Peritoneal Dialysis andSecondary Renal Function
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
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.
Data Collection Hemodynamics: Heart Rate Mean Arterial Pressure Central Venous Pressure Respiratory Rate Electrolytes : K+ Renal function: BUN / CREAT PD Fluid Flow Rate
Roller BREC-d F-40 pumpF-80 Trilogy OUT MC3 Trilogy pump Waste PD IN
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)
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
Acellular Control Group (n=5) Vs.Cellular Study Group (n=11)
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
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)
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)
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.
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.
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.
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)