The Race to End Kidney Dialysis

In an effort to make kidney dialysis a thing of the past, a team of Israeli researchers reports promising results in improving kidney function by removing functioning cells from the diseased kidneys of mice, rejuvenating the cells and then reimplanting them.

“The surprising finding is that when you say a kidney is critically ill or ruined, there still remains functional cells within it,” explained Prof. Benjamin Dekel, head of Pediatric Nephrology and the Pediatric Stem Cell Research Institute in Israel’s Safra Children’s Hospital at the Sheba Medical Center. “When you utilize our procedure, you can extract functional cells [from the diseased kidney], multiply them in a petri dish … and put them back.”

He said the technology has been proven to work in mice and that it has “now been commercialized to a startup company in Israel.”

Dekel said he would like to see the company start clinical trials in Israel and possibly Europe in a year or a year-and-a-half. Before they could begin in Israel, approval would have to be obtained from the Ministry of Health.

If the trial proves successful in about a year, Dekel said, the U.S. Food and Drug Administration would be approached to permit trials in the U.S., where there are a “huge number of patients.”

Shuvo Roy, a professor of bioengineering and therapeutic sciences at the University of California in San Francisco and director of The Kidney Project there, called it “laudable” that there are those working in the field of “kidney research with the goal of making dialysis a thing of the past. There is a dearth of researchers tackling the burdens of end-stage renal disease. The promising results shown in mice and the translation to humans is going to be important and the speed at which they get through human trials will be important to help advance the technology to patients.”

In his paper, Dekel wrote that “chronic kidney disease [CKD] is reaching epidemic proportions in the Western world,” and that in the United States it “affects 14 percent of the population, more than 45 million individuals. … Therapeutic options are limited to supportive care until end-stage renal disease necessitates dialysis or renal transplantation. Worldwide, 2 million people are treated with dialysis, and dialysis itself is associated with considerable morbidity and mortality. Kidney transplantation, although offering greater rehabilitation, is limited by severe organ shortages.”

Roy pointed out that “the outcomes of people on dialysis are often worse than most cancers because [dialysis] provides only some of the function of a healthy kidney. The vast majority of kidney function is not replaced, and over time the patient’s health deteriorates such that after five years, fewer than 40 percent of the patients survive.”

In Dekel’s paper, published this year in Cell Reports, he wrote that “repairing and rejuvenating or regenerating an existing diseased kidney may prevent deterioration of CKD into its terminal phases and thus reduce the need for dialysis or transplantation. A mere 5 percent change in renal function can differentiate between medical treatment in CKD stage 4 [20 percent remaining kidney function] and stage 5 CKD [less than 15 percent of remaining renal function].”

A patient is considered to have chronic kidney disease when renal function is constantly impaired, but Dekel said “that does not mean that all the [kidney] cells are dysfunctional. We can extract [healthy cells], multiply them and put them back a month later after they have been given time to grow cells outside the body. You need a lot of cells.”

If the kidney is diseased, Dekel said the rejuvenated cells might eventually need “another cell transfer. A patient might not need just one [procedure]. … I’m a believer in repeated transplant therapy.”

Because kidneys become diseased for both genetic reasons and acquired diseases, Dekel said he would prefer to conduct his trials on patients with acquired diseases such as hypertension.

“In the first trial we want to take 12 to 20 people and show that the procedure is safe and does not harm anyone,” Dekel said. “Then you look for efficacy. The nice thing about this procedure is that it does not use someone else’s cells, so at least …  it should be safer than using someone else’s cells to regenerate. … It’s a very practical, feasible approach. It is not something you would have to wait 10 years for to get the technology in line.”

Other researchers are trying to figure out a way to transplant a pig’s kidney into humans. Although pigs’ kidneys are believed to be genetically very close to those of humans, Dekel said there are “immunological hurdles because it is transplantation between species. … I want to offer a bridge for people before they need a transplant.”

He said that because dialysis is for those whose renal function has dropped to 15 percent, he would seek to help them before it gets that low. And if he could increase their renal function by 5 or 10 percent, they would not need dialysis.

“I want to be realistic,” Dekel said. “If we can delay the progression, that would be amazing. If you have a stable renal function, you can take medication and live.”

Roy cautioned that although “it’s fantastic to have [positive] results in mice, moving to humans is not a trivial task and the real breakthrough will be when we show positive results in the first human trials. Most clinical trials take longer than a year or two. The typical timeframe is five to 10 years for cell-based therapies.”

Asked if a patient with chronic kidney disease is able to maintain a stable, functioning kidney year after year, Roy replied: “It depends on the underlying disease whether it stays stable. The idea of being able to recharge the cells is attractive because it keeps patients at a 20 to 30 percent level. And we know that patients off dialysis do better than those on.”