Madhumathi Rao, MD, Assistant Professor of Medicine at Tufts Medical Center in Boston, explained that mitochondria are critical for the proliferative response of erythroid precursors in response to erythropoietin (EPO) and play an integral role in heme synthesis. Hepcidin is a regulator of iron homeostasis and is believed to play an important role in the functional iron deficiency of chronic disease anemia, including CKD.
In a study that included 154 CKD patients and 50 healthy controls (to provide baseline comparisons), Dr. Rao found that the copy number of mtDNA in peripheral blood mononuclear cells showed significant inverse relationships with glomerular filtration rate, hepcidin, and ferritin.
Hepcidin correlated inversely with EPO levels and positively with serum ferritin. In addition, a higher mtDNA copy number was a significant predictor of hemoglobin (Hb) levels, a relationship that was stronger in patients with diabetes. Plasma hepcidin levels did not show a cross-sectional association with Hb, Dr. Rao noted.
Of the 154 CKD patients, 21 had a greater than 1 g/dL decline in Hb and 12 started treatment with erythropoiesis-stimulating agents during a median follow-up of 637 days. Plasma hepcidin level was the strongest predictor of anemia progression. Patients in the third tertile of hepcidin level were 5.2 times more likely to experience progression than those in the first tertile. Dr. Rao found that mtDNA did not predict Hb decline.
“Novel mitochondrial markers and hepcidin may provide more insights into the pathophysiology of anemia in CKD,” Dr. Rao concluded. She noted that her study findings may have implications for CKD anemia therapies beyond ESA replacement. She presented the study findings here at the National Kidney Foundation’s 2010 Spring Clinical Meetings.