Acute renal failure, or ARF, is as serious as it sounds. An estimated 40% of critical care hospital admissions experience ARF. Estimates of their death rate range from 50% to 80%, complicated by the fact that patients with ARF often simultaneously suffer failure of other major organ systems.
The most serious form of ARF is caused by ischemia, or loss of blood supply to the kidneys caused by shock, blood infection or major cardiovascular surgery, particularly in such high- risk patients as those with diabetes, underlying renal disease, and the elderly. In the kidneys, such “insults” lead to destruction of kidney tubular and vascular cells, initiating a significant inflammatory response. Recovery of kidney function that is adequate for patient survival depends primarily on the protection and regeneration of destroyed and injured cells.
Yet virtually no progress has been made toward development of any highly effective ARF therapy for decades. “Basically, catastrophic loss of kidney function has remained treatment-resistant despite dialysis and intensive care. Treating patients with ARF thus presents a major clinical dilemma, particularly when severe ARF occurs with multiple organ failure,” Christof Westenfelder from the University of Utah explained. “Our laboratory has therefore been pursuing development of novel therapeutic interventions that are urgently needed to treat this common, devastating and costly human disease,” Westenfelder said.
In a new study, Westenfelder’s team reported that injecting stem cells similar to the type used in bone marrow transplants is “highly renoprotective, showing almost immediate improvement in both kidney function and degree of tissue injury, followed by accelerated regeneration and return of function,” he said.
These new results “challenge the most popular hypothesis of how stem cells work in kidney protection and repair, which holds that administered stem cells enter an injured organ where they differentiate into those cells that have been destroyed, and thus replace them both anatomically and functionally,” Westenfelder said.
Rather, the Utah team found that “administered stem cells don’t stay in the kidney that has ARF long enough to differentiate into kidney cells, but rather appear to alter the course of ARF by a number of identifiable and some still unexplored paracrine mechanisms (paracrine indicates action instigated by nearby cells).
Researchers are planning a compassionate-use study in Europe next year in patients with complicated bone marrow transplants, a setting where such stem cells already are approved for use. If successful, a compassionate-use study in patients with severe ARF and multiorgan failure will be designed, eventually leading to clinical trials.