Use of bioartificial kidney may improve survival, accelerate recovery of kidney function in patients with acute renal failure, researchers report

Treatment with a bioartificial kidney may improve survival and accelerate recovery of kidney function in patients with acute renal failure, according to findings from a recent study.

Researchers conducted a Phase II, prospective, open-label clinical trial in which 58 patients who required continuous renal replacement therapy (CRRT) to treat ARF secondary to acute tubular necrosis in an intensive care unit were randomized to receive continuous venovenous hemofiltration (CVVH) plus...

Treatment with a bioartificial kidney may improve survival and accelerate recovery of kidney function in patients with acute renal failure, according to findings from a recent study.

Researchers conducted a Phase II, prospective, open-label clinical trial in which 58 patients who required continuous renal replacement therapy (CRRT) to treat ARF secondary to acute tubular necrosis in an intensive care unit were randomized to receive continuous venovenous hemofiltration (CVVH) plus a renal tubule assist device (RAD; n=40) or CRRT alone (n=18) for 72 hours. The primary efficacy endpoint was all-cause mortality at 28 days.

Results indicated that, at the end of the study period, 13 patients (33%) in the RAD group had died compared with 11 (61%) in the control group (P=.082). This absolute reduction in mortality among patients in the RAD group was maintained at 90 days and 180 days, and was statistically significant at 180 days (P=.034).

Overall, the risk of death among patients in the RAD group was significantly lower than among patients in the control group (HR, 0.481; 95% CI, 0.23-0.99).

Additionally, by day 28, 21 patients (53%) in the RAD group recovered renal function compared with 5 patients (28%) in the control group, 10 patients (25%) in the RAD group died before recovery compared with 9 (50%) in the control group, and 8 (20%) in the RAD group remained on renal support compared with 4 (22%) in the control group.

These improvements in RAD-managed patients were maintained in subgroup analysis; specifically, the mortality rates were 60% in the RAD group compared with 100% in the control group among the subset of patients with 5 or more organ failures, and 34% in the RAD group compared with 67% in the control group among the subset of patients with sepsis.

Serious adverse events were reported in 68% of patients in the RAD group and 89% of patients in the control group. The events were typical of a seriously ill patient population in the ICU with ARF and receiving dialysis therapy, the authors noted.

"Despite the critical nature and life-threatening illnesses of the patients enrolled in this clinical study, the addition of renal tubule cell therapy to CVVH resulted in a substantive clinical impact on survival compared with a conventional CRRT group," the authors concluded. (Tumlin J, et al. J Am Soc Nephrol 2008;19:1034-1040.)

In an accompanying editorial, Drs. Glenn Chertow of Stanford University School of Medicine and Sushrut Waikar of Brigham and Women's Hospital commended Tumlin et al. for their research, which "represents a landmark event in the history of nephrology."

However, they noted that this trial suffered from numerous flaws in its design, including being "hopelessly underpowered" because of its small sample size, as well as having no documentation as to why all but 10 patients randomized to the RAD group failed to complete the planned 72 hours of therapy, a statistically nonsignificant primary outcome, no consideration for the statistical implications of multiple outcome comparisons, and little documentation of the expected effect size to guide subsequent trials.

"Despite these limitations, the investigators should be commended for having extraordinary vision, courage, and creativity to invent and legitimately test a bioartificial renal devices," they concluded. (J Am Soc Nephrol 2008;19:839-840.)

This information concerns a use that has not been approved by the Food and Drug Administration.