Injectable Cell Therapy Could Someday Treat Patients with Kidney Disease First-in-Human Study

A first-in-human study by Wake Forest Institute for Regenerative Medicine (WFIRM) researchers of an injectable cell therapy provides evidence of a potential new treatment for chronic kidney disease of unknown cause.

Chronic kidney disease of unknown cause is an aggressive disease that is often fatal, especially in resource-poor countries that have limited access to dialysis care. This new study, conducted in a small patient group in Nicaragua, demonstrates the feasibility and safety of stromal vascular fraction cell therapy.

“We found this could be a potential therapy to combat the inflammation that occurs in the diseased kidney, and it may result in improved organ function over a sustained period of time,” said Michael Carstens, MD, senior author of the paper and WFIRM faculty member. “A future randomized, controlled study of this cell therapy is needed to progress toward a treatment for this serious clinical problem.”

Chronic kidney disease begins with an acute injury to the kidney and can sometimes be related to environmental causes such as heat stress, dehydration, toxic chemicals, drugs or infectious agents. It rapidly progresses to kidney failure. No effective therapy exists to halt the structural and functional alterations in chronic kidney disease of unknown cause.

The chronic kidney disease of unknown cause affected population in Nicaragua tends to be a physical-labor, rural working-class background, according to the paper. This disease is associated with high rates of mortality in Central American countries as dialysis is often not available. Nicaragua is a small country of 6.5 million with a centralized public medical system and a limited research capability.

This is the first time that stromal vascular fraction cells have been used for the treatment of this disease, said Carstens. Injectable fat-derived mesenchymal stem cells are obtained via liposuction.

For this study, recently published in Stem Cells Translational Medicine, fat-derived cells were obtained from each of the participating 18 chronic kidney disease of unknown cause patients (stages 3-5) and were then injected directly into their kidneys via the renal artery.

Simultaneously, 12 non-treated chronic kidney disease of unknown cause patients were selected for a historical comparison, matched for age and disease stage, as a first-pass model to compare to the SVF-treated patients and to better evaluate safety and potential clinical utility. Kidney function assessment of the patients began three months prior to treatment for comparison data and continued for 36 months post procedure. Patients were evaluated with ultrasound to look for changes in renal blood flow and function.

“Our results showed that none of the patients declined in renal function,” Carstens said. “The therapy was safe and well tolerated with no serious adverse events and no procedural complications.”

Ten patients entered the study in advanced stages of chronic kidney disease of unknown cause. Of those, 3 patients in stage 5 died, two from further deterioration in their renal function. Review of these cases by a nephrologist, who was not a member of the study team, revealed no treatment related mortality.

The early disease renal pathology findings highlight the importance of a treatment that can reverse the inflammation and fibrosis, and stimulate formation of new blood vessels, according to the paper.

“This small study sample shows us that these stem cells can be safely infused into the renal artery and may have the potential to benefit patients,” said WFIRM Director Anthony Atala, MD. “These early findings provide sufficient experimental evidence to warrant a pilot study to further test this therapy for patients who suffer from kidney disease.”

Co-authors include Nelson Garcia, Sreedhar Mandayam, Biruh Workeneh, Indiana Pastora, Carlos Calderon, Kenneth A Bertram and Diego Correa.

The authors acknowledge that SVF-1 devices and enzymes for this study were donated by the GID Group. Hospital Metropolitano Vivian Pellas donated materials for catheterization.

Conflict of Interest: Carstens is a clinical consultant and has stock ownership in the GID Bio Group. Mandayam declared an advisory role with Chinook Therapeutics, received honoraria from Bayer, Otsuka, Alexion, and research funding from Horizon. Pastora declared leadership position with MD Radiology. Correa is a full-time employee of IQVIA. All of the other authors declared no potential conflicts of interest.