New mechanistic insights in genetic kidney disease

In the Netherlands, more than 6,000 people suffer from severe chronic kidney damage and require dialysis or a kidney transplant. The life expectancy of patients who need renal replacement therapy is only 5-10 years. Moreover, their quality of life is reduced. Recently acquired data indicate that genetic defects significantly contribute to their etiology, not only in children but also in adulthood. This is especially true for diseases that affect the interstitium and the tubules, which together account for up to 33% of monogenetic kidney diseases. These include ciliopathies/tubulo-interstitial diseases (e.g., nephronophthisis and uromodulin, mucin 1- and hepatocyte nuclear factor [HNF]1beta-related diseases) and tubulopathies (e.g., Bartter syndrome, cystinosis). However, many patients with suspected ciliopathy or tubulopathy remain undiagnosed. Recent genetic and technological advancements now allow, for the first time, large-scale genetic diagnostics for these patients, as well as the development of new methods for studying treatment options. With this consortium, we aimed to improve the diagnostics and quality of care for patients with ciliary and tubular disorders. We strive for a treatment that targets the individual patient and the underlying disease mechanism as effectively as possible. Therefore, we have achieved the following main objectives:
• A cohort of 150 patients has been carefully clinically examined, subjected to the new generation of genetic diagnostics, and biological material has been collected in a biobank.
• Patient-specific cell and tissue models have been developed and used for functional analyses to identify the molecular mechanisms of tubulopathies and ciliopathies.
• Pharmacological screening is being conducted using the newly developed cell models to enable individual treatment strategies for tubulopathies and ciliopathies.

As such, IMAGEN has a significant impact by improving the diagnostic pathway and treatment perspective for patients. The close collaboration with industrial partners can ensure the rapid translation of research into practice and offers new economic opportunities.