Study may identify new targets for CKD treatment

New pathways to explain the development of chronic kidney disease that could inform its treatment may have been identified in research published in Nature Medicine.

“This study is the first to look at specific cell types and how their genetic variations can lead to disease development,” Katalin Susztak, MD, PhD, co-author of the study, said in a press release.

Using a database showing how genetic variation influences messenger ribonucleic acid expression in kidney cells, Susztak and colleagues identified genes and cells associated with CKD by integrating information from CKD-related genome-wide association analysis with more specific approaches.

“In the past, many [genome-wide association analysis] GWAS efforts identified sequence variants for CKD, but the biological basis of these variants was poorly understood,” Susztak said in the release. “We need to do more with all the information we have sitting in GWAS databases to identify the genes, cells and molecular pathways responsible for CKD.”

An analysis by single-cell ribonucleic acid sequencing revealed 27 candidate genes thought to cause CKD more abundantly expressed in the proximal tubule of the kidney. Focusing on the adaptor protein disabled-2 (DAB2) in the transforming growth factor-beta (TGF-beta) pathway, researchers found it was connected to many other genes central to proper kidney function.

“We are just starting to find which molecules have gone astray to cause disease in order to develop drugs to counteract overactive molecules that cause damage to healthy tissue,” Susztak said in the release.

References:

Qiu C, et al. Nat Med. 2018;doi:10.1038/s41591-018-0194-4.

www.newswise.com/articles/view/701330/?sc=dwhr&xy=10007438

Disclosures: This research was supported by the NIH, Boehringer Ingelheim, the Eli Lilly Co. and the Juvenile Diabetes Research Foundation. Please see the full study for a list of all other authors’ relevant financial disclosures.