Title : Cyclic high hydrostatic pressure treatment to degenerate renal fibrosis in CKD
Abstract:
Today the chronic kidney diseases (CKD) or end stage renal diseases (ESRD) patients are increasing day by day. Kidney organ allograft transplant or dialysis effective treatment of choice under current circumstances. But because of the limitation of the transplant treatment and complications there is an urgent need to investigate alternative new therapeutic reliable techniques. The main cause for CKD is the presence of fibrosis in renal parenchyma producing a toxic and hostile environment i.e. prevents the regenerative process. Therefore the priority to treat CKD is to dissolve the fibrosis and restore the circulation and elasticity of the arteries which makes the environment friendly to the regeneration of the damaged tissues. Biomechanical microenvironment plays an important role in tissue development and pathogenesis. Accumulation of excessive extracellular matrix (ECM) alters tissue mechanical properties which leads to organ failure Forces potentially operate in fibrosis include hydrostatic osmotic and stretch pressure. Failure to resolve injury and restore haemostasis gives progressive fibrosis which alters the mechanical environment that is matrix deposition and stiffness. A potential regenerative approach is an in-situ repair which is an attractive strategy to tackle this problem. T he physical environment has a key role to play in regulating both cells and the organs’ ability to regenerate and repair tissues in response to injury via mechanical factors which often is overlooked in regenerative medicine. Hydrostatic pressure is the most fundamental and common mechanical stimuli in the body playing a critical role in hemostasis of the organ system. Mechanical environment that operates organ function which is a physiological system. Injury alters mechanical hemostasis and initiates reparative processes. Fibrosis represents failure to re-establishment of mechanical hemostasis and mechanical stresses that alter structural and functional properties of cells. After injury tissue rapidly changes in size, shape, composition and their mechanical characteristics. Cells are continuously exposed to a range of mechanical stresses due to the biological environment in which they reside; they play an important role in the process of constructing and modifying organs and tissues. High hydrostatic pressure has potential to disrupt structure of ECM through protein denaturation. It achieves devitalisation without damaging biomechanical properties. Intra luminal hydrostatic pressure elevation over 20-30 cms. H2O causes degenerative changes in tissues, and fibrosis. When high pressure (HP) is applied by use of a hydrostatic fluid column, a hypoxic condition is created that alters cell function, inhibits collagen matrix production and suppresses the differentiation of fibroblast to myofibroblast phenotype. Therefore, the priority to treat CKD is to therapeutically manipulate fibrosis and restore its micro vascular circulation T he fibrotic cells mechanically compressed between strong renal capsule and elevated intraluminal hydrostatic pressure by artificial obstruction created at pelvi- ureteric junction will act like closed chamber pressure. The effect of cyclic high hydrostatic pressure over renal fibrosis causes first softening of the fibrosis, seperting collagen fibres, then breaking of fibres, thinning and then eliminating the renal fibrosis. In the proposed therapy hypothesis, excessive elevation of intraluminal hydrostatic pressure will degenerate renal fibrosis and restore microcirculation functionality to eventually help to rebuild a healthy kidney from native stem cells. regeneration.
