ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO398

Urinary Iron and Oxidative Stress: Association with Megalin in CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Nakatani, Shinya, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Nakatani, Ayumi, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Ishimura, Eiji, Meijibashi Hospital, Osaka, Japan
  • Toi, Norikazu, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Tsuda, Akihiro, Department of Nephrology, Endocrinology, Metabolism, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Yamada, Shinsuke, Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Mori, Katsuhito, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Hirayama, Yoshiaki, Denka-seiken co., ltd., Gosen-shi, Japan
  • Saito, Akihiko, Niigata University, Niigata, Japan
  • Inaba, Masaaki, Osaka City University Graduate School of Medicine, Osaka, Japan
Background

Megalin mediates the uptake of glomerular-filtered iron in the proximal tubules. Sandwich enzyme-linked immunosorbent assays have been developed to measure urinary ectodomain (A-megalin) and full-length (C-megalin) forms of megalin using monoclonal antibodies against the amino- and carboxyl-terminal of megalin, respectively. Urinary C-megalin excretion is increased via exocytosis in association with megalin-mediated metabolic load to the endo-lysosomal systems in the proximal tubules of residual nephrons. Thus, the present study investigated the association between urinary iron and megalin in chronic kidney disease (CKD) patients, and the possible harmful effect of iron in renal tubules.

Methods

The urinary levels of iron, megalin, and other markers were measured in 63 CKD patients, and their associations were evaluated by Pearson’s and Spearman’s analyses followed by multiple regression analyses.

Results

. Urinary iron was 109 [69.3–166] μg/g Cr. Urinary total protein correlated significantly (r = 0.528, p < 0.001) with urinary C-megalin, but not with A-megalin. Although both urinary C-megalin and urinary total protein correlated with urinary iron (C-megalin: r = 0.574, p < 0.001; total protein: r = 0.500, p < 0.001, respectively), urinary C-megalin alone emerged as an independent factor associated positively with urinary iron (β = 0.520, p < 0.001) (R2 = 0.75, p < 0.001). Furthermore, urinary iron was associated significantly and positively with urinary 8-hydroxydeoxyguanosine, an oxidative stress marker, whereas none of the tubular markers, including urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase, were associated with urinary 8-hydroxydeoxyguanosine

Conclusion

In conclusion, renal iron handling may be associated with oxidative stress in renal tubules and megalin-mediated endo-lysosomal metabolic load in the proximal tubules of residual nephrons.

Funding

  • Private Foundation Support