Abstract: SA-PO308

Sexual Dimorphism in the AKI to CKD Transition in the Rat

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 308 CKD: Mechanisms of Tubulointerstitial Fibrosis

Authors

  • Lima Posada, Ixchel Quetzaliztli, UNAM, Ciudad de México, Mexico
  • Portas cortés, Cinthya giovanna, UNAM, Ciudad de México, Mexico
  • Pérez-villalva, Rosalba, Molecular Physiology Unit, México, Mexico
  • Fontana, Francesco, Università degli studi di Modena e Reggio Emilia, Modena, Italy
  • Sanchez-Navarro, Andrea, UNAM, Ciudad de México, Mexico
  • Rodríguez Romo, Roxana, UNAM, Ciudad de México, Mexico
  • Gamba, Gerardo, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico
  • Zambrano, Elena, Instituto Nacional de Ciencias Medicas y Nutricion SZ, Mexico City, Mexico
  • Bobadilla, Norma, Molecular Physiology Unit, México, Mexico
Background

Recent epidemiological and experimental evidence has shown that after an episode of AKI, patients are at risk for developing CKD. In addition, it has been shown that the progression of chronic kidney disease is greater in men than in women before menopause, suggesting the involvement of sex hormones. This study evaluated if there is sexual dimorphism in the acute kidney injury to CKD transition, as well as the time course of the mechanisms involved in this potential dimorphic response.

Methods

Thirty nine female (F) and 39 male (M) rats were included. The rats were divided into two groups: sham operated and rats underwent 45 min bilateral renal ischemia (F+IR, and M+IR). All groups were studied and sacrificed at: 24 h, 1, 2, 4, and 4-months post-ischemia. Also, 41 oophorectomized rats were included and divided into sham or IR groups (Op and Op+IR). At the end of each experimental period, physiological, histopathological, and molecular studies were performed.

Results

We found a sexual dimorphic response in the AKI to CKD transition. After 24 h, I/R induced a similar functional and structural extent of renal injury in females and males, but female rats exhibited less oxidative stress and increased renal GSH content. After 4 months and despite similar renal injuries, the M+IR group developed CKD characterized by progressive proteinuria, renal dysfunction, tubulo-interstitial fibrosis and glomerular hypertrophy. Most of these alterations were observed since the 3rd month after IR and were associated with increased oxidative stress and a significant reduction in HIF1α, VEGF and endothelin receptor B mRNA levels since the 1st month. Interestingly, F+IR group did not develop CKD. Moreover, this group exhibited a significant increase in eNOS, TGFβ and Hif1α mRNA levels, since the 1st month after IR. Supporting this sexual dimorphism, Of+IR rats developed CKD similar to that observed in M+IR group.

Conclusion

We found a sexual dimorphic response in the AKI to CKD transition. Early antioxidant defense and higher TGFβ, HIF1α and eNOS mRNA levels were among the renoprotective mechanisms that the F+IR group demonstrated.

Funding

  • Government Support - Non-U.S.