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2nd Edition of International Conference on Tissue Engineering and Regenerative Medicine

September 16-17, 2022 | Paris, France

September 16 -17, 2022 | Paris, France
TERMC 2021

Regeneration in CKD by Resolution of Renal fibrosis

Shrikant L Kulkarni, Speaker at Speaker for Tissue Engineering Conference - Shrikant L. Kulkarni
Kulkarni Clinic, India
Title : Regeneration in CKD by Resolution of Renal fibrosis

Abstract:

Chronic kidney disease is characterized by progressive loss of the renal microvasculature, which leads to local areas of hypoxia and induction of profibrotic responses, scarring and deterioration of renal function. Revascularization alone might be sufficient to restore kidney function and regenerate the structure of the diseased kidney. For revascularization to be successful, however, the underlying disease process needs to be halted or alleviated and there must remain enough surviving nephron units that can serve as a scaffold for kidney regeneration. Chronic intrarenal hypoxia and microvascular obliteration play an important role in the pathogenesis of renal scarring and loss of function, in the proposed methodology restoration of kidney structure and function is being done by arresting microvascular drop-out and restoring the interstitial capillary network could be a feasible approach to regeneration of a diseased kidney The vasculature is the core for the survival and function of every organ

In its early stages, symptoms of chronic kidney disease (CKD) are usually not apparent. Significant reduction of the kidney function is the first obvious sign of disease. CKD is a silent disease. Most CKD patients are unaware of their condition during the early stages of the disease which poses a challenge for healthcare professionals. The trouble with the diagnosis of CKD is that in most parts of the world, it is still diagnosed based on measurements of serum creatinine and corresponding calculations of eGFR. There are controversies with the current staging system, especially in the methodology to diagnose and prognosticate CKD. Fibrosis and hypoxia are major therapeutic targets for treating tubulointerstitial lesions in CKD. Protection of the tubulointerstitial vasculature theoretically should preserve blood supply and guarantee oxygenation to the corresponding compartment, which are central causes of hypoxia. Currently, no therapy exists to treat established kidney injuries. Strategies to augment human endogenous repair processes and retard associated profibrotic responses are urgently required. It would be deemed necessary to find a means to initiate an intervention well in advance of end-stage disease, when an adequate number of surviving nephrons are available.

    The self-renewal of damaged tissues is being done by the endogenous stem cells. This natural process of healing replaces young cells having strong stress tolerance for tissue survival which requires a functional vascular network at site. Self-renewal is self-organization which is the ability of a system to spontaneously arrange its element in a purposeful manner under a healthy environment without the help of external agency. because the system knows how to do its own thing.

Although fibrosis was once thought to be irreversible, there is now growing evidence suggesting that fibrosis is reversible in human fibrotic diseases under some circumstances.  Resolution can occur if the underlying etiology is eliminated. Human fibrotic diseases are often multifactorial, and eradication of the injurious stimuli may not be possible. Fibrosis is the common endpoint of chronic kidney diseases of multiple etiologies. Treating the cause of injury is perhaps the most efficacious approach to fibrosis resolution. Ideally, the rate of fibrosis resolution should be coordinated with parenchymal regeneration, since removal of the fibrotic scar without concomitant replacement with parenchyma may result in weakened tissue structure

     On resolving fibrosis, an improved blood supply recreates vivo healthy cellular microenvironment. Integrity of renal vasculature has a profound effect on renal regeneration after tissue injury mechanism that leads to new blood vessels formation, and microvascular capillaries are most important for tissue regeneration. An in-situ self-organ repair regeneration method utilizes the body's own biological resources by creating a supporting microenvironment for the endogenous stem cells to generate injured tissue structurally and functionally. The following steps are proposed in this method i) artificial hydronephrotic condition is created with help of pelvi–ureteric junction (PUJ) block ii) due to increased retrograde pressure the fibrosed renal parenchyma is dissolved iii) remove the artificial block at PUJ causing back pressure. When the fibrosis is dissolved it creates a supporting environment for endogenous stem cells to go for self-organ repair mechanisms. Theoretically the prognosis is that the endogenous stem cells niches are naturally placed between the renal capsule and the cortex and will start regeneration of new normal renal tissue. 

Biography:

Dr. Shrikant L. Kulkarni completed his M.S. (General Surgery) in 1975 from B.J.Medical College Pune, Maharashtra India. The bachelor’s degree M.B.B.S. completed from Miraj Medical College. Since 1971 he has worked at several government hospitals like the Wanless Hospital Miraj, Sangli General Hospital Sangli, Sassoon Hospital Pune and multispecialty hospitals like Ruby Hall Clinic, Pune and Jahangir Nursing Home, Pune. For the last 40 plus years he has been working at his own hospital at Chinchwad, Pune Maharashtra India.

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