Kidney disease – A seamless in vitroex vivoin vivo process

Where are we in terms of preclinical testing?

For a disease that will affect 10% of adults, chronic kidney disease (CKD) is remarkably under-diagnosed. As many as 9 out of 10 of those affected are unaware of their condition as in the early stages, there may be no obvious symptoms. In many cases CKD is diagnosed only when a routine blood or urine test is carried out. However, mostly it’s only when people start feeling sick, develop muscle cramps, high blood pressure, swollen ankles or suffer from persistent tiredness that they will visit the doctor. By then, often the disease will have reached stage 4 or 5, and is causing irreversible kidney damage.

 

One of the most difficult problems to tackle is the development of fibrosis (scarring) which is a direct consequence of the kidney’s limited capacity to regenerate after injury. Such fibrosis can develop into a life-threatening condition. At present we may be able to halt the progression of renal scarring, but that’s all. Early detection of CKD would allow improved disease management.

One thing to remember is that the aetiology of CKD is diverse. It includes immunological, mechanical, metabolic and toxic origins amongst others. To complicate the matter further it will affect three functional compartments of the kidney: the vasculature, glomerulus and tubulointerstitium . Therefore, it is extremely challenging to choose the optimal therapy. At present, renal biopsy offers one of the best methods to test for the presence of fibrosis but it requires surgical intervention, is painful, and it is very costly. A non-invasive method to detect the early incidence of such fibrosis would be lifesaving.

 

At RenaSci and Sygnature, we offer a range of preclinical translatable models that can be used to study CKD progression and preclinical drug evaluation. We have expertise in the area of diabetic kidney damage, fibrotic tissue accumulation as well as glomerular and tubular damage. We are using a wide range of plasma, urine and tissue markers such as creatinine, KIM-1 or NGAL that help to assess kidney function in preclinical models, and which readily translate to the human disease.

In general, translating animal models to the human disease isn’t simple, but at RenaSci and Sygnature we’ve created a seamless process that moves from in vitro to ex vivo to in vivo tests. Currently we focus on ex vivo tissue culture assays, such as precision-cut kidney slices that provide an excellent bridge between the in vitro tests offered by Sygnature, and RenaSci’s extensive in vivo testing capabilities in CKD. They represent a perfect approach for fast, reliable target localisation and validation in vitro settings, but on actual relevant tissue rather than a single cell line. They are not intended to replace either in vitro screens or in vivo studies: rather, they provide the link between the two. Such links will be invaluable in looking for new treatments for the many under-served patients in this therapeutic area.

RenaSci and Sygnature Discovery provide comprehensive packages of preclinical studies not only in kidney disease but in a range of other therapeutic areas. If you would like to talk with our experts about how we may be able to help your project, please get in touch using our contact form or by emailing info@renasci.co.uk

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