Peritoneal Dialysis and Secondary 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

Methods

Animal model of uremia: Bilateral nephrectomies 45-60 kg female sheep performed in two surgical stages.Stage 1Left nephrectomy + PD catheters placement (infusion and removal)

Stage 2Right 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

BREC-d

F-80

F-40

MC3 pump Waste PD

Trilogy OUT

Trilogy IN

Roller pump

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)

Study Groups

Sheep Number BREC-d Cell type Duration of Study

3 Lamb 10 days

5 Lamb 10 days

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)

Normal Range for sheep (60-120 BPM)

Normal Range for Sheep (73-120 mmHg)

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20

40

60

80

100

120

140

Average Mean Arterial Blood Pressure: Acellular vs Cellu-lar

Error bars = SEMAcellular-BREC (n=5) Cellular-BREC (n=11)

Experimental Time (Hrs)

mm

Hg

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5

10

15

20

25

30

35

Average Sheep Central Venous Pressure per Treatment Group

Error bars = SEMAcellular-BREC (n=5) Cellular- BREC (n=11)

Experimental Time (Hrs)

mm

Hg

Normal Range for sheep (10-20 Breaths/Min)

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5

10

15

20

25

30

35

40

45

50

55

Average Sheep Respiration Rate per Treatment GroupError bars = SEM

Acellular-BREC (n=5) Cellular-BREC (n=11)

Experimental Time (Hrs)

Bre

ath

s/m

in

Reference Range 3.5-4.5mEq/L

0 1 2 3 4 5 6 7 80

1

2

3

4

5

6

7

8

Avg Acellular K+ Values (n=3)

Avg K+ Before PD Exchange Avg K+ After PD Exchange

Study DayPD Fluid Exchange Rate: 1/Day

mE

q/L

Reference Range 3.5-4.5mEq/LAvg Cellular K+ Values (n=3)

0

1

2

3

4

5

6

7

1 2 3 4 5 6 7 8 9 10

Study DaysPD Fluid Exchange Rate: 1/Day

mE

q/L

Avg K+before PD Exchange Avg K+ after PD Exchange

Metabolic Waste

BUN (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 impairment

Creatine- Another waste product produce through metabolism with an average range of 0.6-1.5 mg/dL

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40

60

80

100

120

140

Average PD Flow per Treatment GroupError bars = SEM

Acellular-BREC (n=5) Cellular-BREC (n=11)

Experimental Time (Hrs)

mL

/min

Pre Surgery

1

Pre Brecs Day 0

Brecs Day 1

Brecs Day 2

Brecs Day 3

Final0

10

20

30

40

50

60

70

80

90 Sheep 18 Metabolic Waste

BUN mg/dL (Reference Range 5.-20.)

Creatine mg/dL (Reference Range 0.6-1.5)

mg/dl

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 vivo

Average oxygen consumption in vitro is 19.24 mmoles of Oxygen/ min

This data illustrates that renal cells can survive in BREC-d environment.

Animal Oxygen Consumption of Recovered Renal Cells

Sheep 16 49.76 +/- 3.25 mmoles of Oxygen/ min

Sheep 17 35.88+/- 7.86 mmoles of Oxygen/ min

Sheep 18 33.08 +/- 4.18 mmoles of Oxygen/ min

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 exchangeTwice a day (am/pm)