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Clinical and Experimental Nephrology
Published in: Clinical and Experimental Nephrology 5/2015

01-10-2015 | Original Article

Expression of age-related factors during the development of renal damage in patients with IgA nephropathy

Authors: Kyoko Yamada, Shigehiro Doi, Ayumu Nakashima, Koichiro Kawaoka, Toshinori Ueno, Toshiki Doi, Yukio Yokoyama, Koji Arihiro, Nobuoki Kohno, Takao Masaki

Published in: Clinical and Experimental Nephrology | Issue 5/2015

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Abstract

Background

Chronic kidney disease patients share clinical and pathological features with the general aging population. Increased oxidative DNA damage, accumulation of cell cycle-arrested cells and decreased Klotho expression are assumed to be age-related factors that are reportedly linked to kidney disease. This study sought to determine the association between these age-related factors and renal damage in patients with IgA nephropathy (IgAN).

Methods

We performed a cross-sectional analysis of 71 patients who were diagnosed with IgAN by renal biopsy. Expression of 8-hydroxydeoxyguanosine (8-OHdG, a marker of oxidative DNA damage), p16 (a marker of cell cycle-arrest) and Klotho (an anti-aging protein) were evaluated by immunohistochemical staining of renal biopsy samples. We correlated the changes in expression of these markers with Lee’s pathologic grades and the Oxford classification. We also investigated the independent association between these markers and interstitial fibrosis using multiple linear regression analysis.

Results

8-OHdG and p16 increased but Klotho decreased with progression of pathologic grade. Expression of 8-OHdG and p16 increased with the deterioration of mesangial hypercellularity and segmental glomerulosclerosis. In addition, p16 increased but Klotho decreased with progression of tubular atrophy/interstitial fibrosis. In univariate regression analysis, age, body mass index, systolic blood pressure, urinary protein excretion and expression of 8-OHdG, p16 and Klotho showed significant correlations with interstitial fibrosis. Multivariable regression analyses revealed that aging, increased renal expression of p16 and decreased expression of Klotho were independently correlated with interstitial fibrosis.

Conclusions

The age-related factors might play important roles in the development of IgAN.
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Metadata
Title
Expression of age-related factors during the development of renal damage in patients with IgA nephropathy
Authors
Kyoko Yamada
Shigehiro Doi
Ayumu Nakashima
Koichiro Kawaoka
Toshinori Ueno
Toshiki Doi
Yukio Yokoyama
Koji Arihiro
Nobuoki Kohno
Takao Masaki
Publication date
01-10-2015
Publisher
Springer Japan
Published in
Clinical and Experimental Nephrology / Issue 5/2015
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI
https://doi.org/10.1007/s10157-014-1070-2

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