Separation Technology in Dialysis

Allan P. Turner M.D.

February 17,2006

Kidney Function

Kidney Function

Terms Used in Dialysis

• Diffusion

• Convection

• Ultrafiltration

• Clearance 100 ml/min100mg/dl

100 ml/min50 mg/dl

Clearance=50 ml/min

100 ml/min100mg/dl

100 ml/min10 mg/dl

Clearance=90 ml/min

Options for RRT• Hemodialysis

– 3X a week for 3-4 hours– diffusive clearance with ultrafiltration of water– faster blood flow rates=less hemodynamic stability

• CRRT(Hemodiafiltration)– a continuous process– used on critically ill patients in US– more convective clearance– lower blood flow rates and smaller filter=greater hemodynamic

stability

• Peritoneal Dialysis– peritoneal membrane used as semipermeable membrane– batch process

Description of Hemodialysis

• Primarily diffusion

• Dialysate– looks like blood of

healthy patient

• 3X week for 3-4 hours

• Blood and dialysate flows are fast– QB=500 ml/min

– QD=800 ml/min

Membrane(Dialyzer)

• Hollow Fiber Design

• Biologic vs synthetic

• Reuse

• Terms– Biocompatibility– High efficiency– High flux

Access

• Difficult

• Trade Offs– rapidity of use

– chance of infection

– patient comfort

– need for addl procedures

Access(PermCath)

• Use immediately

• No needle sticks

• High infection rate

• High recirculation

Access(AV Graft)

• Use in 2-3 weeks• Some infection

risk• 2 needle sticks• low recirculation• numerous

interventions to keep open

Access(AV Fistula)

• 3-18 months to use

• Minimal infection risk

• Can last a lifetime

Anticoagulation• Blood clots

• Heparin – discovered in 1926

• Partial clotting– limits diffusion

• reduces surface area

• Access must stop bleeding

• Calcium– required for clotting

Dialysis Machine

• Blood Circuit– anticoagulate

– deliver blood to membrane

– safely return blood to patient

• Dialysate Circuit– deliver dialysate at proper

temperature, concentration, and pH

– control ultrafiltration

Dialysis Machine(Blood Circuit)

• Roller pump• Heparin syringe

pump• 2 air traps• Air detector• Venous line clamp

Dialysis Machine(Dialysate Circuit)

• Warm, deaerate, mix concentrates, monitor conductivity and pH, pump

• Detect blood leaks

• Generate and monitor ultrafiltration

Dialysis Machine

Dialysis Machine

Dialysate

Urea Clearance

• ?Urea = uremic toxin?

• Diffusion

• Urea: MW=60 (small)

• KoA

• Clearance of urea of 250ml/min

• Native kidneys provide urea clearance of about 90-110ml/min

Urea Clearance

Clearance of Other Solutes• Urea(MW 60), creatinine(MW 113), B12 (MW=1355), ß2

microglobulin (MW=11,800), albumin (MW=80,000)

• Middle molecules

• Diffusion not effective

Hemofiltration• Convection to clear

larger molecules

• Replacement fluids without removed solute

• Costly

Continuous Renal Replacement Therapy(CRRT)

• Critically ill ICU patients– low BP

– can’t tolerate large QB or large filter

– often can’t be systemically anticoagulated

• Continuous– low clearances but runs 24/7

• Anticoagulation– regional anticoagulation instead of systemic

• Combine hemodialysis and hemofiltration– hemodiafiltration

– increases clearances even of middle molecules

– continuous venovenous hemodiafiltration(CVVHDF)

CRRT vs Hemodialysis

QB

150ml/hrDialysate + Ultrafiltration +Replacement fluid

Replacement fluid1000ml/hr

Dialysate40ml/min(2500ml/hr)

QB

500ml/hr

Dialysate + Ultrafiltration

CRRT

HemodialysisDialysate800ml/min(48,000ml/hr)

CRRT Citrate Anticoagulation

DIALYZER

BloodFrompatient

BloodTopatient

C CC CC C

Calcium C

CC

C C

C

CCC

LiverCitrate HCO3

Tri-Sodium Citrate

CRRT

V

QB

QE = QR + QFR + QD

Dialysate: 4 L bag Na+ 140 mEq/L

Cl- 118.5 mEq/L

HCO3 25 mEq/L

K+ 4.0 mEq/L

Mg 1.16 mEql/L

Rate: 1000-2500 mL/hr

QD

100-150 mL/min

(actual QB = QB, machine – QR)

Patient

Ca2+ Gluconate

78 mEq /L (20 g/L) in NS

Rate: 80 mL /hr

PF iCa 2+ (0.25-0.5 mmol /L)

iCa2+

1.1-1.3mmol/L

Gambro PrismaGambro Prisma with withM60 AN69 FilterM60 AN69 Filter

QR

Prefilter Fluid: 4L bag

0.67% Trisodium Citrate Citrate3- 23 mM/L

Na+ 140 mEq/L

Rate: 1000-1500 mL/hr 24 mmol/h citrate

Gambro Prisma Pre-Pump Pre-Dilution Set

V

CRRT

Peritoneal Dialysis(PD)

• Salmon dialysis

• Peritoneal membrane

• Capillaries

• Diffusion, ultrafiltration( ie osmosis), convection, and absorption

PD Membrane

• Pd Membrane– surface area=BSA=1-2 m2

– heteroporus, heterogeneous semipermeable membrane with complex physiology

• Blood Flow– approx. 50-100 ml/min

• 3 pore model– large pores(macromolecules like proteins)– small pores(small solutes)– ultrapores(aquaporins)(water without solute)

PD Ultrafiltration

• Dextrose(3 concentrations) added to provide gradient for UF(osmosis)

• Glucose diffuses into blood and diminishes gradient

• Absorption of dialysate occurs limiting UF

• Newer agents

PD Clearance• High Transporters

– dialyze well– ultrafilter poorly

• ? Icodextran ?

– best with freq. short dwells

• High Avg/Low AVG transporters

• Low Transporters– ultrafilter well– dialyze poorly– best with longer short dwells

• Options– CAPD– CCPD

Future

• Which separation techniques improve mortality

• Less expensive RRT as population grows

• Improve patients quality of life

• Biological systems