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Kidney Week

Abstract: FR-PO1038

Age-Related CKD: Roles of Advanced Glycation End Products and Insulin-Like Growth Factor Binding Protein-3

Session Information

Category: CKD (Non-Dialysis)

  • 2303 CKD (Non-Dialysis): Mechanisms

Authors

  • Liu, Shing-Hwa, National Taiwan University, Taipei, Taiwan
  • Chiang, Chih-Kang, National Taiwan University, Taipei, Taiwan
  • Chang, Ting-Yu, National Taiwan University, Taipei, Taiwan
Background

CKD is more prevalent in US adults aged 65 years or older. Advanced glycation end products (AGEs) are highly associated with diabetic nephropathy, and its levels are elevated in individuals with advancing age. A pro-apoptotic effect of insulin-like growth factor binding protein-3 (IGFBP-3) was found in diabetic nephropathy. Blood IGFBP-3 levels increase in CKD patients that is negatively correlated with eGFR. Roles of AGEs and IGFBP-3 in renal senescence and dysfunction during aging process remains unclear that's what we want to investigate.

Methods

A commercial tissue microarray for human normal kidneys from subjects with various ages was used to test the expression of Nε-(1-Carboxymethyl)-L-lysine (CML; an AGEs) and IGFBP-3. Male C57BL/6 mice with the age of 6, 19, 70 and 107 weeks were used. To determine the roles of AGEs and IGFBP-3 in aging kidney, aged mice (70-week-old) were orally administered with aminoguanidine, an inhibitor of AGEs, or injectedly administered with a neutralizing IGFBP-3 antibody.

Results

Both CML and IGFBP-3 protein expression levels in the human kidneys were significantly higher in the elderly (≥ 50 years) than in the young (p<0.05, n=24). In naturally aged mice (70- and 107-week-old), the blood renal function markers examination, Periodic acid-Schiff stain, and Masson's trichrome stain showed that there were renal dysfunction, histological changes, and collagen deposition, respectively (p<0.05, n=8). The depositions of CML/AGEs and IGFBP-3 were obviously increased in the kidneys of aged mice compared to the young controls (p<0.05, n=8). Moreover, the protein expression levels of markers for senescence and fibrosis increased in the kidneys of aged mice (p<0.05, n=8). The pathological features, increased CML and IGFBP-3 protein expression, and increased senescence and fibrosis-related markers protein expression in the kidneys of aged mice could be effectively antagonized by AGE inhibitor aminoguanidine treatment (p<0.05, n=8). The neutralizing IGFBP-3 antibody treatment could also alleviate the pathological features and fibrosis in the kidneys of aged mice (p<0.05, n=8).

Conclusion

These findings demonstrated that both AGEs and IGFBP-3 played the roles in age-related CKD. An AGEs-regulated IGFBP-3 signaling pathway may contribute to the renal dysfunction and injury during natural aging process.

Funding

  • Government Support – Non-U.S.