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.
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Positive staining for clusterin is observed in a non-neoplastic tubule entrapped by non-reactive blastematous tumor cells. K. Renal cell carcinoma. Focal, membrane-based staining for clusterin is observed in some cells. L. Acute renal transplant rejection. Clusterin staining is observed in some tubules and tubular casts. Tubules containing positively staining casts do not necessarily show immunoreactive lining epithelium (arrow). M. Chronic renal transplant rejection. Positive clusterin staining is noted in some tubules. No interstitial staining is observed. N. Chronic renal transplant rejection. A positively staining tubule is seen next to negatively staining tubules and glomerulus. 0. Acute and chronic renal transplant rejection. Intratubular variation in clusterin staining is observed, with positive and negative epithelial cells present in this tubule. P. Acute and chronic renal transplant rejection. An epithelial cell cast positive for clusterin is present in the lumen of this tubule; the lining epithelium is moderately positive. Publication in color was made possible by educational grants from Sandoz Pharmaceuticals, Ortho Biotech, Pfizer Laboratories, and Amgen, Inc.
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.