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Peritoneal Dialysis And Secondary Renal Function

Jack Kent Cooke research fellowship presentation.

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Peritoneal Dialysis And Secondary Renal Function

  1. 1. Peritoneal Dialysis andSecondary Renal Function
  2. 2. Background/Goals End Stage Renal Disease (ESRD) Current therapy: - Peritoneal Dialysis vs. Hemodialysis - Few kidneys available for transplantation Development of a viable renal function replacement system
  3. 3. MethodsAnimal model of uremia: Bilateral nephrectomies 45- 60 kg female sheep performed in two surgical stages. Stage 1 Left nephrectomy + PD catheters placement (infusion and removal) Stage 2 Right nephrectomy, lines placed in carotid artery and jugular vein (to monitor and control hemodynamics).PD and BREC-d was turned on 24 hrs after second surgery.Data was collected up to 10 days.
  4. 4. Data Collection Hemodynamics:  Heart Rate  Mean Arterial Pressure  Central Venous Pressure Respiratory Rate Electrolytes :  K+ Renal function:  BUN / CREAT PD Fluid Flow Rate
  5. 5. Roller BREC-d F-40 pumpF-80 Trilogy OUT MC3 Trilogy pump Waste PD IN
  6. 6. Study Groups Control (n=5)  Acellular BREC-d Study - Cellular (n=11): Renal Epithelial Cells  Lamb BREC-d (n=6)  Human BREC-d (n=5)
  7. 7. Sheep Number BREC-d Cell type Duration of StudyStudy 3 Lamb 10 days 5 Lamb 10 daysGroups 6 Lamb 10 days 7 Lamb 7 days 8 Lamb <1 day 9 Lamb 8 days 11 Human <1 day 12 Human 10 days 16 Human 10 days 17 Human 10 days 18 Human 10 days 20 Acellular 2.5 days 21 Acellular 5 days 22 Acellular 10 days 23 Acellular 7 days 24 Acellular 10 days
  8. 8. Acellular Control Group (n=5) Vs.Cellular Study Group (n=11)
  9. 9. Normal Range for sheep (60-120 BPM)
  10. 10. Normal Range for Sheep (73-120 mmHg) Average Mean Arterial Blood Pressure: Acellular vs Cellular Error bars = SEM Acellular-BREC (n=5) Cellular-BREC (n=11) 140 120 100mmHg 80 60 40 20 0 0 24 48 72 96 120 144 168 192 216 240 Experimental Time (Hrs)
  11. 11. Average Sheep Central Venous Pressure per Treatment Group Error bars = SEM Acellular-BREC (n=5) Cellular- BREC (n=11) 35 30 25mmHg 20 15 10 5 0 0 24 48 72 96 120 144 168 192 216 240 Experimental Time (Hrs)
  12. 12. Normal Range for sheep (10-20 Breaths/Min) Average Sheep Respiration Rate per Treatment Group Error bars = SEM Acellular-BREC (n=5) Cellular-BREC (n=11) 55 50 45 40Breaths/min 35 30 25 20 15 10 5 0 0 24 48 72 96 120 144 168 192 216 240 Experimental Time (Hrs)
  13. 13. Reference Range 3.5-4.5mEq/L Avg Acellular K+ Values (n=3) Avg K+ Before PD Exchange Avg K+ After PD Exchange 8 7 6 5mEq/L 4 3 2 1 0 0 1 2 3 4 5 6 7 8 Study Day PD Fluid Exchange Rate: 1/Day
  14. 14. Reference Range 3.5-4.5mEq/L Avg Cellular K+ Values (n=3) Avg K+before PD Exchange Avg K+ after PD Exchange 7 6 5mEq/L 4 3 2 1 0 1 2 3 4 5 6 7 8 9 10 Study Days PD Fluid Exchange Rate: 1/Day
  15. 15. Metabolic WasteBUN (Blood Urea Nitrogen)Natural bi-product of metabolic function, can cause damage to tissue if not excreted.Value greater than 60mg/dl indicates severe renal impairmentCreatine- Another waste product produce through metabolism with an average range of 0.6-1.5 mg/dL
  16. 16. Average PD Flow per Treatment Group Error bars = SEM Acellular-BREC (n=5) Cellular-BREC (n=11) 140 120 100mL/min 80 60 40 20 0 0 24 48 72 96 120 144 168 192 216 240 Experimental Time (Hrs)
  17. 17. Sheep 18 Metabolic Waste 90 80 70 60 50mg/dl 40 30 20 10 0 Pre Pre Brecs Brecs Day Brecs Day Brecs Day Final Surgery 1 Day 0 1 2 3 BUN mg/dL (Reference Range 5.-20.) Creatine mg/dL (Reference Range 0.6-1.5)
  18. 18. Comparative BUN and Creatine Data Due to constant recirculation of PD fluid, metabolic wastes such as blood urea nitrogen (BUN) and creatine reach elevated levels. Recirculation occurs so that renal cells can be kept alive Thus PD effectiveness is significantly reduced BREC-d does not replace primary functions, therefore no effect on metabolites.
  19. 19. Viability of Renal Cell System Oxygen Consumption in vivoAnimal Oxygen Consumption of Recovered Renal CellsSheep 16 49.76 +/- 3.25 mmoles of Oxygen/ minSheep 17 35.88+/- 7.86 mmoles of Oxygen/ minSheep 18 33.08 +/- 4.18 mmoles of Oxygen/ min Average oxygen consumption in vitro is 19.24 mmoles of Oxygen/ min This data illustrates that renal cells can survive in BREC-d environment.
  20. 20. Conclusions Cellular BREC-d maintains acceptable MAP. Respiration rate elevated  Discomfort due to dialysate volume More PD fluid exchanges necessary to better control K+; BUN; CREAT Renal cells are viable for course of study.
  21. 21. Future Research More effective PD fluid Analyze effects of BREC-d unit for longer period time (>2 weeks) Analyze sheep vs human BREC-d Increase frequency of PD fluid exchange Twice a day (am/pm)

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