Kidney Week

Abstract: FR-PO398

Urinary Iron and Oxidative Stress: Association with Megalin in CKD

Session Information

• CKD: Risk Factors for Incidence and Progression - I
  November 03, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

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

Shinya Nakatani,

• Nakatani, Ayumi, Osaka City University Graduate School of Medicine, Osaka, Japan

Ayumi Nakatani,

• Ishimura, Eiji, Meijibashi Hospital, Osaka, Japan

Eiji Ishimura,

• Toi, Norikazu, Osaka City University Graduate School of Medicine, Osaka, Japan

Norikazu Toi,

• Tsuda, Akihiro, Department of Nephrology, Endocrinology, Metabolism, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan

Akihiro Tsuda,

• Yamada, Shinsuke, Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan

Shinsuke Yamada,

• Mori, Katsuhito, Osaka City University Graduate School of Medicine, Osaka, Japan

Katsuhito Mori,

• Hirayama, Yoshiaki, Denka-seiken co., ltd., Gosen-shi, Japan

Yoshiaki Hirayama,

• Saito, Akihiko, Niigata University, Niigata, Japan

Akihiko Saito,

• Inaba, Masaaki, Osaka City University Graduate School of Medicine, Osaka, Japan

Masaaki Inaba,

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