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 cellular function. 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 effusions. Peritoneal dialysis is considered as an effective mode of renal replacement therapy. 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 protein. 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 extracellular matrix. Thus, information about the localization and changes in proteins in the peritoneal membrane is provided by proteomics. 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.

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