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Kidney Week

Abstract: SA-PO597

Preexisting CKD Impairs Recovery from AKI in Female Rats

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Potter, Jacqui, East Tennessee State University, Johnson City, Tennessee, United States
  • Polichnowski, Aaron J., East Tennessee State University, Johnson City, Tennessee, United States
Background

We previously demonstrated that male rats with preexisting CKD exhibit impaired recovery from AKI and the subsequent development of de novo mechanisms of CKD progression. The goal of this study was to determine if impaired recovery from AKI is also observed in female rats with preexisting CKD.

Methods

We induced two levels of CKD in 10-12 week old male and female Sprague-Dawley rats by performing either 50% renal mass reduction via a right uninephrectomy (UNX, n=14, 6 females) or 75% renal mass reduction via a right UNX + surgical excision of 1/2 of the left kidney (3/4 NX, n=12, 6 females). Two weeks later, rats were subjected to 35 minute ischemia-reperfusion (IR)-induced AKI. Blood samples were obtained prior to IR and at 48 hours and 7, 14 and 28 days post IR to assess plasma creatinine (PCr). A 24-hour urine collection was performed in a subset of rats prior to IR and at 28 days post IR to assess proteinuria. At the end of the study, renal pathology and tubular vimentin expression were assessed.

Results

The severity of AKI, based on PCr levels 48 hours post AKI, was similar between UNX vs. 3/4 NX groups. The severity of AKI was lower (P<0.05) in females vs. males with 3/4 NX (1.9±0.3 vs. 3.3±0.3 mg/dl) but not significantly different between females vs. males with UNX (1.7±0.6 vs. 2.7±0.4 mg/dl). While minimal injury and vimentin expression (0.7±0.2) was observed in females with UNX, females with 3/4 NX exhibited greater (P<0.05) tubular vimentin staining (1.3±0.3), tubular injury and fibrosis 28 days post IR. Moreover, recovery of PCr over 28 days post IR was delayed in females with 3/4 NX vs. UNX. Finally, female rats with 3/4 NX developed substantial (P<0.05) increases in proteinuria 28 days post IR as compared to pre-IR levels (195±57 vs. 62±20 mg/day) while proteinuria was similar at 28 days post IR vs. pre-IR in female rats with UNX (21±4 vs. 23±5 mg/day). Males with 3/4 NX exhibited impaired recovery from AKI and the development of proteinuria 28 days post AKI as compared to males with UNX.

Conclusion

These data support previous studies documenting resistance to IR-induced AKI in female vs. male rats. However, our data indicate that preexisting CKD of greater than 50% renal mass reduction predisposes female rats to impaired recovery from AKI and the subsequent development of mechanisms of CKD progression, similar to male rats.

Funding

  • Private Foundation Support