Clusterin, a glycoprotein with potent cohesive properties, is induced in a wide variety of acute and chronic experimental renal diseases. The purpose of this study was to examine clusterin expression in human renal diseases. Clusterin immunostaining was examined in nephrectomy specimens from patients with autosomal-dominant polycystic kidney disease (N = 5), autosomal- recessive polycystic kidney disease (N = 3), multilocular cyst of the kidney (N = 2), renal hypoplasia/dysplasia (N = 7), Wilms' tumor (nephroplastoma) (N = 6), renal cell carcinoma (N = 9), and acute and/or chronic renal transplant rejection (N = 15). No clusterin staining was detected in normal renal tissue distant from renal cell carcinomas. Increased expression of clusterin was found in epithelial cells lining cysts in all of the cystic disorders studied. Clusterin expression was found in some immature tubules in hypoplastic/dysplastic kidneys and in tubules of rejected renal allografts, but was not a prominent finding in renal neoplasms, although some renal cell carcinomas expressed clusterin in a focal manner. Common features of clusterin induction included exclusively epithelial production of clusterin in cysts, immature nephrons, and injured tubules, heterogeneity of clusterin expression, with only some tubules and/or cysts in a given area staining for clusterin, and uniform clusterin staining of epithelial cells in a given tubule or cyst in most cases. Based on its cohesive properties, we speculate clusterin functions to maintain cell-cell and cell-substratum interactions which become perturbed in the setting of renal injury and cystic diseases.
Bibliographical noteFunding Information:
This work was supported by US Public Health Service Grant R29 DK43075 (M.E.R.) and a grant from the Minnesota Medical Founda- tion. The authors are grateful to Sandoz Pharmaceuticals, Ortho Biotech, Pfizer Laboratories, and Amgen, Inc. for publication of the figures in color, Jeffrey Dvergsten was supported by an American Heart Association Medical Student Research Fellowship. Dr. Correa-Rotter was a recipient of Juvenile Diabetes Foundation International Postdoc-toral Research Fellowship, and was also partially supported by the "Instituto Nacional de la Nutrición Salvador Zubirán", Mexico City, Mexico. We thank David Chmielewski for his technical assistance and Brendan Murphy for the clusterin monoclonal antibody.