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Peritoneal dialysis (PD) is an important option for renal replacement therapy

Introduction and hypothesis: Peritoneal dialysis (PD) is an important option for renal replacement therapy. Peritoneal sclerosis (PS) limits PD duration due to loss of ultrafiltration (UF) capacity, while about 3% of PD patients experience a condition termed encapsulating peritoneal sclerosis (EPS). In many fibrotic diseases reduced Extracellular matrix (ECM) breakdown due to lowered matrix metalloproteinase (MMP) activity occurs, often from over-expression of tissue inhibitors of MMP (TIMPs) that underlie fibrotic remodeling. Furthermore, recent application of 2D gel proteomics on peritoneal dialysis effluent (PDE) samples has identified several proteins that are elevated in patients with membrane damage. These observations have led to the hypothesis that: changes in proteins in PDE samples, in particular those associated with ECM breakdown have value as non-invasive biomarkers of PS and the switch to EPS. To test this hypothesis, PDE samples from 3 patient cohorts was analysed for ECM proteolytic activity. A range of ECM processing proteins and 3 proteins identified from previous proteomic studies of patients developing EPS (intellectin-1, dermatopontin and collagen α1 (I)) were analysed in PDE samples. Methods: Three patient cohorts were studied: two were from Sheffield Kidney Institute (SKI) that consisted of 32 spot PDE samples (SKI-1) that included 1 EPS patient & 51 PDE & plasma samples collected during a peritoneal equilibrium test (PET) with multiple dwell times in patients who did not have EPS (SKI-2). The third cohort consisted of 209 samples from the Global Fluid Study (GFS) including sequential samples from 12 EPS & 42 matched controls patients. MMP activity was assessed using the ENZchek assay system. Plasmin activity was assessed by using cleavage of the V0882 substrate. TIMPs, MMPs, intelectin-1, dermatopontin, and collagen (α1) I were quantified by commercial ELISA in PDE and plasma samples. PDE cytology (macrophages, leukocytes, fibroblasts and mesothelial cells) was performed to determine if changes in any protein could be associated with changes in cell types. Clinical data were recovered from either the peritoneal dialysis database (PDDB) at Sheffield or the GFS archives. The analysis was performed using Microsoft Excel 2010 software, SPSS, and Graphpad prism (prism 5. 01 for windows). Results: Plasmin activity in PDE samples decreases with long duration of PD therapy. Minimal MMP activity was found in all PDE samples. In the SKI-1 cohort, MMP-1, -9, & -13 were almost undetectable with only MMP-2 & -3 being measurable with levels of ((mean±SD) 46±37 & 2. 1±2. 2 ng/mL respectively). In contrast TIMP-1 and TIMP-2 and to lesser extent TIMP-3 had significant levels in PDE samples from commencing PD (109±88, 17±12, and 0. 28±0. 33 ng/mL respectively). All TIMPs & MMP-2 were raised in the single patient who had a diagnosis of EPS. In samples from the GFS cohort, there was a rapid 6 fold increases in TIMP-1 within 100 days of the diagnosis of EPS, which when normalised to TIMP-2 levels was a good predictor of EPS. Calculation of the plasma to dialysate transfer rate by reference to that of circulating proteins with no peritoneal production and of known molecular weight (albumin, beta2microglobulin (B2M), transferrin, IgG, and creatinine) demonstrated that TIMPs & MMPs (especially TIMP-1 and MMP-2) have significant peritoneal production. Plasma levels for TIMP-1, -2, MMP-2, -3, and intelectin-1 (mean±SD) were 121±27, 85±16, 176±35, 11±5, and 374±136 ng/mL in healthy individuals respectively. Plasma levels in PD patients for TIMP-1, -2, MMP-2, -3, and intelectin-1 (mean±SD) were 297±78, 158±33, 309±112, 42±28, and 749 ±722 ng/mL respectively. None of the proteins identified by proteomics as predictors of EPS were able to be validated by ELISA. However TIMP-1, -2, MMP-2, intelectin-1, and collagen (α1) I in PDE samples had significant correlations with the loss of ultrafiltration and thus membrane damage. PDE cytology showed that peritoneal fibroblast and leukocyte numbers increase with time on PD, while peritoneal macrophage decreases with time on PD. There were no significant changes in mesothelial cells. Conclusions: Negligible MMP activity in PDE samples results from high TIMP levels which could underlie the development of PS. The rapid increase in TIMP-1 within 100 days of EPS development offers value as a diagnostic tool or a late biomarker. Plasma levels of TIMP-1, 2, MMP-2, 3, and intelectin-1 are higher in patients on PD compare to healthy individuals. The increase in peritoneal fibroblasts may be a source of TIMP-1.
Introduction and hypothesis: Peritoneal dialysis (PD) is an
This phrase/word is too simple and can be replaced with:
important
option for renal replacement therapy. Peritoneal sclerosis (PS) limits PD duration due to loss of ultrafiltration (UF) capacity, while about 3% of PD
You use this word too often, consider replacing it with
patients
experience a condition termed encapsulating peritoneal sclerosis (EPS). In
This phrase/word is too simple and can be replaced with:
many
fibrotic diseases
This phrase/word (depending on the context) can be potentially replaced with :
reduced
Extracellular matrix (ECM) breakdown due to lowered matrix metalloproteinase (MMP)
You use this word too often, consider replacing it with
activity
occurs,
This phrase/word is too simple and can be replaced with:
often
from over-expression of tissue inhibitors of MMP (TIMPs) that underlie fibrotic remodeling.
Furthermore
, recent application of 2D gel proteomics on peritoneal dialysis effluent (PDE)
You use this word too often, consider replacing it with
samples
has identified several proteins that
are elevated
in
You use this word too often, consider replacing it with
patients
with membrane damage. These observations have led to the hypothesis that:
You use this word too often, consider replacing it with
changes
in proteins in PDE
You use this word too often, consider replacing it with
samples
,
in particular
those associated with ECM breakdown have value as non-invasive biomarkers of PS and the switch to EPS. To
This phrase/word (depending on the context) can be potentially replaced with :
test
this hypothesis, PDE
You use this word too often, consider replacing it with
samples
from 3
You use this word too often, consider replacing it with
patient
You use this word too often, consider replacing it with
cohorts
was analysed
for ECM proteolytic
You use this word too often, consider replacing it with
activity
. A range of ECM processing proteins and 3 proteins identified from previous proteomic studies of
You use this word too often, consider replacing it with
patients
developing EPS (intellectin-1, dermatopontin and collagen α1 (I))
were analysed
in PDE
You use this word too often, consider replacing it with
samples
. Methods: Three
You use this word too often, consider replacing it with
patient
You use this word too often, consider replacing it with
cohorts
were studied
: two were from Sheffield Kidney Institute (SKI) that consisted of 32 spot PDE
You use this word too often, consider replacing it with
samples
(SKI-1) that included 1 EPS
You use this word too often, consider replacing it with
patient
& 51 PDE &
You use this word too often, consider replacing it with
plasma
You use this word too often, consider replacing it with
samples
collected during a peritoneal equilibrium
This phrase/word (depending on the context) can be potentially replaced with :
test
(PET) with multiple dwell times in
You use this word too often, consider replacing it with
patients
who did not have EPS (SKI-2). The third
You use this word too often, consider replacing it with
cohort
consisted of 209
You use this word too often, consider replacing it with
samples
from the Global Fluid Study (GFS) including sequential
You use this word too often, consider replacing it with
samples
from 12 EPS & 42 matched controls
You use this word too often, consider replacing it with
patients
. MMP
You use this word too often, consider replacing it with
activity
was assessed
using the ENZchek assay system. Plasmin
You use this word too often, consider replacing it with
activity
was assessed
by using cleavage of the V0882 substrate. TIMPs, MMPs, intelectin-1, dermatopontin, and collagen (α1) I
were quantified
by commercial ELISA in PDE and
You use this word too often, consider replacing it with
plasma
You use this word too often, consider replacing it with
samples
. PDE cytology (macrophages, leukocytes, fibroblasts and mesothelial cells)
was performed
to determine if
You use this word too often, consider replacing it with
changes
in any protein could
be associated
with
You use this word too often, consider replacing it with
changes
in cell types. Clinical data
were recovered
from either the peritoneal dialysis database (PDDB) at Sheffield or the GFS archives. The analysis
was performed
using Microsoft Excel 2010 software, SPSS, and Graphpad prism (prism 5. 01 for windows). Results: Plasmin
You use this word too often, consider replacing it with
activity
in PDE
You use this word too often, consider replacing it with
samples
decreases with long duration of PD therapy. Minimal MMP
You use this word too often, consider replacing it with
activity
was found
in all PDE
You use this word too often, consider replacing it with
samples
. In the SKI-1
You use this word too often, consider replacing it with
cohort
, MMP-1, -9, & -13 were almost undetectable with
This phrase/word (depending on the context) can be potentially replaced with :
only
MMP-2 & -3 being measurable with
You use this word too often, consider replacing it with
levels
of ((mean±SD) 46±37 & 2. 1±2. 2 ng/mL
You use this word too often, consider replacing it with
respectively)
.
In contrast
TIMP-1 and TIMP-2 and to lesser extent TIMP-3 had
You use this word too often, consider replacing it with
significant
You use this word too often, consider replacing it with
levels
in PDE
You use this word too often, consider replacing it with
samples
from commencing PD (109±88, 17±12, and 0. 28±0. 33 ng/mL
You use this word too often, consider replacing it with
respectively)
. All TIMPs & MMP-2
were raised
in the single
You use this word too often, consider replacing it with
patient
who had a diagnosis of EPS. In
You use this word too often, consider replacing it with
samples
from the GFS
You use this word too often, consider replacing it with
cohort
, there was a rapid 6 fold
You use this word too often, consider replacing it with
increases
in TIMP-1 within 100 days of the diagnosis of EPS, which when normalised to TIMP-2
You use this word too often, consider replacing it with
levels
was a
This phrase/word (depending on the context) can be potentially replaced with :
good
predictor of EPS. Calculation of the
You use this word too often, consider replacing it with
plasma
to dialysate transfer rate by reference to that of circulating proteins with no peritoneal production and of known molecular weight (albumin, beta2microglobulin (B2M), transferrin, IgG, and creatinine) demonstrated that TIMPs & MMPs (
especially
TIMP-1 and MMP-2) have
You use this word too often, consider replacing it with
significant
peritoneal production.
You use this word too often, consider replacing it with
Plasma
You use this word too often, consider replacing it with
levels
for TIMP-1, -2, MMP-2, -3, and intelectin-1 (mean±SD) were 121±27, 85±16, 176±35, 11±5, and 374±136 ng/mL in healthy individuals
You use this word too often, consider replacing it with
respectively
.
You use this word too often, consider replacing it with
Plasma
You use this word too often, consider replacing it with
levels
in PD
You use this word too often, consider replacing it with
patients
for TIMP-1, -2, MMP-2, -3, and intelectin-1 (mean±SD) were 297±78, 158±33, 309±112, 42±28, and 749 ±722 ng/mL
You use this word too often, consider replacing it with
respectively
. None of the proteins identified by proteomics as predictors of EPS were able to
be validated
by ELISA.
However
TIMP-1, -2, MMP-2, intelectin-1, and collagen (α1) I in PDE
You use this word too often, consider replacing it with
samples
had
You use this word too often, consider replacing it with
significant
correlations with the loss of ultrafiltration and
thus
membrane damage. PDE cytology
This phrase/word (depending on the context) can be potentially replaced with :
showed
that peritoneal fibroblast and leukocyte numbers
You use this word too often, consider replacing it with
increase
with time on PD, while peritoneal macrophage decreases with time on PD. There were no
You use this word too often, consider replacing it with
significant
You use this word too often, consider replacing it with
changes
in mesothelial cells. Conclusions: Negligible MMP
You use this word too often, consider replacing it with
activity
in PDE
You use this word too often, consider replacing it with
samples
results from high TIMP
You use this word too often, consider replacing it with
levels
which could underlie the development of PS. The rapid
You use this word too often, consider replacing it with
increase
in TIMP-1 within 100 days of EPS development offers value as a diagnostic tool or a late biomarker.
You use this word too often, consider replacing it with
Plasma
You use this word too often, consider replacing it with
levels
of TIMP-1, 2, MMP-2, 3, and intelectin-1 are higher in
You use this word too often, consider replacing it with
patients
on PD compare to healthy individuals. The
You use this word too often, consider replacing it with
increase
in peritoneal fibroblasts may be a source of TIMP-1.
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IELTS essay Peritoneal dialysis (PD) is an important option for renal replacement therapy

Essay
  American English
1 paragraphs
707 words
6.0
Overall Band Score
Coherence and Cohesion: 5.5
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Grammatical Range: 6.5
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Task Achievement: 6.0
  • Answer all parts of the question
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    Present relevant ideas
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