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Fluid Management in Peritoneal Dialysis
Ali K. Abu-Alfa, MD, FASN Associate Professor of Medicine Director, Peritoneal Dialysis Program Associate Director for outpatient Dialysis Director of Clinical Trials Yale School of Medicine New Haven, Connecticut http://kidney.yale.edu

Educational Objectives

Review physiology of ultrafiltration and impact of membrane transport characteristics. Discuss fluid balance in PD with focus on clinical needs, goals and effect on outcomes. Identify areas of interventions for optimization of fluid removal. Identify patients at risk for fluid retention. Review role of alternative osmotic agents: Icodextrin. Review ISPD guidelines and clinical algorithms for fluid management in PD.

Physiology of Ultrafiltration

Trans-capillary fluid movement:
Osmotic gradient (first and foremost). Hydrostatic pressure (much less so). Membrane function / surface area.

Lymphatic re-absorption.

Physiology of Ultrafiltration: Structure of the Peritoneal Membrane

Physiology of Ultrafiltration: Water, Glucose and Sodium Movements Na

H2O

Capillary

Peritoneal Space Glucose
Aquaporin mediated: 50% Intercellular: 50% Glucose transporter mediated: minimal Intercellular: >90%

Physiology of Ultrafiltration: Sodium Sieving with 3.86% Dextrose Dialysate

LaMilia et al, Nephrol Dial Transplant (2004) 19: 1849-1855

Physiology of Ultrafiltration: Effect of Sodium Sieving on Na Removal

250 200 150 100 50 0 Na removal CAPD APD Icodextrin

Rodriguez-Carmona, PDI 2003 (22): 705-713.

Physiology of Ultrafiltration: Crystalloid versus colloid osmosis

Blood in Peritoneal Capillaries urea creatinine
Endothelium

macromolecules

glucose
Mesothelium

crystalloid colloid osmosis osmosis

Dialysate filled Peritoneal Cavity

LaMilia et al, Nephrol Dial Transplant (2004) 19: 1849-1855

Physiology of Ultrafiltration: Crystalloid Osmosis

Normal serum osmolarity = 270 mOsm/L1
Dextrose Dialysate
1.36% 2.27% 3.86%

mOsm/L
345 395 484

Daugirdas et al: Handbook of Dialysis, Third Edition, p 299, 2000

Physiology of Ultrafiltration: Net Ultrafiltration

Absorption 800 Cumulative transport (mL) 600 400 200 0 -200 -400 -600 -30 0 30

Transcapillary UF

Net UF

60

90

120

150

180

210

240

Time (min)

Mactier RA, et al. J Clin Invest. 1987;80:1311-1316.

UF: Ultrafiltration

Physiology of Ultrafiltration: Glucose Kinetics by Transport Status
1 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0 1 2 3 4
L: Low Transporter LA: Low Average Transporter HA: High Average Transporter H: High Transporter

D/D0 Glucose

L LA HA H

Hours
D/P: Dialysate / Plasma

Physiology of Ultrafiltration: Glucose Kinetics by Transport Status

16 14 12 10 8 6 4 2 0 -2 -4 0

Transcapillary UF

Osmolarity

500 450 400 350 300 250 200 Osmolarity (mosm/kg H2O)

Transcapillary UF (mL/min)

2

4 8 Dwell time (hr)

12

Data on file, courtesy of Baxter Healthcare Corporation.

Physiology of Ultrafiltration: Net Ultrafiltration: 1.36% Dextrose Dialysate
Low
400 200

Low-Avg

High-Avg

High

Net UF (ml)

0 -200 -400 -600 -800 0 2 4 6 8 10 12 14 16

Negative UF CAPD Overnight

APD Daytime

Hours
Mujais S, Vonesh E. Kidney Int. 2002;62(suppl 81):S17-S22.

Ti e h r m( )

Physiology of Ultrafiltration: Net Ultrafiltration: 2.26% Dextrose Dialysate

Low
800 600

Low-Avg

High-Avg

High

Net UF (mL)

400 200 0 -200 -400 -600 0 2 4 6 8 10 12 14 16
CAPD Overnight APD Daytime Negative UF

Time (hr)
Mujais S, Vonesh E. Kidney Int. 2002;62(suppl 81):S17-S22.

Physiology of Ultrafiltration: Net Ultrafiltration: 3.86% Dextrose Dialysate

Low
1800 1400

Low-Avg

High-Avg

High

Net UF (mL)

1000 600 200 -200 -600 0 2 4 6 8 10 12 14 16
CAPD Overnight

APD Daytime

Time (hr)
Mujais S, Vonesh E. Kidney Int. 2002;62(suppl 81):S17-S22.

Physiology of Ultrafiltration: Glucose absorption: Caloric Cost Widening differential
90 Glucose absorbed (g/8 hrs) 80 70 60 50 40 30 20 10 0 Low Low Ave. High Ave. High Peritoneal Transport Type 1.36% 2.27% 3.86%

Moberly J, Mujais S, et al. Kidney Int. suppl 81, Oct 2002

Physiology of Ultrafiltration: Changes in Transport Profile

70000 60000 50000 40000 30000 Year 1 Year 2 Year 3 Year 4 Year 5

Group 1 Group 2

0.8 0.75 0.7 0.65 0.6 0.55 0.5 Start Year 1 Year 2 Year 3 Year 4 Year 5

Group 1 Group 2

Davies et al. J Am Soc Nephrol. 2001;12:1046-51

Role of Fluid Management in PD

Maintaining adequate fluid balance is an important function of renal replacement therapy. Achieving optimal fluid balance is a component of PD adequacy. Optimal fluid management plays a key role in patient outcomes.

Importance of Fluid Management

Reduction in Symptomatic Fluid Retention. Blood pressure control: • Preservation of Residual Renal Function. • Prevention or mitigation of Cardiovascular Disease (IHD, LVH, CHF, CVA, PVD). • Reducing accelerated atherosclerosis process. • Prevention of symptoms simulating uremia. • Reduction in mortality.

Symptomatic Fluid Retention (SFR)

Symptomatic Fluid Retention

71 Episodes of SFR were identified in 66 PD patients. High rates of non-compliance with dietary salt and fluid restrictions as well as PD prescription were noted in the SFR group when compared to a control group (149 pts). Edema (100%), pulmonary congestion (80%) and hypertension (83%) were the most common manifestations of SFR.

Tzamaloukas et al, JASN (6): 198-206, 1995.

Prevalence of Hypertension in PD patients

40 35 % of Patients 30 25 20 15 10 5 0 Normal HighNormal Stage 1 Stage 2 Stage 3

Italy USA

JNC6 BP Category
Frankenfield DL, et al. Kidney Int. 1999;55:1998-2010. Cocchi R, et al. Nephrol Dial Transplant 1999;14:1536-1540.

Fluid Removal and Sodium Restriction: Impact on Blood Pressure control

47 hypertensive CAPD patients
Na Restriction (1.6 g/day for 4 weeks)

20 normotensive 27 hypertensive
Na Restriction and ↑ UF (3.86% use)

3 normotensive with enalapril 4 normotensive with enalapril

17 normotensive

7 hypertensive 3 hypertensive

Gunal et al, AJKD (37): 588-193, 2001

Fluid Removal: An Independent Predictor of Survival

Parameter RRF ( ↑ 1 ml/min/1.73 m2) Total Sodium Removal ( ↑ 10 mmol/24 hr/1.73 m2) Hypertension (present) Total Fluid Removal ( ↑ 100 ml/24 hr/1.73 m2)

Mortality RR 0.53 0.90 5.61 0.90

P-value

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