New method for researching autosomal dominant polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic diseases in the world and affects approximately 10% of all dialysis patients. Affected patients are usually aware of their disease at a very early age (15-20 years) due to family history of the disease and the first cysts visible on ultrasound. Terminal kidney failure is then reached at an average age of 55-65 years. Aachen researchers have now succeeded in generating a model for polycystic kidney disease in cell culture. The research group from the Institute for Experimental Internal Medicine and Systems Biology, led by Prof. R. Kramann, was first able to show that a specific cell population of the human kidney is capable of forming small portions of the kidney (tubules) after isolation.

These so-called tubuloids could be modified in the next step using CRISPR/Cas9 to generate the mutations of polycystic kidney disease. „After generating mutations in PKD1 or PKD2 gene, rapid formation of cysts comparable to cysts in kidneys of patients occurred" reported Mr. Yaoxian Xu who has led the project as a PhD student for the last 5 years. „Using single cell RNA sequencing, we were able to show an amazing comparison of this cell culture system to diseased human kidneys" reports Xu. Further experiments showed that the cysts in tubuloids actually have very many characteristics of cysts in kidneys from patients and can also respond to drugs. „This work is certainly a breakthrough in the study of polycystic kidney disease and we hope that we can now use this system to develop new therapies" reports Prof. Kramann.

You can find the publication here.