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Kidney Week

Abstract: FR-PO378

Energy Production System Is Suppressed in Kidneys of Low-Birth-Weight Rats, Which Develop FSGS

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Author

  • Imasawa, Toshiyuki, National Hospital Organization Chibahigashi National Hospital, Chiba, Japan
Background

Intraglomerular hypertension should be associated with the pathogenesis of FSGS lesion of low-birth-weight (LBW) related nephropathy, because LBW is significantly associated with a decreased number of nephrons. However, there is a possibility that other mechanisms participated in the pathogenesis of LBW-related nephropathy. We purposed to investigate innate factors which should be involved in the pathogenesis of LBW-related nephropathy at adulthood.

Methods

Low-birth weight rats (N = 7) were obtained by intra-peritoneal injection of dexamethasone into pregnant rats. Normal-birth weight rats (N = 7) were obtained by saline injection. At 4 weeks of age, left kidneys were removed. After that, until 9 weeks of age, rats were fed with high salt diet.

Results

At 9 weeks of age, serum creatinine levels of LBW rats were significantly higher than NBW rats (p=0.03). Furthermore, at 9-week-age, focal segmental sclerosis (FSGS) lesions were observed in 7.43% of glomeruli in LBW rats, but only 0.48% in NBW rats. On the other hand, at 4 weeks of age, there were no sclerotic lesions and any other pathological changes both in LBW rats and in NBW rats. A quantitative proteomics by using histologically normal cortexes at 4-week-age revealed marked suppression of energy metabolism in kidneys of LBW rats. For examples, 15 proteins related to TCA cycle, 15 proteins of fatty acid metabolism, 14 proteins glycolysis, and 12 proteins of mitochondrial oxidative phosphorylation were significantly suppressed in LBW rats. Bioinformatics analysis by using Ingenuity Pathway Analysis revealed RICTOR should be key regulator of these proteomic changes.

Conclusion

Kidneys in low-birth-weight rats should have suppressed energy production system before the occurrence of histological kidney damage. Not only intraglomerular hypertension, but also such innate defects of energy production, might to form FSGS lesions in LBW-related nephropathy.

Funding

  • Government Support - Non-U.S.