In a world first, an international team led by scientists from Duke-NUS has shown that restoring damaged kidneys to full health may soon be a possibility. Using an antibody therapy, the scientists were able to block the uptake of signals that prevented kidney cells from repairing themselves. While the discovery was confirmed in preclinical models and human cells, the same antibody is about to enter phase I safety trials for a similar application in the lungs.

“Kidney failure is a global epidemic,” said Assistant Professor Anissa Widjaja, a molecular biologist with Duke-NUS’ Cardiovascular & Metabolic Disorders Programme, who led the study. “Closer to home, Singapore ranks first in the world for diabetes-induced kidney failure and fourth in terms of kidney failure prevalence.”

Widjaja, who worked with colleagues Professors Stuart Cook and Thomas Coffman as well as collaborators in Germany, identified the crucial role played by the immune-regulating protein interleukin-11 (IL-11) in triggering a cascade of signals when the kidney is injured. These signals, in turn, led to inflammation, scarring and damage in the kidney.

“We found that IL-11 is detrimental to kidney function and triggers the development of chronic kidney disease,” said Cook, who is also Tanoto Foundation Professor of Cardiovascular Medicine at the SingHealth Duke-NUS Academic Medical Centre, and a senior consultant with the National Heart Centre Singapore. “We also showed that anti-IL11 therapy can treat kidney failure, reverse established chronic kidney disease, and restore kidney function by promoting regeneration while being safe for long-term use.”

Anissa Widjaja (left) and Stuart Cook (right) led this work which will bring hope to millions of patients worldwide

Their preclinical studies, published in Nature Communications, show that administering an antibody that binds to IL-11 can turn off this process, reversing the scarring and dampening inflammation while encouraging proliferation of renal tubular cells, resulting in regeneration of the injured kidney and a restoration of renal function.

“By boosting the kidney’s intrinsic capability to regenerate, the team has shown that we can restore function to a damaged kidney,” said Coffman, Dean of Duke-NUS who is also the principal investigator of the Diabetes Study in Nephropathy and other Microvascular Complications (DYNAMO), a large collaborative study that aims to find new solutions for the prevention and treatment of diabetic kidney disease.

“By boosting the kidney’s intrinsic capability to regenerate, the team has shown that we can restore function to a damaged kidney,” said Coffman, Dean of Duke-NUS who is also the principal investigator of the Diabetes Study in Nephropathy and other Microvascular Complications (DYNAMO), a large collaborative study that aims to find new solutions for the prevention and treatment of diabetic kidney disease.

“This discovery could be a real game-changer in the treatment of chronic kidney disease—which is a major public health concern in Singapore and globally—bringing us one step closer to delivering the benefits promised by regenerative medicine.”

Prof Thomas Coffman