A common kidney birth defect could be treatable if identified prenatally. (iStock)
Multicystic dysplastic kidney (MCDK), in which one or both kidneys fail to develop normally, is one of the most common birth defects — occurring in as many as 1 in 1,000 live births.
People can live a normal life with one kidney, but few newborns survive if fluid-filled sacs, called cysts, have replaced normal tissue in both kidneys. While the exact cause of MCDK is unknown, researchers at Vanderbilt Health have found a clue.
In the Nov. 1 issue of the Journal of Cell Biology, they report that loss of the essential regulatory protein Rac1 in mice was associated with the formation of cysts resembling those observed in children with MCDK, and that genetic mutations linked to MCDK affect the same molecular mechanism.
Furthermore, they showed that inhibition of actomyosin, the contractile protein complex which is responsible for cyst formation in the absence of Rac1, restored the maturation of affected human kidney cells grown in the laboratory and reduced early cystic changes in mice.
These findings suggest that MCDK is a potentially treatable disease if identified prenatally before cysts replace normal tissue, said the paper’s corresponding author, Fabian Bock, MD, PhD, Assistant Professor of Medicine in the Division of Nephrology and Hypertension.
For several years, Bock and his colleagues have investigated the role of Rac1 in regulating the cytoskeleton of epithelial cells in the collecting ducts and proximal tubules of the kidney.
Previously they reported that Rac1 is required for maintenance and repair of the collecting ducts, which play an important role in maintaining the body’s electrolyte and fluid balance as well as overall kidney health.
In 2025 they showed that the protein is involved in healing injuries to the proximal tubules, which reabsorb water, glucose, ions and other small molecules from the urine and thus maintain the body’s supply of these essential constituents.
In the current study, they found that, after birth, mice lacking Rac1 develop MCDK-like proximal tubular cysts.
The researchers defined the molecular mechanism by which this occurs and showed that an actomyosin inhibitor can interrupt this process. Further study will be needed, they cautioned, to determine whether sustained actomyosin inhibition can improve long-term renal function or survival.
The first author, Al Borhan Bayazid, PhD, is a postdoctoral research fellow in the Bock lab.
Other co-authors are Richard Zhang; Olga Viquez, PhD; Ryan Jannotta; Xinyu Dong; Shensen Li, MD, PhD; Matthew Tantengco; Yahu Zhang, MD; Wentian Luo, MD, PhD; Colton McAllister; Evan Krystofiak, PhD; Cord Brakebusch; Matthew Wilson, MD, PhD; Cassianne Robinson-Cohen, PhD; Andrew Terker, MD, PhD; Juan Arroyo, MD, PhD; Ambra Pozzi, PhD; and Roy Zent, MD, PhD.
The research was supported in part by National Institutes of Health grants K08DK134879, R01DK069921, R01DK088327, R01DK127589, K08DK135931, R01EB033676, DP5OD033412 and R01DK119212; by Department of Veterans Affairs Merit awards; a Southern Society for Clinical Investigation Research Scholar Award; Hakim Family Foundation Grant; ASN KidneyCure Carl W. Gottschalk Research Scholar Grant; and a KidneyCure Pre-Doctoral Fellowship.
