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Abstract: TH-PO0055

Renal Transporter Adjustments to Maintain Homeostasis Through Lactation and Weaning

Session Information

Category: Fluid, Electrolytes, and Acid-Base Disorders

  • 1101 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • McDonough, Alicia A., University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Finch, Ariel M., University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Ye, Lorena, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
  • Ralph, Donna, University of Southern California Keck School of Medicine, Los Angeles, California, United States
  • Ray, Evan C., University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States
Background

The extreme stress of lactation requires renal transporter adjustments along the nephron to maintain effective circulating volume and prevent loss of bone minerals in the face of the substantial fluid and electrolyte delivery to mammary glands. In lactating C57B/6 dams at postpartum day 12 (P12), we observed a doubling in fractional excretion of Li and Na, and preservation of Ca, Mg, Phos, and K excretion versus nulliparous (NI) controls. PCT and TAL Na transporters (NHE3 .NaPi2, NKCC2p) decreased in abundance while TAL and DCT bone mineral-related transporters (claudin 19, calbindin, NCX, TRPV5, TRPM6) increased (Figure), indicative of redistribution of solute reabsorption downstream to the distal nephron where mineral transport is selectively up-regulated.
Hypothesis: Post-lactation renal transporter profiles return to pre-pregnancy profiles when electrolyte and bone mineral stores are restored.

Methods

At P12, pups were removed from dams, then at P18, 24 hr urine was collected in metabolic cages. On P19 (7 day post weaning) dams were terminated, kidneys collected and transporter abundance/kidney weight determined by semi-quantitative immunoblot.

Results

Dams at P19 consumed 20% more water and 50% more food than NI. Plasma electrolytes (Na, K, Li, Mg, Phos, and Ca) were normal, and urinary electrolyte excretion confirmed chow intake. Along the nephron at P19, abundance of NHE3, NaPi2, NKCC2p increased above NI and P12 levels and NCC and NKA above NI levels; abundance of Cldn19, NCX, TRPV5, TRPM6 and calbindin were maintained above NI at P12 levels (Figure).

Conclusion

At 7 days post weaning, Na and bone mineral transporters remain elevated over NI, indicative of regulatory responses to increase reabsorption in order to replenish stores despite normal plasma values and greater chow intake.

Funding

  • NIDDK Support