Anemia After Kidney Transplant Worsens Outcomes

TORONTO, April 18 -- Anemia after kidney transplantation nearly doubles mortality and graft failure risk over four years, according to international researchers.

Among 938 Hungarian kidney transplant patients, anemia raised the mortality risk 69% and graft failure risk 2.5-fold, reported Istvan Mucsi, M.D., of the University of Toronto and Semmelweis University in Budapest, and colleagues, in the April issue of the American Journal of Transplantation.

The results suggested that post-renal transplant anemia should be treated according to National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for chronic kidney disease-related anemia, Dr. Mucsi said.

However, the treatment of anemia as a complication of chronic kidney disease is itself undergoing changes that suggest caution in use of erythropoiesis-stimulating agents, said Matthew R. Weir, M.D., of the University of Maryland in Baltimore, in an accompanying editorial.

Last month, the FDA issued a black box warning for erythropoiesis-stimulating agents, including darbepoetin alfa (Aranesp) and epoetin alfa (Epogen, Procrit), that pointed out aggressively raising hemoglobin to a target of 12 g/dL or higher was associated with "serious and life-threatening side-effects and/or death."

Two of the studies that sparked the warning-CREATE and CHOIR-were testing higher hemoglobin targets for chronic kidney disease patients not on dialysis.

Last week, the National Kidney Foundation updated the KDOQI guidelines to similarly recommend that the target hemoglobin "should generally be in the range of 11.0 to 12.0 g/dL" but not above 13.0 g/dL for chronic kidney disease patients.

"The recently completed CHOIR and CREATE studies, while flawed in their own right, indicated that treating could, in fact, be counterproductive," Dr. Weir said.

"The analogy with kidney transplant patients is that there may be outcome benefits or there may be risk," he said, urging patience until clinical trials find a beneficial hemoglobin target for these patients.

Recent surveys suggested the prevalence of anemia among kidney transplant patients is 30% to 40%, with 10% to 15% having severe anemia that would meet treatment guidelines for chronic kidney disease-related anemia.

Dr. Mucsi and colleagues-as part of the larger Transplantation and Quality of Life-Hungary Study--prospectively followed adult patients (mean age 49, 59% male) who had undergone a kidney transplant an average of 55 months prior to study entry (range two months to more than 10 years).

Anemia was analyzed both as defined by the American Society of Transplantation (hemoglobin under 13.0 g/dL in men and 12.0 g/dL in women) and by the KDOQI and European Best Practice guideline for treating anemia in the setting of chronic kidney disease (serum hemoglobin lower than 11.0 g/dL).

Normal hemoglobin levels for healthy adults range from 13.5 to 14.5 g/dL.

As expected, anemic patients had significantly lower estimated glomerular filtration rate levels (4320 versus 5322 mL/min/1.73 m², P

However, it was difficult to predict whether anemia would remain a predictive factor in outcomes or be buried under the significant impact of the multiple other conditions kidney transplant patients typically have, he continued.

Further study will be needed to determine if treatment could improve mortality and graft failure rates and to determine the optimal hemoglobin level for this patient population, Dr. Mucsi and colleagues noted.

For the meantime, "what we suggest is to at least consider the published guidelines that are available for chronic kidney disease patients who are not yet on dialysis, because those patients resemble kidney transplant patients at least to some extent," he concluded.

Dr. Weir agreed. The findings suggest physicians should be more mindful of anemia after kidney transplantation, he said.

"I would apply the KDOQI guidelines" with the caveats in the updated version, he added. "Maybe 11 to 12 g/dL would be a reasonable [hemoglobin] target for kidney transplant patients until we know more."