Transcript Diapositiva 1 - acropolismed.it

EPS: Il Dibattito
Il Mito
Roberto Corciulo
Divisione di Nefrologia e Dialisi
Azienda Ospedaliero Policlinico
Università di Bari
Simposio
Bari, 18 marzo 2010
CAPD and its diffusion
CAPD originated in Austin, Texas, in 1975, when Robert Popovich and
Jack Moncrief discussed ways to dialyze a patient who was unable to
undergo hemodialysis.
The initial announcements of their clinical findings were not taken
seriously.
But when Popovich and Moncrief presented further clinical successes in
1978, the medical community was convinced. Compared to intermittent
procedures, the methods they developed made it possible to remove
fluids and filter the blood more steadily and continuously.
CAPD and its diffusion
1232
1400
8000
1200
7000
1000
6000
800
34% of the total dialysis population
5000
600
12% of the total dialysis population
4000
1700
3000
400
2000
200
1000
0
20
0
1978
1979
1980
1981
1977
1982
1980
1983
1837
2000
1800
1600
n. pts on PD
n. pts on PD
8532
9000
2141
1400
1200
1000
800
600
400
200
0
1978
1980
1981
1982
Nolph KD et al, Kidney Int. 1985; 28:198:205
Posen G et al, 1983; 4° ISAO Official Satellite Symp on CAPD Kyoto
Wing AJ et al, Proc. Eur Dial Transpl Assoc. 1983; 20:5-67
Encapsulating Peritoneal Sclerosis (EPS) and PD
The first description of this complication in patients on peritoneal dialysis
was published in 1980 (Denis J et al) and subsequently Gandhi and
collegues reported 5 patients who showed sclerotic thickening of the
peritoneal membrane.
The authors listed these factors as
potentially
important
to
the
development of the complication:
peritonitis,
hypertonic
dextrose
solution, low pH of the dialysis
solution, and dissolved plasticizers
from the solution container.
Denis J et al, Ann Intern Med 1980; 93:508
Gandhi VC et al, Arch Intern Med 1980; 140:1201:3
Peritoneal sclerosis.
A 'sword of Democles' for
peritoneal dialysis?
Schmidt RW, Blumenkrantz M Arch
Intern Med. 1981 Sep;141(10):1265-7.
The
birth
of
the
“myth”
The disease is defined as an:
Inflammatory process transforming
the peritoneal membrane into thick
fibrous tissue, surrounding and
compressing bowel loops. At
laparoscopy the small bowel was
enclosed in a bag or “cocoon” of
thickened peritoneum.
Richard Westall (1812)
EPS – First Links to Peritoneal Dialysis
In 1983, Slingeneyer described sclerosing peritonitis that occurred within
a few weeks to several years after peritoneal dialysis (PD) discontinuation.
In the report, the authors described an overall sclerosing peritonitis
incidence of 1.4% (6/431). The authors emphasized that this rare, “lifethreatening” complication involved asymptomatic peritoneal thickening
and destruction of the mesothelial layer, associated with a loss of
ultrafiltration (UF). They cautioned that the peritoneum, a living
membrane, was altered more dramatically during long-term PD.
Subsequently, in 1985, Slingeneyer and Elie published the results of an
international survey of SEP in 59 cases.
Slingeneyer A et al, Trans Am Soc Artif Intern Organs 1983; 29:633–40.
Slingeneyer A, Elie M. Adv Perit Dial. 1985. Proc. of the Fifth Annual CAPD
Conference, Missouri. University of Toronto Press, Toronto, 1985:118
Cooperative International Study on Sclerosing
Encapsulating Peritonitis: Preliminary Report
n. 59 cases of EPS
8
4
7
Pts with SEP
6
Incidence/year of peritonitis
for each group of patients
5
3
4
2
3
2
1
1
0
<1
1-1,5 1,5-2 2-2,5 2,5-3 3-3,5 3,5-4
Time of diagnosis
4-5
>5
Incidence/year of peritonitis
Patients with SEP
years
……SEP appars to be a multifactional complication, but, five factors seem predominate:
recurrence and severity of peritonitis, time exposure to peritoneal dialysis, antiseptics,
solution buffer and the use of betablockers.
Adapted from A. Slingeneyer, M. Elie Adv Perit Dial 1985; 1:118
The potential risk factors of EPS
Between August 1978 and December 1983, 163 patients (104 males and
59 females) were trained in CAPD in the hospital de la Pitie in Paris.
Twelve patients (6 males and 6 females) developed the complication for
an incidence of one case of SEP for 16.6 patient/years (7,3%)
66,6%
Rottembourg J et al, Adv CAPD 1985; 1:109–17.
The potential risk factors of EPS
(acetate)
(acetate)
(lactate)
(lactate)
The AA. demonstrated that the use of acetate solution was the predominant cause of
two outstanding abnormalities: UF loss and morphologic changes in the p.m.
Rottembourg J et al, Adv CAPD 1985; 1:109–17.
Sclerosing peritonitis:
the contribution of chlorhexidine
11/162 pts (6,7%)
System
Spray
No. of
patients
Peritonitis rate
(pat/ months
per episode)
Sclerosing
peritonitis
Group I
Fresenius
Chlorhexidine
in alcohol
54
6,3
11
Group II
Travenol
Povidone
iodine
43
7,8
0
Group III
Fresenius
Povidone
65
7,0
0
To prevent possible longterm complications such as sclerosing peritonitis should avoid
the introduction into the peritoneal cavity of any unnecessary substance and in
particular chlorhexidine in alcohol.
Junor BJR et al, Perit Dial Bull 1985; 5:101
Case-Control Study to determine
the cause of EPS
The EDTA Registry, in 1985, carried out a case control study to determine the cause of EPS.
162 patients, either alive or dead, with SEP diagnosed until the end of 1984
92 cases (57%) without cocoon; 70 cases (43%) with cocoon; 55 cases for Case-control
Study.The mean interval between first peritoneal dialysis and diagnosis of sclerosing
peritoneal disease was 30.1 (SD 16) months with a range of 6-78 months.
Analysis using Mc Nemar’s test
Oulès R. et al Nephrol Dial Transplant (1988) 3: 66-69
Advances in
Peritoneal Dialysis
Vol. 1 - 1985
Part four: Ultrafiltration Failure and Peritoneal Sclerosis
Peritoneal Sclerosis and Ultrafiltration Following 3 Months of CAPD in a Small Animal
Model.
L.H. Nielsen, K.D. Nolph, R. Khanna, H. Moore
Page: lOO
Sclerosing Peritonitis -An Experimental Study.
lain Henderson, L. Wilson, M. Wallace, L. W. Dobbie
Page: 107
Loss of Ultrafiltration and Sclerosing Encapsulating Peritonitis During CAPD. Evaluation of
the Potential Risk Factors.
1. Rottembourg, B.lssad, P. Langlois, B. Tranbaloc, A. Adamou, F. DeGroc, M. Legrain
Page: 109
Cooperative International Study on Sclerosing Encapsulating Peritonitis: Preliminary
Report.
A. Slingeneyer, M. Elie
Page: 118
Historical focus of EPS’s risk factors
10
Diagnosis of EPS
(mean of years)
8
6
4
Acetate,
Chlorhexidine,
Peritonitis
2
0
Risk 1.9/1000
Incidence 1,4 -7,3%
duration 21,5 mos
epis. perit. 2,03/y1
1980
1
Pusateri R.et al Am J Kidney Dis 1986; 1:56
1988
EPS
Refining pathogenesis and risk factors
In 1992, Dobbie described a syndrome of peritoneal fibrosis and sclerosis
in PD patients that was characterized by a “tanned peritoneum.”
The tanning of the peritoneum was believed to consist of degradation
products of fibrin, collagen, and other protein components, possibly
caused by nonenzymatic glycosylation of glucose in the dialysis solution.
Induction of potent intraperitoneal molecules such as interleukins and
growth factors by glucose degradation products might promote fibrosis,
new membrane formation, and adhesions.
The mesothelial monolayer and subjacent stroma were critically involved
in the progression of fibrosis, and that loss of mesothelium might result
from long-term exposure to bioincompatible dialysis solution, with or
without antiseptic agents or bacterial infection also being involved.
Dobbie JW , Perit Dial Int, 1992; Vol. 12, pp. 14-27
Recommendations on preventing EPS
1.Early removal of catheter in severe peritonitis, since all evidence points
to a continuing "scalded“ peritoneum lesion where mesothelium refuses
to recover the surface.
2. Reduction in the exposure of the naked stroma to the effects of
hypertonic dialysate.
3. Resting the peritoneum from dialysis where clinically feasible, and
allowing remesothelialization to occur naturally as early as possible.
Although CAPD can be used for many years without any significant
structural damage, for a safer future, effort should be concentrated in
providing a glucose-free physiological and emollient dialysate for the
acute and healing phase in severe peritonitis.
Dobbie JW, Perit Dial Int;1992, Vol. 12, pp. 14-27
EPS
Refining pathogenesis and risk factors
In 1994 Campbell performed a cross- sectional study of 15 patients: five had
died of sclerosing peritonitis, four had stopped peritoneal dialysis because
sclerosing peritonitis was suspected, and six were considered to be at
increased risk because of more than 4 years on peritoneal dialysis.
The duration of dialysis, number of episodes of peritonitis, strength of
peritoneal dialysis bags, the type of dialysate, and the use of beta blockers.
were examined.
Of the clinical features, only duration of dialysis could be shown to be an
important risk factor (five of the six patients with certain sclerosing
peritonitis had been on PD for 7 or more years) .
Campbell S. et al, Am J Kidney Dis 1994; 5:819-25
Identification of risk factors
Case No.
Status
Age yr
Sex
No. of months on
CAPD
No. of episodes of
peritonitis
1
deceased
26
F
84
5
2
deceased
61
F
27
1
3
deceased
44
F
96
5
4
deceased
25
F
97
10
5
deceased
37
F
115
5
6
suspected
42
F
111
5
7
suspected
51
M
71
3
8
suspected
41
F
54
1
9
suspected
51
F
61
4
10
at risk
53
F
112
9
11
at risk
54
F
102
5
12
at risk
76
M
85
5
13
at risk
44
F
49
2
14
at risk
70
F
49
4
15
at risk
69
F
48
6
77,4 + 28
4,6 + 2,4
mean
Campbell S. et al, Am J Kidney Dis 1994; 5:819-25
EPS
Refining pathogenesis and risk factors
Sixteen patients (11 men, 5 women) with PS were investigated with
regard to demography, clinical features, risk factors, treatment, and
outcome.
The time between the start of PD and the time the diagnosis of PS was
made was 70 months (range 40 -147 months).
The time interval between discontinuation of PD and the diagnosis was
21 months (range 5 -50 months) in 6 patients. In 4 of these patients, it
was preceded by renal transplantation, in the other 2 by transfer to
hemodialysis because of either persistent peritonitis, or ultrafiltration
failure.
All patients used lactate-buffered dialysis solutions without disinfectants
such as chlorhexidine.
P. Hendricks et al, Perit Dial Int 1997; 17:136-143
Demographic data and risk factors
in patients with EPS
81%
modified P. Hendricks et al, Perit Dial Int 1997; 17:136-143
EPS and risk factors
A relation of PS with severe peritonitis
may be present in some patients.
Peritoneal sclerosis is a complication of
long-duration PD and could also
become manifest after a successful
renal transplant.
Patients with PS had lower net
ultrafiltration and higher transport rates
compared to controls who were
Peritoneal sclerosis
matched for duration of PD.
Glucose exposure is likely to be an important risk factor for PS.
Controls
P. Hendricks et al, Perit Dial Int 1997; 17:136-143
Historical focus of EPS’s risk factors
10
Long-term treatment,
Severe Peritonitis,
Glucose exposure
Diagnosis of EPS
(mean of years)
8
6
4
Acetate,
Chlorhexidine,
Peritonitis
2
0
Incidence 1,4 -7,3%
duration 21,5 mos
epis. perit. 2,03/y1
1980
1Pusateri
1988
R.et al Am J Kidney Dis 1986; 1:56
2Campbell S. et al, Am J Kidney Dis 1994; 5:819-25
3Hendricks P. et al, Perit Dial Int 1997; 17:136-143
incidence 0.9%
duration 70,5 mos2,3
epis. perit. 1,33/y2,3
1996
A Report of the Japanese Sclerosing
Encapsulating Peritonitis Study Group
Among 6,923 patients undergoing CAPD between 1980
and 1994, 62 (0.9%) given CAPD developed SEP.
14
13
n. of patients
12
11
10
9
8
8
6
6
4
4
2
1
3
3
3
86
87
88
1
0
82
83
84
85
89
90
91
92
93
94
year
Yasuo Nomoto et coll., Am J of Kidney Disease, vol.28, 3 1996, 420-27
A Report of the Japanese Sclerosing Encapsulating
Peritonitis Study Group
These 62 pts developed EPS
10 to 138 months (average 65,4 months) after
starting CAPD
Peritonitis incidence was one episode every 20.0 months in the 62 patients
with EPS during the study period. In contrast, peritonitis incidence was one
episode every 32.4 months in control patients.
5 of 62 patients with EPS had no history of peritonitis. The mechanism of the
development of EPS without peritonitis is uncertain. It was suggested that
aberrations of the host defense mechanism might play an important role in the
development of EPS in PD patients.
Incidence of EPS is lower in CAPD patients in Japan. One possible reason is
that racial differences might play a role in the development of EPS in CAPD.
Yasuo Nomoto et coll., Am J of Kidney Disease, vol.28, 3 1996, 420-27
EPS: the experience in Australia
n.54/7374 pts (1978-1994)
1,9
4,2
Russel J.Rigby et coll., Nephrol Dial Transplant (1998) 13: 154-59
Prevalence of sclerosing peritonitis in Australia
n.7374 pts (1978-1994)
25
% of patients
20
19,4%
54 patients with EPS were analysed
(overall prevalence was 0.7%)
15
10
5
0
<1
>1
>2
>3
>4
>5
>6
>7
>8
>9
Duration in years of continuous peritoneal dialysis
Russel J.Rigby et coll., Nephrol Dial Transplant (1998) 13: 154-59
EPS: the experience in Australia
n.7374 pts (1978-1994)
The
median duration of peritoneal dialysis treatment was 48
months for patients developing sclerosing peritonitis.
With a reduction in the peritonitis rate over this period, one have
expected the incidence to decrease.
Further evidence that the duration of treatment is a major risk
factor for the development of sclerosing peritonitis is the increase in
the prevalence of the disease with duration of treatment, reaching
20% after 9 years of continuous dialysis.
Russel J.Rigby et coll., Nephrol Dial Transplant (1998) 13: 154-59
Historical focus of EPS’s risk factors
10
Long-term treatment,
Severe Peritonitis,
Glucose exposure
Diagnosis of EPS
(mean of years)
8
6
4
2
0
Acetate,
Chlorhexidine,
Peritonitis
Incidence 1,4 -7,3%
duration 21,5 mos
epis. perit. 2,03/y1
1980
1Pusateri
Duration of PD,
Frequent and Severe
Peritonitis,
Glucose exposure
1988
R.et al Am J Kidney Dis 1986; 1:56
2Campbell S. et al, Am J Kidney Dis 1994; 5:819
3 Hendricks P. et al, Perit Dial Int 1997; 17:136
Risk 1,9-4.2/10004
incidence 0.5-0.8%4,5,6
duration 48-65,4 mos4,5,6
epis. perit. 1,66/y5
incidence 0.9%
duration 77,5 mos2,3
epis. perit. 1,33/y2,3
1996
4RJ.Rigby
1998
et al., NDT, 1998; 13: 154
Y Nomoto et al., Am J of Kidney Dis, vol.28, 3 1996, 420
6 Afthentopoulos IE et al., Adv Ren Replace Ther. 1998 Jul;5(3):157-67.
5
Peritoneal dialysis before the new millennium
After more than 20 years’ experience of PD, supported only by
retrospective clinical studies, PD-related EPS was considered an
iatrogenic complication .
Duration of PD, exposure to dialysis solutions with high glucose
EPS: a time-dipendent complication
concentrations, and frequent and severe peritonitis are considered
to be risk factors and no one has yet identified the mechanisms for
EPS development.
EPS
Refining epidemiological study and
histomorphological changes
Am J Kidney Dis, 2004; 44:729-737.
Clin J Am Soc Nephrol 4: 1222–1229, 2009
1999;15:185-92
Garosi G, Di Paolo N.
Peritoneal Sclerosis – An overview
Peritoneal
EPSsclerosis.
:
A “sword
complication
stillof
able to
Democles”
for
influence
clinical
decisions
anddialysis?
therefore
peritoneal
to limit the use of
peritoneal dialysis ?