Randomized Controlled Trial Comparing Lactoferrin+Iron with Iron Alone for Iron Deficiency Anemia in CKD

Lactoferrin+iron significantly improved hemoglobin and iron indices versus iron alone in CKD patients with iron deficiency anemia. Lactoferrin reduced hepcidin and inflammatory markers, suggesting improved iron utilization using anti-inflammatory mechanisms. Three patients with iron deficiency anemia had elevated inflammatory markers, higher among patients with CKD on dialysis than those not on dialysis.

Lactoferrin, a multifunctional iron-binding glycoprotein with anti-inflammatory properties, is reported to be effective in anemia in pregnant women and patients with malignancy but has not been tested elaborately in CKD.

In this randomized, open-label trial, 185 patients (intention-to-treat) with iron-deficiency anemia (hemoglobin [Hb] <10 g/dl, transferrin saturation <20%) were enrolled: 90 with patients with CKD not on dialysis (CKD-ND) and 95 with dialysis-dependent CKD (patients with CKD on dialysis [CKD-5D]). Patients were randomized to receive either oral iron (30 mg/d liposomal iron) or oral iron+lactoferrin (100 mg twice daily) for 3 months. The primary outcome was change in Hb. Secondary outcomes included iron indices and inflammatory markers (C-reactive protein, IL-6, erythrocyte sedimentation rate, and hepcidin).

In the intention-to-treat analysis, lactoferrin+iron resulted in significantly greater improvements in Hb and iron parameters than iron alone in both patients with CKD-ND and those with CKD-5D. Mean Hb increased by 1.95±1.19 versus 1.33±0.86 g/dl in patients with CKD-ND and by 1.73±0.96 versus 1.11±0.93 g/dl in patients with CKD-5D receiving lactoferrin+iron and iron alone, respectively. Improvements in iron indices were also greater with add-on lactoferrin treatment. Mean difference in hepcidin levels were -20.24±15.99 versus -16.03±40.65 ng/dl in patients with CKD-ND and -15.29±8.73 versus -20.99±20.16 ng/dl in patients with CKD-5D treated with lactoferrin+iron and iron alone, respectively.

Among patients with CKD-associated anemia, adjunctive lactoferrin therapy improved Hb and iron parameters compared with oral iron alone in both non-dialysis-dependent and dialysis-dependent patients. Lactoferrin was also associated with modest improvements in inflammatory status, although effects on individual inflammatory markers were inconsistent. These findings suggest that lactoferrin may be a useful adjunct to oral iron therapy for the management of anemia in CKD, especially in resource-limited settings.

Clinical Trials Registry of India, CTRI/2020/04/024746.