Stem Cells Can Help in Kidney Transplants

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By Michael Smith, North American Correspondent, MedPage TodayPublished: March 20, 2012
Reviewed by Zalman S. Agus, MD; Emeritus Professor, Perelman School of Medicine at the University of Pennsylvania.

Action Points

• In this study the use of autologous bone marrow-derived mesenchymal stem cells compared with anti-IL-2 receptor antibody induction therapy resulted in improved kidney transplant outcomes at one year.
• Note that there was a lower incidence of acute rejection, a lower risk of opportunistic infection, and better estimated renal function a year after the kidney transplant.

Stem cells, transplanted along with a kidney, can improve outcomes and reduce the need for some immunosuppressive therapy, researchers reported.
In a randomized trial, patients treated with the cells had a lower incidence of acute rejection than those given anti-interleukin 2 receptor antibody induction therapy, according to Camillo Ricordi, MD, of the University of Miami, and colleagues.
They also had a lower risk of opportunistic infection and better estimated renal function a year after the kidney transplant, Ricordi and colleagues reported in the March 21 issue of the Journal of the American Medical Association.
Antibody-based induction therapy plus calcineurin inhibitors, such as cyclosporine (Neoral) or tacrolimus (Astella), is commonly used to reduce acute rejection rates in kidney recipients, they noted.
But opportunistic infections and toxic effects of the calcineurin inhibitors are "challenging," they wrote, and novel approaches would be desirable.
Since mesenchymal stem cells have been reported to be useful in treating graft-versus-host disease, they decided to see if the approach could be used to replace antibody induction with basiliximab (Simulect), which targets the interleukin 2 receptor alpha chain on activated T lymphocytes.
At the Fuzhou General Hospital in China's Fujian province, they enrolled 159 patients with end-stage renal disease who were about to undergo a transplant from a living, related donor and randomly assigned them to three groups.
The first group of 53 patients got autologous stem cells and standard doses of calcineurin inhibitors but no interleukin 2 antibody therapy. The cell dose was between 1 and 2 million per kilogram of body weight, given at kidney reperfusion and again two weeks later.
The second 53 patients got the same therapy, except that the calcineurin doses were reduced to 80% of standard. One patient was lost to follow-up and was excluded from the analysis.
Finally, the control group of 53 patients got standard therapy with calcineurin inhibitors and interleukin 2 antibody induction, but no stem cells. Two patients were lost to follow-up.
The primary endpoint of the study was 1-year incidence of acute rejection and estimated glomerular filtration rate, while secondary measures were patient and graft survival and incidence of adverse events.
Patient and graft survival was similar in all groups.
After 6 months, 11 of the 51 controls (21.6%) had biopsy-confirmed acute rejection.
In contrast, 4 of 53 patients (7.5%) who got stem cells and standard calcineurin inhibitors and 4 of 52 patients (7.7%) in the low-dose group had acute rejection. The differences from the controls were significant at P=0.04 and P=0.046, respectively.
In both stem cell groups, estimated glomerular filtration rates recovered faster than among controls. Those getting standard-dose and low-dose calcineurin inhibitors had respective average differences from controls of 6.2 (P=0.04) and 10 (P=0.002) milliliters per minute per 1.73 meters squared.
During the 1-year follow-up, the stem cell groups combined had a decreased risk of opportunistic infections, compared with controls. The hazard ratio was 0.42, with a 95% confidence interval from 0.20 to 0.85, which was significant at P=0.02.
Although the stem cells appeared safe, the researchers wrote, "extended monitoring of study participants will allow assessment of the long-term effects of autologous MSCs on renal allograft function, survival, and safety."

The study had support from the Key Science Research Project and the Key Laboratory, both of Fujian Province, China.
The researchers did not make any disclosures, the journal said.

Primary source: Journal of the American Medical Society
Source reference:
Tan J, et al "Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial" JAMA 2012; 307(11): 1169-1177.