Renal replacement therapy: Terminology

Reviewed and revised 21 November 2016

OVERVIEW

This page defines and discusses the following Renal Replacement Therapy (RRT) terminology and nomeclature:

• extracorporeal circuit
• diffusion
• ultrafiltration
• convection
• filtration fraction
• sieving coefficient
• filter or dialyser
• RRT
• continuous arterio-venous techniques
• IHD
• SCUF
• CRRT
• High volume haemofiltration
• high cut-off haemofiltration
• SLEDD
• predilution
• postdilution
• middle molecules

EXTRACORPOREAL CIRCUIT (EC)

• the path for blood flow outside the body
• vessel -> catheter -> tubing -> filter/dialyzer -> tubing -> catheter -> vessel

DIFFUSION

• Diffusion is the movement of molecules from an area of high concentration to an area of low concentration (best for small molecule clearance)
• Strictly speaking, dialysis is solute removal by diffusion of the solute across a membrane (however, in clinical settings dialysis usually means a combination of diffusion and convection)
• during dialysis the electrolyte solution (dialysate) runs in the opposite direction (countercurrent) to blood flow separated by a semi-permeable membrane.
• the rate of mass transfer/diffusion determined by:

(1) characteristic of solute (size, charge, protein binding)
(2) the dialysis membrane (type, porosity, thickness, surface area)
(3) the rate of solute delivery (blood flow rate and dialysate rate – > helps generate concentration gradient)
(4) gradient of substance in dialysate to blood

Clinical significance

• substances < 20kDa can be removed (urea, creatinine, uric acid, ions, IL-6, endotoxin, heparin, pesticides, ammonia, most protein bound drugs)
• causes less damage to platelets and leukocytes
• poorly removes larger molecules

ULTRFILTRATION

• movement of fluid through a semipermeable membrane
• a membrane’s effectiveness to ultrafiltrate fluid is described by the ultrafiltration coefficient (KUF), which is QUF/ deltaP (volume of ultrafiltrate per unit time, divided by the pressure gradient across the membrane)

CONVECTION (solvent drag)

• Convection is movement of molecules through a semipermeable membrane associated with the fluid being removed during ultrafiltration
• solute molecule is swept through a membrane by a moving stream of ultrafiltrate
• convective transport is independent of solute concentration gradients across the membrane
• porosity of the membrane determines which solutes are removed
• positive pressure is generated in the blood compartment by:

(1) increasing the hydrostatic pressure in the blood compartment
(2) increasing the rate of blood flow to the membrane

OR

• negative pressure in the dialysate compartment facilitates ultrafiltration, created by decreasing the oncotic pressure of plasma by pre-dilution

Clinical significance

• more effective method for fluid removal
• middle sized molecules (< 60 kDa) removed (ie. mediators in sepsis)
  — e.g. IL-8, TNF, IL-10, IL-6, complement, eicosanoids, platelet activating factor, myocardial depressants

FILTRATION FRACTION

• Filtration fraction is the fraction of plasma that is removed from blood during haemofiltration.
• the relationship between trans-membrane pressure and oncotic pressure determines the filtration fraction
• optimal filtration fraction at a haematocrit of 30% is 20-25%
• a higher filtration fraction can lead to a haemoconcentration in the filter increasing the risk of filter clotting

SIEVING COEFFICIENT

• Sieving coefficient is the  ratio of the concentration of solutes in the ultrafiltrate to that of plasma
• a high sieving coefficient is desirable for middle molecules but undesirable for albumin for sized molecules
  SC = 1 – describes complete permeability (for urea and creatinine)
  SC = 0 – reflects complete impermeability
  SC > 1 – requires an external energy source
• during ultrafiltration, the driving pressure forces solutes (such as urea and creatinine) against the membrane, the solutes penetrate the pores of the membrane to an extent determined by the membrane sieving co-efficient for that molecule.
• major factors determining sieving coefficient include:
  — solute molecular size
  — protein binding
  — filter porosity

FILTER or DIALYSER

• = tubular-shaped device made up of plastic casing and the capillary fibers of the semipermeable membrane with in.

RRT

• RRT is renal replacement therapy
• replacement of the function of kidneys: filtration and movement of electrolytes & fluid in and out of the body
• for all techniques fluid balance is maintained by the difference between fluid INPUT (dialysate and/or replacement fluid or both) and OUTPUT (spent dialysate and/or ultraflitrate or both)

CONTINOUS ARTERIO-VENOUS TECHNIQUES

• these include all of the CRRT techniques (haemofiltration, haemodialysis and haemodiafiltration – just change VV for AV)
• however, here the patients blood pressure drives blood through the filter which contains the highly permeable membrane
• process starts in an artery -> extracorporeal circuit -> vein
• continuous AV techniques have been abandoned in favour of continuous VV techniques

IHD

• IHD is  intermittent haemodialysis
• fluid removed by ultrafiltration (despite being called ‘dialysis’)
• solutes removed by diffusion
• blood and dialysate are circulated on the opposite sides of a semipermeable membrane in a counter current direction resulting in diffusive solute removal
• ultrafiltration can also be achieved by applying a negative pressure on the dialysate side of membrane
• massive flow rates (300-400mL/min)
• 3-4 hour per session
• these machines generate dialysate from tap water
  -> bacterial and endotoxin removal
  -> reverse osmosis with electrolyte and buffer additives

SCUF

• SCUF is slow continuous ultrafiltration
• removal of H2O through a semipermeable membrane
• low volume ultrafiltration (100-500mL/hr)
• no fluid is administered as either dialysate or replacement

CRRT

• CRRT is continuous renal replacement therapy
• extracorporeal blood purification over an extended period of time to replace kidney function

CVVH or CVVHF

• CVVH is continuous veno-venous haemofiltration
• convective dialysis + ultrafiltration
• mid sized molecules (inflammatory cytokines)
• blood driven through a highly permeable membrane by a peristalitic pump and via an extracorporeal circuit originating and terminating in a central vein.
• pressure generated induces passage of plasma water (the solvent) across the membrane (= ultrafiltration)
• as the solvent moves across the membrane it take with it many toxins (solvent drag) -> this process is called convection
• the fluid loss is replaced in part of completely with appropriate replacement fluid -> this maintains volume and electrolyte homeostasis
• flow rate: 50-200mL/min
• prescription includes; blood flow rate, replacement fluid, fluid removal rate
• fluid removal rate = effluent rate – replacement fluid + additions (anticoagulation)
• ultrafiltration rate = effluent rate

CVVHD

• CVVHD is continuous veno-venous haemodialysis
• continuous diffusive dialysis (chemical dialysis, no pressure used)
• blood on one side and dialysate on the other side flowing countercurrent
• no fluid removed because there is no ultrafiltration
• blood driven through a highly permeable membrane by a peristaltic pump and via an extracorporeal circuit originating in central vein and terminating in a central vein
• solute removal is directly proportional to the dialysate flow rate
• the fluid (dialysate) passes through the blood, molecules to which the membrane is permeable move from plasma water to dialysate
• dialysate is then discarded
• prescription; blood flow rate, effluent rate (this equals dialysate rate)

CVVHDF

• CVVHDF is continuous veno-venous haemodiafiltration
  • combines CVVH (convective dialysis) and CVVHD (diffusive dialysis)
• solute removal is achieved by a combination of convection and diffusion
• effluent is made from ultrafiltrate + dialysate
• the machine controls fluid balance by manipulating the effluent rate
• prescription includes:
  • blood flow rate
  • dialysate rate
  • replacement rate and
  • amount of fluid removal
• this is the technique used in most ICUs in Australia and New Zealand

HIGH VOLUME HAEMOFILTRATION

• goal is to remove removal of soluble mediators of sepsis
• definitions vary (e.g. >50 mL/kg/h or for very high volume HF >100 mL/kg/h)
• filtration rate – 6-10L/hr
• requires high blood flow (>300mL/min) to avoid excess predilution or excessive haemoconcentration
• hypophosphataemia can be problematic

HIGH CUT-OFF HAEMOFILTRATION

• use of special filters with larger pore size to increase CRRT’s ability to remove soluble mediators in sepsis

SLEDD

• SLEDD is sustained low efficiency daily dialysis
• hybrid therapy (intermediate between IHD and CRRT)
• advantages
  • excellent detoxification
  • haemodynamic stability
  • highly efficient
  • very flexible
  • less cumbersome machine
  • patient able to be mobilized
  • decreased requirements for anticoagulation
  • good control of volume
  • less expensive than CRRT
• disadvantages
  • high start up costs
• SLEDD is essentially the same as IHD but with reduced blood flow rates to provide less efficient clearance over a longer time period (8-12 hours)
  • blood flow rates 100-200mL/min
  • dialysate 100-300mL/min
• note that ‘low efficiency’ is compared to IHD, compared to ‘CRRT’ SLEDD is ‘high efficiency’!

PREDILUTION

• predilution is administration of the replacement fluid into patients blood before its entry into the haemofilter (prefilter delivery)
• advantages
  • increased filter life
  • improved mass transfer
  • reduces solute-membrane interactions
  • creates a concentration gradient that induces solute efflux out of RBCs into plasma
• disadvantage
  • dilutes gradient -> low efficiency -> high replacement fluid requirements to achieve solute clearance

POSTDILUTION

• postdilution is administration of replacement fluid into patient’s blood after its exit from the haemofilter (postfilter delivery)
• advantages
  • more efficient in terms of solute clearance rates (40% more)
• disadvantages
  • limited by attainable blood flow rate and associated filtration fraction constant

MIDDLE MOLECULES

• the definition of ‘middle molecue’ has changed with the advent of high flux dialysis membranes
  • originally applied to molecules larger than the small water soluble molecules that were removed by older dialysis membranes
  • European Uremic Toxin Work Group has defined the term middle molecule to be those with molecular weights between 500 Da and 60 kDa
• some middle molecules are thought to contribute to disease states such as sepsis, longterm cardiovascular disease and amyloidosis
• examples
  • middle molecules: vitamin B12, b2 microglobulin, kappa light chains
  • not middle molecules: urea, creatinine (too small); albumin (too large)

References and Links

LITFL

• CCC – RRT Indications
• CCC – RRT principles in fluid management
• CCC – RRT Types
• CCC – RRT terminology and nomenclature
• CCC – RRT troubleshooting

Journal articles

• Ficheux A, Ronco C, Brunet P, Argilés À. The ultrafiltration coefficient: this old ‘grand inconnu’ in dialysis. Nephrology, dialysis, transplantation. 30(2):204-8. 2015. [pubmed]

FOAM and web resources

• RFN — Middle Molecules