Development of a cutting-edge service platform for in vivo preclinical testing of drug candidates able to treat chronic kidney disease and its associated co-morbidities.

Disorders of mineral metabolism, specifically calcium and phosphorus homeostasis, are common in patients with chronic kidney disease (CKD), diabetes and osteoporosis. CKD is a world-wide recognized public health problem affecting 8-16% of the world population. Also the prevalence of diabetes and osteoporosis is high (12.3% for diabetes and 30% for osteoporosis of all postmenopausal women) and still increasing. Essentially, these three disorders of mineral metabolism typically share interconnected features including renal failure, vascular calcification and aberrant bone metabolism. CKD represents a progressive loss of renal function over a period of months or years ultimately leading to end-stage renal disease, which inevitably requires renal replacement therapy, i.e. dialysis and kidney transplantation. Vascular calcification in the medial layer of blood vessels is a major clinical problem and the most important cause of death in CKD patients. Structures similar to bone and cartilage are detected in the calcified arterial wall thereby mimicking bone formation. In addition, the disturbed mineral metabolism in CKD patients leads to the development of renal osteodystrophy which ultimately result in a reduced bone strength and increased incidence of bone fractures. The concomitant occurrence of a disturbed bone metabolism with a pathological calcification of the vessel wall in CDK patients is referred to as "the calcification paradox", which is also observed in diabetes and osteoporosis patients. The strong increase in the number of elderly boosts the prevalence of aging-related disorders such as CKD, diabetes and osteoporosis, and herewith the interest of pharmaceutical companies in clinical as well as preclinical research on these disorders. During the last decade, the Laboratory of Pathophysiology has developed unique animal models for the in vivo investigatation of different aspects of this interconnected triad (kidney, vessels and bone) in mineral metabolism disorders. These animal models besides investigation of fundamental mechanisms underlying these pathophysiological processes also allow to intervene in these processes by candidate therapeutics. This unique combination of animal models, substantiated by fundamental pathological knowledge, resulted in a cutting edge platform for preclinical (animal model) drug testing, which successfully attracted contract research with industrial partners resulting in an income of 500k€/year during the last decade. From our unique position at the interface between academics and industry, we note that industrial interest is shifting from symptomatic treatment (hypertension or hyperphosphatemia) towards a direct interference with CKD and vessel wall calcification. To anticipate this trend and level-up the valorization potential of our current platform of animal models, this IOF-service platforms project aims to expands its portfolio and setup novel innovative animal models to guarantee a further increase in industrial revenue.

Keywords:ANIMAL MODELS

Disciplines:Vascular diseases, Kidney diseases