of distribution (Vd)

What is the volume of distribution in Vanco?

• Vd(L) ~ 0.7x Actual Body Weight (kg)

For Vanco in IHD, what is the change in serum level needed?

• Desired level (mcg/mL) – current level
  (mcg/mL

For Vanco in IHD, what is the change in serum Vanco level?

• Vanco Dose (mg) / Vd = needed change in serum level