Peritoneal dialysis by Dr. Basil Tumaini, prepared for nephrology lecture during the residency in Internal medicine at Muhimbili University of Health and Allied Sciences

1. PERITONEAL DIALYSIS (PD)
Dr. Basil Tumaini
MD, MMED Resident
12 July 2017
Muhimbili University of Health and Allied Sciences

2. Introduction
• The dialysis modality of 11% of patients
worldwide
• The proportion varies:
 < 5% in Japan
 > 60% in Mexico

3. Principle of PD Treatment

4. PERITONEAL DIALYSIS
• 1.5 – 3L of a dextrose-containing solution is
infused into the peritoneal cavity and allowed
to dwell for a set period, usually 2-4 hours
• Toxic material are removed through a
combination of convective clearance
generated through ultrafiltration and diffusive
clearance down a concentration gradient

5. PD
• Rate of diffusion diminishes with time and
eventually stops when equilibration between
plasma and dialysate is reached

6. PD
• Absorption of solutes and water from the
peritoneal cavity occurs across the peritoneal
membrane into the peritoneal capillary
circulation and via peritoneal lymphatics into
the peritoneal lymphatic circulation
• The rate of solute transport may be altered by
presence of infection (peritonitis), drugs and
physical factors such as position and exercise

7. • Abdominal cavity is lined by peritoneal membrane
which acts as a semi-permeable membrane
• Diffusion of solutes (urea, creatinine, …) from blood
into the dialysate contained in the abdominal cavity
• Removal of excess water (ultrafiltration) due to
osmotic gradient generated by glucose in dialysate

8. The semi-permeable dialysis membrane of the peritoneum
• Comprises the capillary endothelium,
supporting matrix and the peritoneal
mesothelium
• Fluid and solutes move between the fluid-
filled peritoneum and blood via what is
termed, the ‘ three-pore model ’ of PD
– Large pores
– Small pores
– Ultrasmall pores

9. The semi-permeable dialysis membrane of the peritoneum …
• Large pores (20 – 40nm): allow macro-
molecules such as proteins, to be filtered
between compartments (effectively via
venular or lymphatic absorption)
• Small pores (4 – 6nm) : responsible for the
transport of small solutes such as sodium,
potassium, urea and creatinine
• Ultrasmall pores (<0.8nm) : transport water
alone (shown to be aquaporin 1)

10. The net movement of solutes, such as urea, will depend on
• Net diffusion through small pores and
convection through large pores
• Total volume of dialysate infused
• Net fluid ultrafiltration (or, under certain
circumstances, absorption)

11. Ultrafiltration (UF)
• The net movement of water relies on:
– Presence of a high intraperitoneal osmotic
gradient (generated by glucose) or
– Presence of a high intraperitoneal oncotic
gradient (generated by glucose polymers, such as
icodextrin)

12. Ultrafiltration (UF) …
The osmotic gradient is usually generated by
glucose and depends on:
– The glucose concentration of the dialysate
– A patient’s blood glucose
– The rate of absorption of glucose itself from PD
fluid

13. Ultrafiltration (UF) …
• UF is optimized by:
– Ensuring normoglycaemia (relevant for diabetic
patients)
– Adjusting the tonicity of the PD solution (glucose
concentration)
– Altering the duration of each dialysis dwell.
– Adjusting dwell volumes; ↑ volume often (but not
always) leads to ↑ UF

14. DIALYSATE
• Primarily consists of water, osmotic agents
(e.g. dextrose), electrolytes and minerals
• Preformed dialysis solutions are available
typically ranging from 1.5 – 3L
• Lactate is the preferred buffer in peritoneal
dialysis solutions, to control acidosis

15. DIALYSATE
• Most common additives:
– Heparin to prevent obstruction of dialysis catheter
lumen with fibrin
– Antibiotics to prevent infections.
– Insulin may be added in patients with diabetes
mellitus

16. PERITONEAL DIALYSATE
• Peritoneal dialysate needs to
– remove uremic toxins
– normalize electrolytes
– correct acidosis
– remove fluid.
• Ideally fluid should be compatible with long-
term peritoneal health

17. PERITONEAL DIALYSATE …
• Volume: usually 2L but 1.5, 2.5, or 3L also
available
• Glucose concentration: three standard
concentrations, usually about 1.5, 2.5 and 4.0%
(roughly 25g, 50g, and 75g glucose per bag)
• Sodium: Na + 135mmol/L (although lower
concentrations may improve salt, and thus water,
removal)
• Other electrolytes: Ca2+ ranges from 1.25 to
1.75mmol/L and 0.25mmol/L of Mg

18. PERITONEAL DIALYSATE …
• Buffer: bicarbonate is not compatible for storage
with calcium and Mg in PD bags, so lactate
(which is rapidly converted to bicarbonate in the
liver) is widely used instead, at 35 – 40mmol/L
e.g. in Dianeal®
• Newer solutions may contain:
– Bicarbonate alone or in combination with lactate as
buffer (using bags mixed immediately pre-infusion)
– Icodextrin (for an oncotic gradient), rather than
glucose (as an osmotic gradient), to achieve UF
– Amino acids as nutritional supplement !

19. PERITONEAL DIALYSATE …
• Avoiding peritoneal glucose exposure
– High peritoneal glucose exposure over time (often
years) predicts the development of UF failure, and
causality has been suggested
– An alternative to glucose-containing dialysate is
icodextrin (Extraneal ®)
– Icodextrin is a 20-glucose polymer with potent
colloidal effects (similar to albumin)

20. PERITONEAL DIALYSATE …
• Avoiding peritoneal glucose exposure …
– Icodextrin is particularly suited to high
transporters
– It acts at the small intercellular pores and is only
slowly lost from the peritoneal cavity, meaning
that the oncotic gradient is maintained
– It therefore produces gradual and sustained UF
over long dwell periods (overnight dwell in CAPD
or daytime dwell in APD)

21. Biocompatible solutions
• PD fluid is sterilized through heat treatment
• During the process, at the pH of lactate-based
glucose solutions, glucose degradation
products (GDP) and advanced glycation end-
products (AGE) are formed
• These are believed to damage the peritoneal
membrane leading to fibrosis

22. Biocompatible solutions
• Biocompatible solutions have been developed
to ameliorate this and retrospective analysis
of registry data suggested better patient
survival
• Definitive evidence is lacking

23. ACCESS TO PERITONEAL CAVITY
• Obtained through peritoneal catheter (e.g., a
Tenckhoff Catheter)
• Catheters used for maintenance peritoneal
dialysis are flexible, being made of silicon
rubber with numerous side holes at the distal
end
• As with hemodialysis, optimal dose of
peritoneal dialysis is unknown

24. Types of PD Catheters
• Overall PD catheter survival : +/- 90% at 1 year
• No particular catheter is superior

25. Placement of Peritoneal Dialysis
Catheter

26. PD Catheter Exit Site

27. Peritoneal Dialysis (PD)
PD
Continuous Intermittent

28. Continuous PD Regimens
Multiple sequential exchanges are performed during the day
and night so that dialysis occurs 24 hours a day, 7 days a week
CAPD: Continuous
Ambulatory PD
CCPD: Continuous
Cyclic PD

29. FORMS OF PERITONEAL DIALYSIS
• Peritoneal dialysis may be carried out as:
– Continuous Ambulatory Peritoneal Dialysis (CAPD)
– Continuous Cyclic Peritoneal Dialysis (CCPD) or
– A combination of both

30. FORMS OF PERITONEAL DIALYSIS
• CAPD
– dialysis solution is manually infused into the
peritoneum and exchanged 3 - 5 times daily
• APD/ NIPD/CCPD
– exchanges are performed in an automated
fashion, usually at night.
– The patient is connected to an automated cycler

31. Forms of PD

32. CCPD Treatment Setup

33. FORMS OF PERITONEAL DIALYSIS

34. Intermittent PD Regimens
PD is performed every day but only during certain hours
DAPD: Daytime
Ambulatory PD.
Multiple manual exchanges
during waking hours
NPD: Nightly PD.
Performed while patient
asleep using an automated
cycler machine.
Sometimes,
1 or 2 day-time manual
exchanges are added to
enhance solute clearances

35. ILLUSTRATION

36. Advantages of PD
• Preservation of residual renal function.
• No need for vascular access.
• Mobility (e.g. easy to transport dialysis to
holiday destinations).
• Patient engagement in treatment.
• Home-based therapy — maintains patient
independence.
• Less expensive than HD.
• Less risk of transmission of blood-borne
viruses.

37. Question 2
• What is the most common cause of
technique failure in peritoneal dialysis?
(choose one answer):
1. Ultrafiltration failure
2. Malnutrition
3. Peritonitis
4. Non-adherence to the treatment regimen

38. COMPLICATIONS OF PD
• Peritonitis
• Catheter-associated non-peritonitis infections
• Catheter-associated noninfectious
complications
• Metabolic disturbances
• Residual uremia

39. Peritonitis
• Usually occurs when there is break of aseptic
technique during exchanges
• Defined as elevated peritoneal fluid leukocyte
count (100/mm3, with at least 50% PMNs)
• Clinically there is fever, pain and cloudy
dialysate
• Common culprits are gram-positive cocci
• Managed with intraperitoneal or oral antibiotics
• If gram-negative rods or yeast are involved, catheter
removal is usually required

40. Risk factors
• T2DM, other significant comorbibity.
• Catheter type and implantation technique.
• Connection systems.
• Nasal carriage of Staphylococcus aureus .

41. Clinical features
• Abdominal pain, nausea, and vomiting
• ‘ Cloudy ’ PD effluent is very highly suggestive
• High fever, systemic sepsis with signs of an
ileus, and peritonism may be present
• Patients should be taught to report cloudy
effluent immediately
• Always consider other causes of peritonitis
(e.g. perforation, strangulated hernia, etc.)

42. Diagnosis
• PD fluid for microscopy and Gram stain:
– Preferably after dwell time of 4h
– >100 WBC/mm 3 (>50% neutrophils)
– Microscopy and culture of PD fluid (discuss with
microbiology) and blood
– FBC ( ↑ WCC) and ↑ CRP
• Abdominal pain can be severe. Rapid peritoneal
flushing can improve symptoms, but samples
from the original cloudy bag should be sent for
microbiology (and rapid flushing should be
avoided once IP antibiotics have been
administered)

43. Bacteriology
• Gram +ve cocci: 45 – 75% (coagulase-negative
staphylococci, S. Aureus)
– often introduced after touch contamination of the
connections or following catheter exit site
infection
– Colonization of catheter
– biofilms can lead to recurrence of peritonitis and
necessitate catheter exchange

44. • Gram –ve organisms: 15 – 25% e.g.,
Pseudomonas, coliforms.
– Usually of bowel origin
– Air in the peritoneum is common and may not
indicate bowel perforation
– Suspect perforation if mixed organisms on culture,
and arrange appropriate imaging and/or
exploration

45. • Culture negative or ‘no growth’: ideally,
cultures should be positive in >85% cases
• Higher yields may be obtained by inoculating
blood culture bottles with PD fluid

46. • Mycobacterial infections: 1%
– Consider in patients with culture-negative
– peritonitis not responding to empiric antibiotic
therapy
– Smears of PD effluent are rarely positive for acid-
fast bacilli, and diagnosis is usually made on
culture (6-week) or at laparoscopy/otomy, with
confirmation on peritoneal biopsy.

47. • Fungal: 3%
– Usually Candida spp.
– Peritonitis is infrequent but has a poor prognosis.
It often follows antibiotic therapy in at-risk
(e.g.malnourished) patients
– PD catheter removal is mandatory
Allergic peritonitis e.g. to icodextrin may also
occur

48. Management of peritonitis
• Initiate empiric antibiotics promptly
– GP: Vancomycin 2g IP on day 1, with a further
dose on days 3 – 7, or a cephalosporin
– GN: cover with an aminoglycoside or third-
generation cephalosporin
• IP administration is more effective than IV

49. Catheter-associated nonperitonitis infections
• Often termed tunnel infections
• Usually caused by S. aureus , Pseudomonas
• The use of prophylactic topical exit site ointment
(e.g. mupirocin) reduces such infections
• Can be managed with local antibiotic or silver
nitrate administration
• May require parenteral antibiotics and catheter
removal (start flucloxacillin 500mg PO qid or
ciprofloxacin 500mg PO bd for 14/7 if there is a
history of Gram – ve infection)

50. Catheter-associated noninfectious complications
• Outflow failure
• Pericatheter leak
• Abdominal wall herniation
• Catheter cuff excursion and intestinal
perforation

51. Metabolic Disturbances
• Hypoproteinemia from loss of albumin and
other proteins obligates a high protein diet
• Hyperglycemia and weight gain due to
absorption of several calories of dextrose
and therefore can lead to other
complications of insulin resistance
• Due to continuous removal of phosphorus
and potassium, a more liberal diet is
allowed

52. Residual uremia
• Particularly in patients with no residual kidney
function

53. Switching from PD to HD
• There was a decline in PD utilization,
threatening the viability of PD programs
• About 25% of PD patients switched to HD in
5-7 years, >70% of the switch occurring in the
first 2 years
• Commonest causes of the switch were
infections, fluid overload due to ultrafitration
failure, abdominal surgery and malnutrition
Jaar BG, Plantinga LC, Crews DC, Fink NE, Hebah N, Coresh J, Kliger AS, Powe NR. Timing, causes,
predictors and prognosis of switching from peritoneal dialysis to hemodialysis: a prospective
study. BMC nephrology. 2009 Feb 6;10(1):3.

54. PD adequacy: beyond calculation
• Absence of uremic symptoms
• Nutritional status, appetite, weight, serum
albumin
• Fluid status
• Quality of life (e.g. by subjective global
assessment scoring)
• Improved biochemistry and correction of the
complications of uraemia, such as anaemia

55. Switching from PD to HD …
• Independent predictors of the switch to HD
included higher BMI and black race
• No significant difference on the survival
between PD patients who switched to HD
compared to those who remained on PD
Jaar BG, Plantinga LC, Crews DC, Fink NE, Hebah N, Coresh J, Kliger AS, Powe NR. Timing, causes,
predictors and prognosis of switching from peritoneal dialysis to hemodialysis: a prospective
study. BMC nephrology. 2009 Feb 6;10(1):3.

56. WHICH MODALITY OT CHOOSE
• Selection of which dialysis modality is driven
by
– Patient’s choice
– Medical or social contraindication

57. Absolute contraindications to HD
• Thrombosed central veins
• Severe angina
• Hypotensive heart failure

58. Relative Contraindications to HD
• Long distance from HD unit
• Severe vascular disease
• Active diabetic retinopathy

59. Factors Influencing Dialysis Choice
Dialysis Modality
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Late Referral,
…

60. Absolute Contraindications for PD
• Colostomy, ileostomy, ileal conduit
• Abdominal wall infections or intra-abdominal sepsis,
e.g., active diverticular disease
• Inguinal, umbilical or diaphragmatic hernias (esp.
pleuroperitoneal leak)
• Intra-abdominal adhesions ?absolute vs relative
• Morbid obesity (inadequate clearance) ?absolute vs
relative
• Very poor housing
• No spare space in home
• Poor personal hygiene

61. Relative Contraindications for PD
• Frailty/dementia ?absolute vs relative
• Huge polycystic kidneys (insuffiecient
intraperitoneal space)
• Severe gastroparesis (worsening vomiting)
• Severe lung disease (diaphragmatic splinting)

62. Absolute contraindications for PD
• Documented loss of peritoneal function or
extensive abdominal adhesions (previous abd.
Surgeries)  limit dialysate flow
• Uncorrectable mechanical defects
(e.g., diaphragmatic hernia)
• In the absence of a suitable assistant, a
patient who is physically or mentally incapable
of performing PD.
NKF K/DOQI Guidelines 2000

63. Peritoneal Adhesions

64. Factors Influencing Dialysis Choice
Dialysis Modality
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Late Referral,
…

65. Best Study Design to Compare Dialysis
Modalities
• Prospective, randomized, clinical trial
• Significant barriers to performing this type of study1
• We are left with the analysis of observational data
from well-conducted prospective studies
1Korevaar JC et al. KI 2003; 64(6): 2222-2228

66. Quinn RR et al. 2011 (I)
Country: Ontario, Canada
Enrollment Years: 7-1-1998 to 3-31-2006
Follow-Up: 8 years
Population Type: Incident – Elective Outpatient
(databases @ Institute for Clinical
Evaluative Sciences)
Sample Size: HD: 4,538 PD: 2,035
Switching Modality: No
Model(s) Intention-to-Treat (baseline
modality)
Quinn RR et al. J Am Soc Nephrol 2011; 22: 1534-1542

67. • Several studies have suggested that the RR of
death on PD as compared with HD increases
over time
• This study showed that PD and HD are
associated with similar survival in incident
dialysis patients who have at least 4 months
of predialysis care and start therapy
electively as outpatients
Quinn RR, Hux JE, Oliver MJ, Austin PC, Tonelli M, Laupacis A. Selection bias explains apparent
differential mortality between dialysis modalities. Journal of the American Society of
Nephrology. 2011 Aug 1;22(8):1534-42.

68. • In contrast, when definitions of chronic dialysis
that have been traditionally used to study the
effect of dialysis modality on mortality were
used, the RR of death on PD compared with HD
increased over time, which is consistent with
previous studies
• The association disappeared after excluding
patients who started dialysis therapy urgently
suggesting the apparent benefit to be due to bias
Quinn RR, Hux JE, Oliver MJ, Austin PC, Tonelli M, Laupacis A. Selection bias explains apparent
differential mortality between dialysis modalities. Journal of the American Society of
Nephrology. 2011 Aug 1;22(8):1534-42.

69. Adjusted Survival between PD and HD,
(received > 4 months of predialysis care and
Started as outpatient)
Quinn RR et al. J Am Soc Nephrol 2011; 22: 1534-1542
Adjusted HR: 0.96, p = 0.44

70. Biases
• Residual confounding: limited adjustment for
known factors associated with mortality (e.g.,
comorbidities, lab data [albumin, …])
• Short follow-up (1-2 years) in some studies
• Lead-time bias: baseline GFR
• Selection bias: patient characteristics
• Statistical Methodology:
– Center Effect: confounding by clinic as patient
characteristics varied by center and treatment
– How to handle modality switching: As-Treated
vs Intention-to-Treat
• No causal relationship, just association!

71. Other Issues: PD vs HD
Beyond Survival
• In considering choice of dialysis technique,
other issues must be considered …

72. Factors Influencing Dialysis Choice
Dialysis Modality
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Cost of Care,
Late Referral,
…

73. Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study
• PD patients reported better QOL than HD patients in the
following domains:
– Bodily pain
– Travel
– Diet restrictions
– Dialysis access
– Financial well-being
– Physical functioning (only at baseline, not at 1 year)
Wu AW, Fink NE, Marsh-Manzi JV, Meyer KB, Finkelstein FO, Chapman MM, Powe NR. Changes in
quality of life during hemodialysis and peritoneal dialysis treatment: generic and disease
specific measures. Journal of the American Society of Nephrology. 2004 Mar 1;15(3):743-53.

74. Choices for Healthy Outcomes in Caring for ESRD (CHOICE) Study
• At one year
– HD patients improved more on aspects of
general health-related QOL than patients on
PD
– HD patients had greater improvement on:
• Physical functioning
• Sexual functioning
• General health perceptions
Wu AW, Fink NE, Marsh-Manzi JV, Meyer KB, Finkelstein FO, Chapman MM, Powe NR. Changes in
quality of life during hemodialysis and peritoneal dialysis treatment: generic and disease
specific measures. Journal of the American Society of Nephrology. 2004 Mar 1;15(3):743-53.

75. Factors Influencing Dialysis Choice
Dialysis Modality
Contraindications
Survival
Quality of Life
Treatment Satisfaction
Other Factors:
Late Referral,
…

76. CHOICE - Treatment Satisfaction: PD
vs HD
• PD patients were significantly more likely to give
excellent ratings of dialysis care overall
compared to HD patients (85% vs 56%).
• Also PD patients were more likely to give excellent
ratings for specific aspects of care:
– information on choosing a dialysis modality
– information on fluid removal
– staff and nephrologist availability
– coordination with other physicians
– caring of nurses or staff
Rubin HR et al. JAMA 2004; 291: 697-703

77. Implications
• Each modality has distinct advantages or disadvantages
• Physicians should be as explicit as possible in
describing specific tradeoffs and attempt to elicit
individual preferences at start of dialysis
• Although there is no conclusive evidence that the
choice of PD or HD provide a specific survival
advantage:
– Better selection of PD patients (PD underutilized)
– PD patients should be monitored closely after the
2nd or 3rd year of dialysis
– Consider a “timely” transfer to HD (if or when PD
problems arise)

78. What is the best long-term treatment?
1. PD
2. HD in-center
3. HD home/
self-care
Ask the nephrology providers which dialysis modality they
would select if they had ESRD?

79. What is the best long-term treatment?
Opinion vs Reality
Ledebo I., Ronco C. NDT Plus 2008; 6:403-408
1. PD
2. HD in-center
3. HD home/
self-care

80. Question 3
• Which one of the following patient’s
characteristic or comorbidity is associated with
better overall outcome on dialysis (choose
one answer):
1.Diabetes Mellitus + end-organ damage
2.BMI > 30
3.Residual urine output of > 500 cc / day
4.Colon cancer
5.Early initiation of dialysis (eGFR > 15)

81. Comparison of dialysis modalities

82. Is Timing of Dialysis Initiation
Important in ESRD Patients?
(Controversial)

84. IDEAL Study: K–M Curves for Time to the
Initiation of Dialysis & for Time to Death
Cooper BA et al. N Engl J Med 2010;363:609-619
• Between July 2000 & November
2008
• Australia / New Zealand
• 828 adults
• Early start:
eGFR 10-14 cc/min
• Late start:
eGFR 5-7 cc/min
• mean age 60.4 years
• 542 men & 286 women
• 355 with diabetes
• Median follow-up 3.6 years

85. Implications
• A total of 75.9% of the patients in the late-start group
started dialysis when eGFR was > 7.0 cc/minute,
owing to the development of symptoms!
• In this study, planned early initiation of dialysis in
patients with stage V CKD was not associated with an
improvement in survival or clinical outcomes (QOL)
•  OK to delay initiation of dialysis (eGFR < 7-10 cc/min)
•  Dialysis initiation should be based upon clinical
factors (symptoms) rather than eGFR alone
Cooper BA et al. N Engl J Med 2010;363:609-619

86. Why is Residual Renal
Function Important in Dialysis
Patients?

87. Why is baseline residual renal function
important?
• Remaining GFR at start of dialysis make a
significant contribution to the removal of
potential uremic toxins
• Also facilitates regulation of fluid, electrolytes,
and may enhance nutritional status and QOL
• Offers survival advantage in both HD and PD
Suda T et al. Nephrol Dial Transplant 2000; 15: 396
Shemin D et al. Am J Kidney Dis 2001; 38: 85
Szeto C et al. Nephrol Dial Transplant 2003; 18: 977

88. Adjusted Hazard Ratio: 0.70 (0.52-0.93) p = 0.02
Shafi T., Jaar B., et al. Am J Kidney Dis. 2010;56:348-58
Cumulative Incidence of All-Cause Mortality in 579
HD Patients by Urine Status at 1 Year (CHOICE)

89. Implications
• Try to preserve residual renal function in
dialysis patients!
•  Less dietary restriction
•  Better quality of life
•  Better survival
• Try to avoid nephrotoxins if your dialysis
patient still makes urine!

90. RRT other than HD and PD
• Kidney transplant

91. The Future …

92. • Regenerative Medicine …
• Stem Cell Therapy …
• Wearable Artificial Kidney