Fluid Management in PDDr Abdullah Alhwiesh

Associated Professor of Internal Medicine and Nephrology

Introduction

Ultrafiltration Process

Ultrafiltration Failure

Definition

Incidence

Approach

Types

Management

General

Specific

Peritoneal Membrane (PM) Lines the peritoneal cavity

PM surface area 1-2 m2

PM/Body SA 0.6-0.8

Two Portions

1. Visceral

a. Lines the gut and other viscera

b. 80-90% of total SA

c. 25-30% participate in PD

2. Parietal

a. Lines the abdominal cavity wall

b. 10-20% of total SA

c. 70-75% participate in PD

Transport Process Diffusion

High concentrated area to the low concentrated area

Ultrafiltatration (convection)

Osmotic gradient

Water move from low osmotic area to high area

Absorption

Lymphatic system

Barriers Between the Dialysate and

Capillary Blood

Three-Pore Capillary Membrane

Ultrafiltration (UF)

40% of UF by aquaporin system

60% of UF by paracellular route

UF depends on osmotic gradient

Maximum at the beginning of dwell but decline with time due to:

1. Glucose absorption

2. Dilution of the dialysate

Dia

lysate

glu

cose

(mg

/dL)

Dwell time (hours)

Dialysate Glucose Level

UF is counterbalanced by peritoneal reabsorption:

1. Lymphatic, varies directly with intraperitoneal

pressure

2. Backfiltration

Net fluid removal depends on the balance:

UF and absorption

Usually there is inverse relationship between UF

volume and solute clearance.

UF (cont.)

Net UF Volume

Peritoneal Equilibration Test (PET)

TransportClassification

D/PCreatinine

Dialysate Glucose (mg/dL)

Net UF (mL)

HighHigh Average

MeanLow Average

Low

0.82-1.030.66-0.81

0.650.50-0.640.34-0.49

230-501502-722

723724-944

945-1,214

-470-3535-320

320320-600

600-1,276

Baseline PET

10.4%

53%

30.9%

5.6%0

10

20

30

40

50

60

High High AverageLow Average Low

%

PD n=806

Blake, P, et al. PD I 1996;16:448-456

Transport Status Changes

Blake PG, et al. Adv Perit Dial 1989;5:3

8% convert to low transporter at two years

UF Volume and Solute Clearance

Twardowski ZJ, ASAIO Trans 90;36:8

The mean TCUF for 4 hours dwell:

1. 1.5% Dextrose (1.36% glucose) 346 mosmol/kg (MW 182 dalton)

1.0 – 1.2 mL/min (240 mL/4 hr)

2.5% dextrose (2.27% glucose) 396 mosmol/kg

1.7 mL/min (400mL/4hr)

3. 4.25% Dextrose (3.86% glucose) 484 mosmol/kg

3.4 ml/min (816 mL/4 hr)

7.5% icodextrin (glucose polymer) 282 mosmol/kg (MW 20,000 dalton)

UF maintained over at least 12 hours

UF 1.4-2.3 mL/min

UF (cont.)

UF VolumeU

ltra

filt

rati

on

(m

L)

Time (h)

1.5% dextrose

4.25 % dextrose

Icodextrin vs 1.5% and 4.25% Dextrose

RCT, MC CAPD FU 6 months

(MIDAS Study Group) Mistry CD, et al. KI 94:46;496-503

Ico1.5 % Dextrose4.25% Dextrose

0

100

200

300

400

500

600 527

150

510

448

561

101

552

414

n=46n=53 n=29 n=45 n=45 n=54 n=30 n=35

P<0.0001 P=0.44 P<0.0001 P=0.06Dwell time 8 hours 12 hours

Mean

Net

UF V

olu

me

(mL)

Icodextrin vs 4.25% DextroseN

et

UF M

L

540

195

0

100

200

300

400

500

600

Icodextrinn = 47

4.25 % Dextrosen = 45

RCT, DB, MC APD FU 2/52 dwell time 14 hrs mean D/P Cr 0.84

Finkelstein, F, et al JASN 2005;16:546-554

P<0.001

0

100

200

300

400

500

600 587.2

346.2

P< 0.001

Mea

n N

et U

F Vo

lum

e (m

L)

7.5 Icodextrin 2.5 % Dextrose

n=90 n=85

RCT, DB, MC CAPD FU 4/52 dwell time 10.5 h (Icodextrin Study Group) Wolfson M, et al. AJKD 2002;40:1055-65

Icodextrin vs 2.5% Dextrose

Theoretical Concern7.5% Icodextrin

20% absorbed

Maltose

Accumulate in the Body

No Toxic Effects

Met

abol

ized

Can

not b

e

M

etab

oliz

ed

Mistry CD, et al KI 94;46:496-503

Wolfson M, et al AJKD 2002; 40:1055-65

UltrafiltrationTFR > 2035 mL/24hTFR 1570-2035 mL/24h

TFR 1265-1570 mL/24hTFR < 1265 mL/24h

Each 100 mL/24h of TFR, RR 0.90 (95% CI, 0.84 to 0.96)P < 0.01

Prospective, observational study CAPD 93% n=125 FU 3 yearsMean UV 364 mL/24h UV 21.8%

Ates, et al. KI 2001;60:767-776

82%

56%

0

10

20

30

40

50

60

70

80

90 RR 0.45 P=0.047

UF mL/day >750 <750 n =131 n = 43

Pati

en

t S

urv

ival %

Prospective, observational, MC anuric APD median Ico 50% FU 2 yrs

(EAPOS) Brown, EA, et al. JASN 2003; 14: 2948-2957

Ultrafiltration

UF Failure Definition:

UF Volume < 400 mL after 4 hours dwell with 2L of 4.25% dextrose (3.86% glucose)

Fluid overload is risk factor for CV morbidity and mortality

UF failure is important cause of PD technique failure 1-6%

Incidence: 10-40%

Heimburger O, et al KI 90;38:495 - 506

2.6% after 1 year

30.9% after 6 years

Causes of Fluid Overload Fluid overload is not always due to UF failure

Causes of fluid overload:

A) Non-membrane related e.g.

excess salt and water intake

severe hyperglycemia

non-compliance with exchanges

inappropriate hypertonic solutions

loss of residual renal functions

mechanical causes I.e leaks, catheter obstruction or malposition

• A) Membrane related (UF Failure)» 3 types (1,2, and 3) based on modified

peritoneal equilibration test (PET) to evaluate UF response and small MW solute transport

Causes of Fluid Overload

UF FailurePeritoneal membrane function

Ultrafiltration Response

Modified PET 4.25 % 2L

Drain Volume < 2400 ml/4hrs

Drain Volume > 2400 ml/4hrs

Small Solute Profile Re-evaluate

clinically

UF FailureSmall Solute Profile

High Transport D/PCr > 0.81

Low Transport D/PCr < 0.5

HA or LA D/PCr 0.5-0.81

Disruption of Peritoneal Space

Inherent high/

Recent peritonitis/ Longterm PD

Mechanical/

Enhanced Reabsorption/

Aquaporin Deficiency

Type 2 Type 1 Type 3

Type 1 UF Failure Low UF volume (< 400 ml/4h with 4.25% dextrose

modified PET)

and high small MW solute transport status (D/P Cr > 0.81)

Most common

Three Groups:

1. Patient with inherent high transporter, 10% of starting PD

2. Patients with peritonitis

3. Patients who converted to high transporter with time.

Risk of high protein loss

Higher mortality

Pathophysiology of Type 1 UF Failure

Vascular permeability / Vascularity

Effective PM surface area

Rapid Dialysate Glucose Absorption

Loss of Osmotic Gradient

(Low UF Volume & High Small MW Solute Clearance)

Type 1 UF Failure

Peritoneal Neoangiogenesis

Constant Glucose Exposure

Type 2 UF Failure Low UF volume ( < 400 ml/4 h with 4.25% dextrose

modified PET) and low small MW solute transport status

(D/P Cr < 0.5)

Very rare

Causes:

1. Peritoneal fibrosis/sclerosis

2. Intraabdominal adhesions

3. Scleresing encapsulating peritonitis

Low transporter and leaks or mechanical problems or

high lymphatic reabsorption can mimic type 2 UF failure.

Pathophysiology of Type 2 UF FailureIrritants e.g peritonitis

Stimulate PM macropahages

Secreate lymphokines

PM fibrosis

PM permeability

Activate fibroblast

(Low UF Volume & Low Small MW Solute Clearance)

Type 2 UF Failure

Abdominal Operation/intra-abdominal inflammation

Extensive Adhesion Formation

Effective PM Surface Area

(Low UF Volume and Low Small MW Solute Clearance)

Type 2 UF Failure

Type 3 UF Failure

Low UF volume (< 400ml/4 h with 4.25% dextrose

modified PET) and low average or high average small

MW solute transport status (D/P Cr 0.5-0.81)

Causes:

1. lymphatic absorption

2. Aquaporins loss or dysfunction

Lymphatic Absorption Absorption process is independent of osmotic

pressure

Absorption process is dependent on intraperitoneal pressure

Net UF 16% higher in supine position

Imholz AL, et al. NDT 98;13:146

Absorption rate 1-1.5 ml/min

Associated with large PM surface area

Increased PD duration does not enhance lymphatic

absorption

Michels WM, et al. PDI 2004;24:347

Measurement of lymphatic absorption is uncommon in

clinical practice due to complexity of the procedure.

Pathophysiology of Aquaporins Dysfunction Type 3 UF Failure

Transcellular glycosylation of aquaporin-1

Impaired aquaporin-1 function

Type 3 UF Failure

Peritoneal Neoangiogenesis

Constant Glucose Exposure

(Low UF Volume & Low Average or High Average Small MW Solute Clearance)

Aquaporins Loss or Dysfunction

Rare Condition

Various indirect methods to estimate aquaporin function:

Sodium Sieving

Difference in net UF between 4.25 % and 1.5 % dextrose UF after 2-4h dwell with 4.25% dextrose UF

after 4h dwell

with 1.5% dextrose

Sodium Sieving

General Guidelines for Prevention of Volume Overload1. Routine Monitoring

Dry Weight, Residual Renal Function, blood pressure, PET

2. Dietary Counselling Appropriate salt and water intake

3. Protection of Residual Renal Function (RRF) Avoidance of nephrotoxic agents e.g. NSAIDs

aminoglycosides, contrast

4. Diuretics Use Urine Output Furosemide (500 mg x 3wk or 500 mg PO OD or 200 mg

PO BID) with or without metolazone (5-10 mg) 30 min prior to furosemide

Do not preserve RRF

Diuretics and RRF

Variable Controln=30

Diureticsn=31

P Value

Urine Vol. mL/month CrCl mL/min/month Urinary Kt/v per month

-23.3 11.2-0.071 0.04-0.019 0.01

+6.47 9.52-0.12 0.050.020 0.01

0.0470.450.92

RCT CAPD FU 1 year

Furosemide 250 mg PO OD Metolazone 5 mg PO OD

Medcalf JF, et al KI 2001;59:1128-33

5. Education to enhance compliance

6. Appropriate prescription

7. Hyperglycemia control

8. Preservation of PM function

Decrease the peritonitis rate

Use more bicompatible solutions

Reductions of PM glucose exposure

General Guidelines for Prevention of Volume Overload

What is the ideal solution ?

1 - Have a sustained and a predictable solute clearance with minimal absorption of the osmotic agents .

2 - Provide deficient electrolytes and nutrients, if required .

3 - Correct acid base problems without interacting with other solutes in the peritoneal dialysis fluid .

4 - Be free of and inhibit the growth of pyrogens and micro-organisms .

5 - Be free of toxic metals .

6 - Be inert to the peritoneum .

Low molecular weight agents : 1- Glucose (Dextrose)- The most commonly used - 3 different dextrose monohydrate concentrations 15%, 2.5% , and 4.25%-Advantages :- Cheap- Safe - Easily available In market for long time.

- -Not ideal osmotic agent : - ● easily absorbed so short UF ● Absorption→ Metabolic complications : Hyperglycemia Hyperinsulinemia Hyperlipidemia Obesity ● Hyperosmolarity , low PH , GDPs affect Peritoneal host defense

mechanisms by inhibiting :Phagocytosis and bactericidal activity (Bio- incompatibility )

High molecular weight agents :

Glucose polymers ( Icodextrin 7.5%)

- Mixtures of oligopolysacchaides of variable

chain lenghts .

- Substitute for glucose solutions :

- Diabetics .

- If long dwell is required .

- If Better UF is required .

Advantages :

- Prolonged positive UF because of slow

absorption ( large MW) .

- Iso-Osmolar : (282)

It induces transcapillary UF by a

mechanism resembling colloid

osmosis mainly through small pores .

Almost no sieving of solutes→ increased convective transport and clearance of small solutes .

Sustained UF Potential Icodextrin vs Dextrose

-800-600-400-200

0200400600800

10001200

0 2 4 6 8 10 12 14 16

Time (hrs)

Net

UF

(m

L) 1.5% dextrose

2.5% dextrose

4.25% dextrose

7.5% icodextrin

Ho-Dac-Pannekeet et al. Kidney Int 1996;50:979-86; Douma et al. Kidney Int 1998;53:1014-1021; Mujais S et al. Kidney Int 2002; 62(Suppl 81): S17-S22

2- Balance

Bi-chamber bags.

Neutral PH, low GDPS

Aretrospective study : over 2000 Pts

Conventional solutions vs Balance

Comparing the outcome and survival :

high with balance but it was a retrospective study therefore a randomized Prospective studies are required .

Lee Hy etal Perit Dial Int 2005 ; 25:248

3- Amino acid solutions :

- Malnutrition is common in PD patient : higher mortality higher hospitality

- Multi-factorial etiology ? Protein loss (15 grams/day)- Early Experience with AA solutions not very successful

? not well designed for PD - Nutrineal 1.1% solution of combination of essential and nonessential AA is as effective as 1.36% Dx solutions and improve the nutritional status of dialysis Pts. A/e : • worsening of acidosis • ↑BUN • Expensive

Management of Type 1 and 3 UF Failure

Use icodextrin in long dwell Avoid long dwell:

1. CAPD

a. Use automated night-time exchange device

b. Switch to APD ( lymphatic absorption)

2. APD

a. Dry daytime

b. Mid-day drainage

c. Dwell 3-4 hours before APD

d. One or more daytime exchanges Resting membrane temporary switch to HD (4/52)

23/33 (69%) respond (Type 1 UF failure) Switch to HD permanently

Garosi G, at al. Adv PD 1999;15:185

Management of Type 2 UF Failure

Use loop diuretics in patients with RRF

Majority, transfer to HD permanently