Principles of Hemodialysis (Part 1) PDF

Gilad Segev DVM, Dip. ECVIM-CA Hemodialysis Academy 2024  Renal replacement therapy relates to any form of artificial blood purification Extracorporeal Intracorporeal Mostly aimed to restore homeostasis in patients with acute kidney injury Removal of nitrogen w...

Gilad Segev DVM, Dip. ECVIM-CA Hemodialysis Academy 2024  Renal replacement therapy relates to any form of artificial blood purification Extracorporeal Intracorporeal Mostly aimed to restore homeostasis in patients with acute kidney injury Removal of nitrogen waste products, correction of acid base, electrolytes, and fluid imbalances Includes the prescription and delivery of the treatment at an adequate schedule 2  From the To the Blood is continuously aspirated from the dialyzer dialyzer patient using a double lumen catheter Blood is processed in artificial kidney where its composition is altered Blood is pumped back to the patient Treatment time IHD treatment is 4-5 hours CRRT treatment is >24 hours Expand the window of opportunity for recovery unlimited period of time in the absence of complications or financial constraints Associated with a better outcome  Intermittent Continuous renal Peritoneal hemodialysis replacement therapy dialysis 5 Intermittent hemodialysis Highly effective Frequency – trice weekly Continuous RRT Less effective Patients are continuously treated Peritoneal dialysis Even less effective Solute removal is achieved by inserting and draining dialysate fluids into and from the peritoneal space after a prescribed dwell time  Intermittent Continuous renal Peritoneal hemodialysis replacement therapy dialysis 7  Peritoneal CRRT Intermittent Dialysis hemodialysis Efficacy + +++ +++++ Training + ++ +++ Maintenance Very easy Relatively easy Relatively intense Cost + +++ +++++ Long Term - -/+ +++ As a single modality intermittent hemodialysis provides the highest flexibility 9 Artificial kidney - Dialyzer urea=172 mg/dl Blood Dialysate Urea=6 mg/dl  Principles of Hemodialysis HCO3- Blood Glucose HCO3- Ca++ Glucose Ca++ Na+ Na+ Creatinine PO4- K+ Urea Dialysate Principles of Solute Removal 12 https://www.youtube.com/watch?v=QmgMTXlc_r8  The hemodialysis apparatus is divided into the blood circuit and the dialysate circuit Both meet at the dialyzer 13  Blood circuit begins at the vascular access Blood is aspirated into the arterial line → dialyzer → back to the patient through the venous line  Despite this terminology only venous blood is being processed Various chambers and side ports attached to the circuit for blood access and monitoring 14  Dialysate solution is pumped through different compartments into the dialyzer After the dialysate was exposed to the blood (through the semipermeable membrane), dialysate solution is eliminated as a waste (single pass) Various monitors assure that the dialysate solution is at the correct temperature, pH and desired solute concentration 15  The dialysate in IHD is generated from purified water and concentrates: Acid concentrate Bicarbonate In CRRT dialysate is provided in sterile bags Dialysate composition will determine the blood composition at the end of the treatment During a single IHD treatment the patient is exposed to 120- 200 litters of dialysate (32-53 gallons) 16  Water are exposed to Particulate filters Carbon sorbents for organic solutes Water softeners to reduce excessive minerals Deionization beds to remove inorganic cations and anions Reverse osmosis is an essential treatment to remove residual contaminants 17  In some water purification systems ultraviolate light is used to kill microorganisms May increase LPS concentrations Ultrapure dialysate is generated within the dialysis machines Decreases chronic inflammation Enables hemodilafiltration 18  Dialysate final solute concentration is determined by the type of acid concentrate and the prescription Na and bicarbonate – direct programming of dialysis machine Concentration of other solutes  Determined by using different types of acid concentrate or by adding solutes to the acid component (phos, ethanol) 19 20  Blood in The dialyzer is the place where the Dialysate out blood and dialysate meet The blood from the patient flows into the dialyzer through the header Distributed through thousands of capillaries (hollow fibers) tightly bound to a bundle Dialysate in Dialysate flows around the fibers Blood out 22  Old dialyzers were made of cellulosic membranes Complement-activating due to the presence of numerous hydroxyl groups (OH-) Modern dialyzers are made of synthetic polymers lack hydroxyl groups Polysulfone Polyamide Dialysis in an inflammatory process Polyacrylonitrile Currently used dialyzers are very safe 23 Diffusion Ultrafiltration Convection Better targets middle-sized molecules Adsorption Dialysate  Solute exchange and removal occurs by Diffusion Convection Adsorption (minimal) Solute exchange dependents on Physical characteristics of the solute Ultrastructure of the porous membrane Which one of these principles is utilized by the native kidney? 25 Diffusion https://www.youtube.com/watch?v=tHzkRtzVmUM 26  Diffusion a consequence of random molecular movements (molecular kinetics) that follows the laws of probability Diffusion is driven by  Molecular size of the solute  Temperature  Pressure  Concentration gradient Temperature and pressure are relatively constant during dialysis → solute size and concentration difference is the major determinants of diffusion rate 27  Diffusion is derived by thermal motion of molecules in the solution The velocity of a molecule in solution is inversely proportional to its molecular weight Low molecular weight More encounters with the membrane More likely to fit in size pores Net diffusion occurs from high to low concentration until equilibrium 28  At equilibrium bidirectional exchange of solute occurs but there is no net diffusion 29  There is a linear relationship between diffusion rate and the concentration difference J = - (DA/X) ΔC J - solute flux (mg/min) ΔC - concentration gradient A - membrane area (cm2) X - membrane thickness – distance (cm) D - constant (cm2/min) 30  J = - (DA/X) ΔC Membrane thickness is relatively constant, rendering the concentration gradient and the surface area the major forces that determine flux This equation can be rewritten as J = - KoA ΔC 31  Ko is the mass transfer coefficient → membrane permeability for a specific solute (mL/min) Ko =J = Unit flux A Driving force -ΔC KoA A product of the mass transfer coefficient (KO), and the membrane area (A) Mass transfer area coefficient 32  Describes the maximum clearance of a solute across the dialyzer when blood flow (Qb) and dialysate flow (Qd) rates are infinite The KoA is constant for a given dialyzer Property of the solute and the dialyzer, including the membrane's pore size and thickness Can be calculated from basic transport values, if blood and dialysate flow rates are known Extraction ratio X 33  KoA is used to compare the performance of different dialyzers When known, the KoA can be used to calculate the clearance at any blood and dialysate flow rate X Proportional to the deriving force and is inversely proportional to a certain resistance The flux per area can be increased only by increasing the driving force, or decreasing the resistance (altering membrane characteristics) 34  A solute will have to overcome the resistance to flow within the blood, the membrane, and the dialysate The overall resistance (Ro) is determined by RB – blood resistance RM – membrane resistance RD – dialysate side resistance 36  ΔXB ΔXM ΔXD RB = RM = RD = DB kDM DD K – solute distribution coefficient between the membrane and the solution  For any particular solute the diffusivity in the blood and dialysate are constant A constant of the solution at a given temperature Should have the same value regardless of the dialyzer ΔXB ΔXM ΔXD RB = RM = RD = DB kDM DD 38  The effective resistances of a specific dialyzer will be governed by ΔXB ΔXB RB = DB ΔXD ΔXD ΔXM RD = DD The resistance of the membrane depends on the distance (membrane thickness - ΔXM) and the diffusivity of the membrane (DM) Vary by the chemical composition of the membrane 39 Efficiency of dialyzers have been improved by recognizing and reducing the value of the largest resistance  High efficiency dialyzers have a high urea KoA (>600-700 mls/min) To be advantageous, high efficiency dialyzers (high KoA) have large surface area, and high blood and dialysate flow should be prescribed At low blood flow rates ( dialysate side pressure 57  Determinants of ultrafiltration rate The transmembrane hydrostatic pressure (TMP) – pressure difference between the blood and dialysate compartments The hydraulic permeability The surface area of the membrane Blood Dialysate 58  Determined by physical features of the membrane Composition, thickness, pore size Relates to the ultrafiltration coefficient - Kuf TMP μ - solvent viscosity J= Rt - total resistance µRt Kuf –amount of fluid (mls) transferred per hour for each 1 mmHg of transmembrane pressure (TMP) Units = mls / hr / 1 mmHg 59  What is the required TMP to remove 600 mls/hr from a patient using a dialyzer with a KUF of 2 ? Ultrafiltration rate (mls/hr) = Kuf X TMP TMP = ultrafiltration rate / KUF TMP = 600 (ml/h) / 2 (mls/h/mmHg) = 300 mmHg 60  The Kuf is influenced by Hct and total protein concentration (oncotic pressure) A minimum of 25 mmHg of TMP is required to offset oncotic pressure of plasma proteins Ultrafiltration rate might change during treatment Blood clotting - surface area Changes in Hct 61  Negative trans-membrane pressure is undesirable as it will promote fluid shift from the dialysate side to the blood side → backflow Some hemodialysis machines will “require” a minimum amount of ultrafiltration to prevent backflow 62  In older dialysis machines, UF was achieved by manipulating the TMP (pressure control) Small errors in TMP measurement might have resulted in high volume change Less accurate Modern machines use volumetric control UF is determined by an ultrafiltration pump Dialysate inflow and outflow volumes are measured directly and continuously and the amount of UF is determined from the difference 63  Dialyzers are classified as low-flux or high-flux according to their Kuf High flux dialyzers have higher Kuf values Should be used only with machines equipped with special pumps that controls UF rate Important in small patients 64  A 30 kg dog presents for routine IHD treatment The dog is assessed to be 7% overhydrated The selected dialyzer has a Kuf of 15 mls/hr/mmHg Treatment time is 5 hours Can the dialyzer remove this amount of fluids ? 65  Amount of fluids to be removed 30 X 0.07 = 2.1 Dialysis treatment = 5 hours Amount of fluids to be removed/hr 2100 mls / 5 hrs = 420 ml/hr TMP = ultrafiltration rate / KUF TMP = 420 (ml/hr) / 15 (ml/hr/mmHg) TMP = 28 mmHg 66  In veterinary medicine the Kuf rarely limits the rate of fluid removal Use of high flux dialyzers Rate of fluid removal is typically limited by the patient 67  Roxy, a 8 year old MC, 20 kg mixed breed dog is presented for a routine dialysis treatment (5 hours) Assessed to be 8% overhydrated Questions: Can the dialyzer remove this amount of fluids over 5 hours ? Can Roxy tolerate this rate of fluid removal ? 68  Roxy, a 8 year old MC, 20 kg mixed breed dog 0.08 X 20 = 1600 mls 1600 mls / 5 hours = 320 mls/hr 320 mls/hr / 20 kg = 16 mls/kg/hr 69 IV ECF ICF  Rate of fluid removal depends on Degree of overhydration Rate of fluid shift between body compartments Individual for each patient ~10 mls/kg/hr Assessed continuously during the treatment Clinical assessment Blood volume and saturation monitor Blood pressure 71 72  Critline monitor Venous saturation  Marker of tissue perfusion Changes in Hct /changes in blood volume 73  Variables associated with UF complications Initial (within 15-30 min) blood volume change Initial venous oxygen saturation Nadir venous oxygen saturation Temperature prior to treatment initiations Total extracorporeal circuit volume 74 75 Convection 76  Convection → removal of solutes by solvent drag Occurs with ultrafiltration Less influenced by molecular size Solutes exchange is independent of  Random molecular movement  Concentration gradient Solute transfer does not alter diffusive gradients  Solutes and water move together Solute removal does not alter the solute blood concentration 77  Convection can be utilized to promote clearance of large molecular size molecules Middle size uremic solutes Cytokines Lactate Sieving coefficient (S): ratio of solute filtrate concentration (Cf) to the respective solute plasma concentration (Cp): Convective clearance: : 78  What is the relative convective clearance compared with the overall clearance in IHD A 9 year old MC, mixed breed dog presents for a routine IHD treatment The dog is assessed to be 7% overhydrated Prescription: Blood flow rate (Qb) – 200 mls/min  H-120 dialyzer (measured extraction ratio at 200 mls/min - 75%) Dialysate flow rate (Qd) – 500 mls/min Treatment time – 300 min Ultrafiltration rate – 200 mls/hr 79  What is the relative contribution of the convective clearance (compared to the diffussive clearance) 200 mls/min X 0.75 = 150 mls/min 150 ml/min X 300 min = 45000 mls Convective clearance - 200 mls/hr  200 mls/hr x 5 hrs = 1000 mls Relative contribution 1000/45000 = 0.02 (2%) Blood flow rate (Qb) – 200 mls/min Dialysate flow rate (Qd) – 500 mls/min ER at 200 mls/min - 75% Treatment time – 300 min Ultrafiltration rate– 200 mls/hr 80  High molecular weight solutes are implicated in the development of variety of clinical signs in chronic hemodialysis patients Insomnia Pruritus Irritability Restless legs syndrome Anemia Osteoarticular pain Convective clearance enables the removal of solutes up to 40KD 81  How can we increase convective clearance ? Convective clearance can be maximized by increasing ultrafiltration and replacing the fluid with a pre- or post- filter solution Hemodiafiltration 82  Effect of molecular size and homofilters on removal rate using HDF 11.8 kDa 23 kDa 33 kDa Blood purification 2013 (sup 64-68) 83  Maximizing convective clearance by increasing ultrafiltration and replacing the fluids The cost of sterile solution limits this option HDF equipment allows online preparation of ultrapure and pyrogen-free replacement fluids, infused directly into the extracorporeal circuit, facilitating clearance of large molecular weight solutes https://www.youtube.com/watch?v=eQPBET2ZjkY 84  Meta analysis of 6 RCT Beneficial effect of online post-dilution HDF over HD in reducing all-cause and cardiovascular mortality A dose response relationship between the convective volume and outcome 85 86  Diffusion Conventional intermittent hemodialysis J = - (DA/X) ΔC Peritoneal dialysis CRRT - continuous venovenous hemodialysis  CVVHD Convection CRRT - continuous venovenous hemofiltration  CVVH Hemodiafiltration Some intermitted hemodialysis machines CRRT - continuous venovenous hemodiafiltration  CVVHDF 87  Which of the following principles is “utilized” by the native kidney to remove uremic toxins? Diffusion Convection 88  Kuf – mls of fluid transferred per hour for each 1 mm Hg of transmembrane pressure (TMP) TMP J= µRt With the use of high flux dialyzers, UF rate is limited by the patient and not the dialyzer Units = mls / hr / 1 mmHg 89  Modern hemodialyzers have a very large surface area compared to their priming volume Enable effective solute removal with a relatively low extracorporeal blood volume  Important in veterinary patients High efficiency and high flux  High efficiency – very effective removal of low (< 500 D) low MW solutes. Less effective removal of middle size MW (500 – 15000 D) solutes  High flux – high Kuf Regulate water and solute removal independently Due to the use of high efficiency dialyzers (large pores) the blood might be exposed to contaminants (e.g., pyrogens) 92  Describes the maximum clearance of a solute across the dialyzer when blood flow (Qb) and dialysate flow (Qd) rates are infinite The KoA is constant for a given dialyzer Property of the solute and the dialyzer, including the membrane's pore size and thickness Used to compare dialyzers’ performance and to calculate clearance at any blood and dialysate flow rate 93  Can be calculated directly for each solute by measuring the concentration in the inlet and the outlet of the dialyzer Extraction ratio Is that a clearance of urea ? 94  Clearance is defined as the plasma volume that is completely cleared from a solute The clearance rate for urea is calculated as follows: 95  Comparing of different dialyzers 96  250 200 Clearance (mls/min) 150 100 50 0 0 50 100 150 200 250 300 Blood flow (ml/min) 97  250 200 Clearance (mls/min) 150 100 50 0 0 50 100 150 200 250 300 Effluent dose (ml/min) 98  250 Polyflux 170 200 Clearance (mls/min) 150 Polyflux 140 100 50 0 0 50 100 150 200 250 300 Blood flow (ml/min) 10 1 10 2