1. Associated Professor of Internal Medicine and Nephrology
Fluid Management in PD
Dr Abdullah Alhwiesh
Associated Professor of Internal Medicine and Nephrology

2. Introduction
Ultrafiltration Process
Ultrafiltration Failure
Definition
Incidence
Approach
Types
Management
General
Specific

3. Peritoneal Membrane (PM)
Lines the peritoneal cavity
PM surface area 1-2 m2
PM/Body SA
Two Portions
1. Visceral
a. Lines the gut and other viscera
b % of total SA
c % participate in PD
2. Parietal
a. Lines the abdominal cavity wall
b % of total SA
c % participate in PD

4. Transport Process High concentrated area to the low concentrated area
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

5. Barriers Between the Dialysate and
Capillary Blood

6. Three-Pore Capillary Membrane

7. 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

8. Dialysate Glucose Level
Dialysate glucose (mg/dL)
Dwell time (hours)

9. UF (cont.) 1. Lymphatic, varies directly with intraperitoneal pressure
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.

10. Net UF Volume

11. Peritoneal Equilibration Test (PET) Dialysate Glucose (mg/dL)
Transport
Classification
D/P
Creatinine
Dialysate Glucose (mg/dL)
Net UF
(mL)
High
High Average
Mean
Low Average
Low
0.65
723
945-1,214
35-320
320
600-1,276

12. Baseline PET 60 53% 50 40 30.9% 30 20 10.4% 5.6% 10 High High Average
High
High Average
Low Average
Low
PD n=806
Blake, P, et al. PD I 1996;16:

13. Transport Status Changes
8% convert to low transporter at two years
Blake PG, et al. Adv Perit Dial 1989;5:3

14. UF Volume and Solute Clearance
Twardowski ZJ, ASAIO Trans 90;36:8

15. UF (cont.)
The mean TCUF for 4 hours dwell:
% 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)
% 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 mL/min

16. UF Volume
4.25 % dextrose
Ultrafiltration (mL)
1.5% dextrose
Time (h)

17. Icodextrin vs 1.5% and 4.25% Dextrose
100
200
300
400
500
600
527
150
510
448
561
101
552
414
Mean Net UF Volume (mL)
n=46n= n=29 n= n=45 n= n=30 n=35
P< P= P< P=0.06
Dwell time hours hours
RCT, MC CAPD FU 6 months
(MIDAS Study Group) Mistry CD, et al. KI 94:46;

18. Icodextrin vs 4.25% Dextrose
600
540
P<0.001
500
400
Net UF ML
300
195
200
100
Icodextrin
n = 47
4.25 % Dextrose
n = 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:

19. Icodextrin vs 2.5% Dextrose
600
587.2
500
P< 0.001
400
346.2
Mean Net UF Volume (mL)
300
200
100
7.5 Icodextrin % Dextrose
n= n=85
RCT, DB, MC CAPD FU 4/ dwell time 10.5 h
(Icodextrin Study Group) Wolfson M, et al. AJKD 2002;40:

20. Theoretical Concern 7.5% Icodextrin 20% absorbed Maltose
Metabolized
Maltose
Cannot be Metabolized
Accumulate in the Body
No Toxic Effects
Mistry CD, et al KI 94;46:
Wolfson M, et al AJKD ; 40:

21. Ultrafiltration
TFR > 2035 mL/24h
TFR mL/24h
TFR mL/24h
TFR < 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= FU 3 years
Mean UV 364 mL/24h UV 21.8%
Ates, et al KI 2001;60:

22. Ultrafiltration 90 82% RR 0.45 P=0.047 80 70 56% 60 50 40 30 20 10
Patient Survival % 40 30 20 10
UF mL/day > <750
n = n = 43
Prospective, observational, MC anuric APD median Ico 50% FU 2 yrs
(EAPOS) Brown, EA, et al JASN 2003; 14:

23. 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:
2.6% after 1 year
30.9% after 6 years

24. 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

25. Causes of Fluid Overload
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

26. UF Failure Peritoneal membrane function Ultrafiltration Response
Modified PET 4.25 % 2L
Drain Volume < 2400 ml/4hrs
Drain Volume > 2400 ml/4hrs
Re-evaluate
clinically
Small Solute Profile

27. UF Failure Type 2 Type 1 Type 3 Small Solute Profile
Low Transport D/PCr < 0.5
High Transport D/PCr > 0.81
HA or LA D/PCr
Inherent high/
Recent peritonitis/ Longterm PD
Mechanical/
Enhanced Reabsorption/
Aquaporin Deficiency
Disruption of Peritoneal Space
Type 2
Type 1
Type 3

28. 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

29. 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

30. 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.

31. Pathophysiology of Type 2 UF Failure
Irritants e.g peritonitis
Abdominal Operation/intra-abdominal inflammation
Stimulate PM macropahages
Extensive Adhesion Formation
Secreate lymphokines
Activate fibroblast
 Effective PM Surface Area
PM fibrosis
 PM permeability
Type 2 UF Failure
Type 2 UF Failure
(Low UF Volume and Low Small MW Solute Clearance)
(Low UF Volume & Low Small MW Solute Clearance)

32. Type 3 UF Failure modified PET) and low average or high average small
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 )
Causes:
1.  lymphatic absorption
2. Aquaporins loss or dysfunction

33. 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 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.

34. Pathophysiology of Aquaporins Dysfunction Type 3 UF Failure
Constant Glucose Exposure
Peritoneal Neoangiogenesis
Transcellular glycosylation of aquaporin-1
Impaired aquaporin-1 function
Type 3 UF Failure
(Low UF Volume & Low Average or High Average Small MW Solute Clearance)

35. 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

36. Sodium Sieving

37. General Guidelines for Prevention of Volume Overload
1. 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

38. Diuretics and RRF Variable Control n=30 Diuretics n=31 P Value
 Urine Vol. mL/month
CrCl mL/min/month
Urinary Kt/v per month
-23.3  11.2
 0.04
 0.01
+6.47  9.52
-0.12 0.05
0.020 0.01
0.047
0.45
0.92
RCT CAPD FU 1 year
Furosemide 250 mg PO OD  Metolazone 5 mg PO OD
Medcalf JF, et al KI ;59:

39. General Guidelines for Prevention of Volume Overload
Education to enhance compliance
Appropriate prescription
Hyperglycemia control
Preservation of PM function
Decrease the peritonitis rate
Use more bicompatible solutions
Reductions of PM glucose exposure

40. What is the ideal solution ?

41. 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 .

42. 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 )

43. 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 .

44. 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 .

45. Sustained UF Potential Icodextrin vs Dextrose
As shown on this slide, computer modeling using actual peritoneal transport data from patients with high-average transport profile on continuous ambulatory peritoneal dialysis1-3 confirms simulated ultrafiltration (UF) profiles across a variety of peritoneal dialysis (PD) solutions.4
As predicted, dextrose-based PD solutions are associated with maximal UF at the beginning of the dwell, when osmotic forces are greatest. As the dwell progresses, however, glucose is absorbed and the rate of UF declines as the osmotic gradient is diminished, ultimately leading to negative net UF.
In contrast, icodextrin is able to maintain osmotic forces over extended periods of time. As a high molecular weight colloid osmotic agent, icodextrin does not readily diffuse across the peritoneal membrane but rather is slowly removed from the peritoneal cavity via lymphatic absorption. This results in sustained UF and solute clearance over longer dwell periods compared with dextrose-based solutions.1-3
Ho-Dac-Pannekeet et al. Kidney Int 1996;50:979-86; Douma et al. Kidney Int 1998;53: ; Mujais S et al. Kidney Int 2002; 62(Suppl 81): S17-S22
1Ho-Dac-Pannekeet MM, Schouten N, Langendijk MJ, et al. Peritoneal transport characteristics with glucose polymer based dialysate. Kidney Int. 1996;50:
2Douma CE, Hiralall JK, Waart DR, Struijk DG, Krediet RT. Icodextrin with nitroprusside increases ultrafiltration and peritoneal transport during long CAPD dwells. Kidney Int. 1998;53:
3Mujais S, Vonesh E, Moberly J. Clinical physiologic correlates of ultrafiltration in peritoneal dialysis. Kidney Int. In press.
4Rippe B, Levin L. Computer simulations of ultrafiltration profiles for an icodextrin-based peritoneal fluid in CAPD. Kidney Int. 2000;57:

46. 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

47. 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

48. 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

49. Management of Type 2 UF Failure
Use loop diuretics in patients with RRF
Majority, transfer to HD permanently

50. Thank you