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Kidney Week

Abstract: FR-PO1006

N-Acetylcysteine Ameliorates Hematuria-Associated Tubulointerstitial Injury in 5/6 Nephrectomy Mice

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Brodsky, Sergey V., The Ohio State University, Columbus, Ohio, United States
  • Medipally, Ajay Kumar, The Ohio State University, Columbus, Ohio, United States
  • Xiao, Min, The Ohio State University, Columbus, Ohio, United States
  • Biederman, Laura, The Ohio State University, Columbus, Ohio, United States
  • Dasgupta, Alana, The Ohio State University, Columbus, Ohio, United States
  • Mikhalina, Galina, Rochester Regional Health, Rochester, New York, United States
  • Satoskar, Anjali A., The Ohio State University, Columbus, Ohio, United States
Background

Chronic kidney disease (CKD) is characterized by increased interstitial fibrosis and tubular atrophy (IFTA) in the kidney. Chronic hematuria is a hallmark of several human kidney diseases and often is seen in patients on anticoagulation therapy. We had previously demonstrated that chronic hematuria associated with warfarin increases IFTA in 5/6 nephrectomy (5/6NE) rats, and such treatment increases reactive oxygen species (ROS) in the kidney.
The goal of this study was to evaluate the effects of the antioxidant N-acetylcysteine (NAC) on the progression of IFTA in 5/6NE mice.

Methods

5/6NE C57BL/6 and 5/6NE 129S1/SvImJ mice were treated with warfarin alone or with warfarin and NAC for 23 weeks. Serum creatinine SCr), hematuria, blood pressure (BP), and ROSs in the kidney were measured; kidney morphology was also evaluated.
Warfarin doses were titrated to achieve prothrombin time (PT) increase to the levels seen with therapeutic human doses.

Results

Warfarin treatment resulted in an increased SCr, systolic BP, hematuria (Figure 1), and ROS in the kidney in both mouse strains. IFTA was increased as compared with control 5/6NE mice, and this increase in IFTA was more prominent in 129S1/SvImJ than in C57BL/6 mice. NAC ameliorated the warfarin-associated increase in SCr and BP but not hematuria. IFTA and ROS in the kidney were reduced in mice treated with NAC and warfarin as compared to mice treated with warfarin alone.

Conclusion

NAC mitigates the increase in SCr and IFTA in mice with chronic hematuria by reducing oxidative stress in the kidney. This data open novel possibilities for treatments in CKD patients.

Figure 1. Changes in serum creatinine and hematuria in mice treated with NAC and warfarin.

Funding

  • NIDDK Support