Iron Deficiency and Renal Development in the Newborn Rat

Abstract

Iron is essential for fetal organ development, but the effect of isolated iron deficiency on nephrogenesis is unknown. Human premature infants are at risk for disrupted nephrogenesis because glomerular development is incomplete until 36-wk gestation. We modeled the effects of iron on postnatal glomerulogenesis in four groups of immature rats from P4 to P12: dam fed controls (DF), dam fed with sham gastrostomy surgery (DF + SS), iron-deficiency anemia (IDA), fed iron-deficient formula through gastrostomy apart from the dam, and IDA plus simultaneous enteral iron rescue (IDA+Fe). Hematocrit, plasma ferritin, and body and kidney tissue iron contents were measured. Tissue was examined. Rats grew similarly, but IDA rats exhibited lower hematocrit, plasma ferritin, and body and kidney iron contents than DF, DF + SS, or IDA + Fe. IDA exhibited 1.7 fewer radial glomerular counts (RGCs), 26% reduced glomerular density, and 29% less planar glomerular surface area than DF, with partial improvement in IDA + Fe. Compared with DF or DF + SS, we observed elevated plasma CRP levels and tubulointerstitial fibrosis in the IDA and IDA + Fe groups. IDA reduced glomerular density, glomerular surface area, and promoted fibrosis. Iron substantially rescued renal growth and development, supporting the critical role of iron in late nephrogenesis.