Enhanced intrarenal oxidative stress and angiotensinogen in IgA nephropathy patients

doi:10.1016/j.bbrc.2007.04.105

Biochemical and Biophysical Research Communications

Volume 358, Issue 1, 22 June 2007, Pages 156-163

https://doi.org/10.1016/j.bbrc.2007.04.105 Get rights and content

Abstract

This study was performed to determine whether immunoreactivity of intrarenal hemeoxygenase-1 and angiotensinogen are increased in IgA nephropathy (IgAN) patients. Hemeoxygenase-1 and angiotensinogen immunoreactivity were determined by immunohistochemistry robot system in renal specimens from 39 patients with IgAN. Normal portions of surgically resected kidney served as controls. IgAN patients showed moderate proteinuria (1.1 ± 0.2 g/day); however, the control group did not show any proteinuria. Immunoreactivity of intrarenal hemeoxygenase-1 and angiotensinogen in IgAN were significantly increased compared to normal kidneys (2.42 ± 0.42 vs 1.00 ± 0.26 for hemeoxygenase-1 and 4.05 ± 0.40 vs 1.00 ± 0.21 for angiotensinogen, arbitrary unit). Even though these IgAN patients did not show massive renal damage, hemeoxygenase-1 and angiotensinogen immunoreactivity were increased in these patients at this time point. These data suggest that activated intrarenal reactive oxygen species-angiotensinogen axis plays some roles in development of IgAN at the early stage and will provide supportive foundation of effectiveness of the renin-angiotensin system blockade in IgAN.

Section snippets

Materials and methods

Protocol. The experimental protocol of this clinical study was approved by the Institutional Review Board of Tulane University and Osaka General Medical Center. All samples were obtained from patients with written informed consent.

Sample collection. Thirty-nine patients (18 males and 21 females) were recruited in Osaka General Medical Center from new outpatients with occasional proteinuria who were later diagnosed as IgA nephropathy by clinical course and renal biopsy. Tissues were obtained by

Patient profiles and clinical data

Patient profiles were summarized in Table 1. As described in Table 2, IgA nephropathy patients showed higher systolic blood pressure and lower creatinine clearance compared with the control group; however, these changes were not so critical. The control group did not show any proteinuria or hematuria; however, IgA nephropathy patients also showed moderate proteinuria and hematuria. As demonstrated in Fig. 1A, immunohistochemical staining was negative for IgA in glomerulus of the control group.

Discussion

Recently clinical and experimental studies have demonstrated that the blockade of the RAS is successful in mitigation and therapy of IgA nephropathy [17], suggesting the activated RAS in the development and progression of IgA nephropathy. However, it is uncertain about detailed mechanisms of the development of IgA nephropathy or the method of radical cure is not established until now. In the present study, we provide direct evidence to demonstrate that intrarenal oxidative stress and

Acknowledgments

This study was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK072408), the National Center for Research Resources (P20RR017659), the National Heart, Lung, and Blood Institute (R01HL026371), the Health Excellence Fund from Louisiana Board of Regents, and Sankyo Co. Ltd. (Tokyo, Japan). The authors acknowledge excellent technical assistances from My-Linh Rauv, Duy V. Tran, Dale M. Seth, and Mark A. Cabrera (Tulane University).

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^☆: Portions of this study were presented in an abstract form at the 38th Annual Meeting of the American Society of Nephrology in Philadelphia, PA (J Am Soc Nephrol 16 (2005) 521A) and the 39th Annual Meeting of the American Society of Nephrology in San Diego, CA (J Am Soc Nephrol 17 (2006) 253A–254A).

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Enhanced intrarenal oxidative stress and angiotensinogen in IgA nephropathy patients☆

Abstract

Section snippets

Materials and methods

Patient profiles and clinical data

Discussion

Acknowledgments

Kidney Int.

Kidney Int.

Kidney Int.

Kidney Int.

Kidney Int.

Am. J. Kidney Dis.

Semin. Nephrol.

Biochem. Biophys. Res. Commun.

Peptides

Kidney Int.

J. Biol. Chem.

J. Biol. Chem.

Kidney Int.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Kidney Int.

Free Radic. Biol. Med.

Kidney Int.

Intercapillary deposits of IgA–IgG

J. Urol. Nephrol. (Paris)

IgA nephropathy

J. Am. Soc. Nephrol.

Frequency of renal pathology in Spain 1994–1999

Nephrol. Dial. Transplant.

Survey of the Italian registry of renal biopsies. Frequency of the renal diseases for 7 consecutive years. The Italian group of renal immunopathology

Nephrol. Dial. Transplant.

The incidence of biopsy-proven glomerulonephritis in Australia

Nephrol. Dial. Transplant.

Steroid therapy during the early stage of progressive IgA nephropathy. A 10-year follow-up study

Nephron