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NON-TRADITIONAL RENAL REPLACEMENT THERAPY Hafez Bazaraa Slide 2 NON-TRADITIONAL RENAL REPLACEMENT THERAPY What? Why? How? Slide 3 RENAL FUNCTIONS Excretion of non-volatile wastes Water, electrolyte, acid-base balance Hormonal regulatory functions (EPO, Vit D,..) Slide 4 RENAL FAILURE Excretion of non-volatile wastes Water, electrolyte, acid-base balance Hormonal regulatory functions (EPO, Vit D,..) Slide 5 RENAL FAILURE RRT TRANSPLANTATIONDIALYSIS Slide 6 RENAL FAILURE RRT TRANSPLANTATIONDIALYSIS HDPD Deceased donor Living donor (Rel., Unrel.) Slide 7 RRT facts The kidney was the first solid organ whose function was approximated by a synthetic device. RRT with hemodialysis or CPD has been the only successful long term ex vivo organ substitution therapy to date. The kidney was the first organ to be successfully transplanted. Slide 8 Dialysis? Kolff, a Dutch physician constructed the first working dialyzer in 1943 during the Nazi occupation of the Netherlands Using sausage casings, beverage cans, a washing machine, and other items 16 patients with ARF unsuccessfully treated In 1945, a 67-year-old comatose woman regained consciousness following 11 hours of HD and lived 7 yrs before dying from an unrelated condition. Slide 9 Transplantation? 1906from sheep, pigs, goats and primates without anti-rejection drugs. 1936First human-to-human kidney transplant from a deceased donor with a different blood type. 1954First successful kidney transplant (identical twins) 1966 First successful pediatric kidney transplantation Slide 10 How traditional? Transplantation Modern VA Biocompatible dialyzer membranes Bicarbonate dialysis UF & Na profiling EPO, Active vit D CPD, CCPD Historical innovations NOW TRADITIONAL Slide 11 RRT: how traditional is non-traditional? Slide 12 Historical innovations Established non-traditional RRT Experimental/ future RRT & challenges Slide 13 NON-TRADITIONAL RENAL REPLACEMENT THERAPY What? Why? How? Partial RRT Survival vs quality of survival Risks of treatment Organ shortage Slide 14 NON-TRADITIONAL RENAL REPLACEMENT THERAPY What? Why? How? Partial RRT -Dx replaces mostly filtration -Not all functions -Intermittent nature Survival vs quality of survival - Inadequate long-term outcomes -Dependency -Quality of life Risks of treatment - Infections -Medication SE -VA complications -Pain, discomfort Organ shortage If you (logically) think Tx is the best option Slide 15 NON-TRADITIONAL RENAL REPLACEMENT THERAPY What? Why? How? Partial RRT Survival vs quality of survival Risks of treatment Organ shortage Slide 16 NON-TRADITIONAL RENAL REPLACEMENT THERAPY Transplantation modifications Dialysis modifications Intestinal dialysis Regenerative medicine The two-step dialysis concept Hybrids Whole-organ engineering WARNING Strange Ideas Ahead Slide 17 Transplantation practice Novel immunosuppression protocols Working with the immune system Cell therapies (MSCs, Treg, etc) Slide 18 Creatinine 113 D Urea 60 D Glucose 180 D Vit. B 12 1,355 D 2-M 11,800 D Albumin 66,000 D IgG 150,000 D Dialysis Membrane Flux and Selectivity Slide 19 CRRT Physiological (slow, continuous) Physiological (filtration-replacement) Well controlled therapy Complex, expensive therapy Slide 20 Back to nature 100 L/m2/d Plasma - proteins Slide 21 Ultrafiltration Replacement (substitution) Net UF (fluid removal) HEMOFILTRATION Slide 22 Solute transport: diffusion Slide 23 Solute removal: convection (solvent drag) Slide 24 Clearance: Convection vs. Diffusion Slide 25 Hemofiltration membrane permeability phosphate bicarbonate ionized Ca++ interleukin-6 endotoxin vancomycin heparin pesticides ammonia albumin protein-bound medications platelets Water Electrolytes Non-protein-bound Drugs Toxins Cytokines Slide 26 Long-term oHDF Slide 27 HD machine prepares substitute from ultrapure dialyzate (part of the benefit) Slide 28 Long-term oHDF B2 microglobulin amyloidosis EPO resistance MBD & hyperPTH Chronic infl. state CV outcome Slide 29 Daily nocturnal HD Again more physiological Fluid management advantages VA complications/loss ++ Dependency ++ Slide 30 Slide 31 home dialysis Home dialysis Slide 32 (trans) portable HD systems Home dialysis Slide 33 30-Kg dialysis machine PureFlow SL System: Compact water ttt + conc bags Nx Stage System One 2005 Systems using sorbents to regenerate dialysate (Fresenius; pending FDA approval) Slide 34 Intestinal dialysis imp Slide 35 Intestinal dialysis ESRD; GFR