Preliminary Studies on Proteomics
and Peritoneal Dialysis
Reference: Brewis IA, Topley N.
Proteomics and peritoneal dialysis:
Early days but clear potential. Nephrol
Dial Transplant. 2010;25:1749–1753.
Global Analysis of Proteomics
• Proteomics and its application have lead the post-genomic
technologies, as it has helped in the understanding the central role
of proteins and protein–protein interactions in the entire aspects of
• Quantification and global identifications of proteins, not only help
in understanding a diseased or healthy individual but also lead to
the discovery of biomarkers.
• Biomarker discovery has profuse scientific evidence from
proteomics and suggests that most of the diseases are caused due
to changes in certain proteins in the plasma.
• The clinical specimen or biological fluids probably contain a protein
profile, which indicates diseases in that organ system like studies on
urine can be related to kidney and bladder diseases, cerebrospinal
fluid for neurological conditions.
Proteomics to Study Peritoneal Dialysis
• Paucity of data is the main reason for few studies on
• Peritoneal dialysis is considered as an effective mode of renal
• This offers analysis of peritoneal dialysis effluents (PDE) from
all types of patients and can also provide critical information
about PD exclusively, along with general information about
the peritoneal environment. A study from this paper was the
first to show the differences between diabetic PDE and
normal peritoneal fluid.
• The methods involved two dimensional electrophoresis (2DE);
a gel-based approach for the analysis of proteins and was
later confirmed by western blotting.
• Inclusions like vitamin D-binding protein, haptoglobin and α2-
macroglobulin at raised levels, and complement component
C4A and immunoglobulin κ at lower levels were considered
and confirmed through western blotting.
• Change in the permeability of the peritoneal membrane,
caused by the loss of vitamin binding protein, haptoglobin and
α2-macroglobulin leads to loss and leakage of medium-sized
• This paper also proposes that peritoneal membrane scleroses
are caused due to certain mechanisms.
• Differentiation and identification of proteins in diabetic PDE
and normal fluid will surely help in further studies.
• Another sophisticated methodology, gel electrophoresis then
liquid chromatography-mass spectrometry (GeLC-MS) was
considered with nine pediatric PD patients for the
identification of 189 PDE proteins.
• Different levels of C4A and immunoglobulin κ were shown in
20 chronic PD patients with altering transport rates.
• Identification of 5 proteins was done at different levels among
the transport groups after 2DE. Increased levels of C4A and
immunoglobulin κ in higher transport vs. lower transport
patients were confirmed, in particular by further validation
set of 24 patients by ELISA.
• This further emphasizes that proteomics can be used in
comparing differences in different subgroups.
• Analysis revealed that these proteins were derived from the
extracellur matrix, suggesting retention of PD fluid within the
• Thus, information about the localization and changes in
proteins in the peritoneal membrane is provided by
• Proteomics technology has lead to the discovery of unknown
proteins like gelsolin and intelectin. Gelsolin plays a role in
protecting mesothelial cell damage against infection and is
used as a marker in sepsis.
• Intelectin has a defensive role against permeable intestinal
bacteria and parasites in the peritoneal cavity.
Time Now for more Extended Studies
• Till date only initial studies have been carried out, and prospective studies
involving greater number of patients is required for more information
about the changes in the peritoneal dialysate proteins that are associated
with particular phenotypes like nutritional status, risk of peritoneal
infection, membrane function, residual renal function and fibrosis.
• This information can be used for further advanced analysis.
• Less number of proteins is identified till date with majority of the proteins
yet to be discovered.
• With the present expensive and technically challenging ways, efforts are
emphasized on identification of novel proteins to enable new hypothesis
to be formed or identification of novel prospective biomarkers, through a
range of workflow choices.
• In addition, proteomics technology has adapted 2DE-based difference gel
electrophoresis (DIGE) or Lcbased MS labeling workflows, such as isobaric
tags for relative and absolute quantification (iTRAQ) as gold standards for
relative protein quantification.
The Achilles’ Heel of Proteomics
• Analysis of biological fluids is not an easy process and the potential
of biological marker discovery is limited, as it is a challenging
process and this has lead to the lowest discovery.
• A difference of 10 orders of magnitude is observed among largely
and the least abundant proteins in the biological fluids.
• The available analytical technologies have 2–4 orders of magnitude
dynamic range for protein detection.
• This suggests that there is a deficit and hence not all proteins can
be discovered using these methods.
• Still these methods have importance as they can be used in the
identification of proteins, which had not been previously identified.
• Although certain sample fractionation approaches can be used to
improve specificity, hypothetical changes are essential in
proteomics technology in the discovery of all proteins.
Looking into the Future
• Preliminary studies on PDE proteomics promotes understanding PD.
• Function of the kidney, pathological damage of the peritoneum can
be identified without invasive techniques.
• Discovery of biomarkers helps in measuring peritoneal damage and
changes in transport through noninvasive methods.
• In addition to this, the effect of different dialysis fluids and
prolonged PD period on protein profiles might also be investigated
to offer better understanding of the pathological processes.
• Advanced studies are guaranteed in this field for better diagnosis,
prognosis and therapeutic monitoring of pathological processes.
• Proteomics is a podium in providing assistance in both
understanding and utilization of PD.
in Anemia Management