NDT Advance Access originally published online on July 4, 2006
Nephrology Dialysis Transplantation 2006 21(9):2472-2477; doi:10.1093/ndt/gfl260
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
Redistribution of connexin43 expression in glomerular podocytes predicts poor renal prognosis in patients with type 2 diabetes and overt nephropathy
1 Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, 2 Department of Life Science and Chemistry, Kinki University Graduate School of Agriculture, Nara, 3 Department of Nephrology, Osaka Saiseikai Nakatsu Hospital, Osaka, Japan, 4 Children's Renal Unit, University of Bristol, Bristol, UK and 5 Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Correspondence and offprint requests to: Dr Masashi Mukoyama, Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan. Email: muko{at}kuhp.kyoto-u.ac.jp
Background. Significance of podocyte injury in the progression of diabetic nephropathy is not well-understood. In this study, we examined whether alteration of gap junction protein connexin43 (Cx43) expression in podocytes is associated with the progression of overt diabetic nephropathy.
Methods. We recruited 29 type 2 diabetic patients with overt nephropathy who underwent renal biopsy. Nephrectomized kidney samples obtained from seven subjects with localized neoplasm and biopsy specimens from five patients diagnosed as minor glomerular abnormalities were used as controls. Cx43 staining on paraffin-embedded kidney sections were studied by immunohistochemistry.
Results. In controls, Cx43 was expressed at podocytes in a linear pattern along the glomerular basement membrane. In contrast, downregulation and loss of uniformly linear staining of Cx43 (Cx43 heterogeneity) in podocytes were observed in diabetic nephropathy. Cx43 intensity correlated with current renal function (R = 0.647, P < 0.005), whereas the magnitude of Cx43 heterogeneity correlated well with the degree of future decline in renal function (R = –0.705, P < 0.001).
Conclusions. Alteration of Cx43 expression in podocytes was closely associated with the progression of overt diabetic nephropathy. These results indicate that change in Cx43 expression at podocytes represents a progressive stage in overt diabetic nephropathy and that it may be a convenient way to predict future decline in renal function.
Keywords: connexin43; glomerular visceral epithelial cell; overt diabetic nephropathy; pathogenesis; podocyte; prognosis
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