ABSTRACT
BACKGROUND: In clinicopathological studies of cellular remodeling in the progression of diabetic nephropathy, it has not been well described whether tissue macrophage numbers and the expression of two cytoskeletal proteins--alpha-smooth muscle actin (alphaSMA) and vimentin--correlate with the disease severity. METHODS: Renal biopsy specimens from 23 patients with noninsulin-dependent diabetes mellitus (NIDDM) were examined by immunoperoxidase methods for CD68+ macrophages and alphaSMA and vimentin staining in paraffin-embedded samples. alphaSMA staining was evaluated in mesangial and interstitial myofibroblastic cells, and vimentin staining was evaluated in podocytes and mesangial and tubular cells. RESULTS: Glomerular macrophage numbers were not correlated with any clinicopathological scores. However, the interstitial macrophage score was significantly correlated with serum creatinine (sCr) and strongly correlated with the interstitial fibrosis score. Both alphaSMA and vimentin were detectable in the mesangium, without significant correlation with each other. A positive correlation was observed between mesangial alphaSMA and urinary (u-) protein levels. In contrast, an inverse correlation was observed between levels of mesangial vimentin and u-protein. Mesangial alphaSMA, but not vimentin, showed a significant correlation with glomerular sclerosis. Podocytic vimentin levels tended to decrease in patients with higher sCr levels. The severity of interstitial peritubular alphaSMA was correlated strongly with interstitial macrophage proliferation and significantly with the interstitial fibrosis score. CONCLUSIONS: The expression of mesangial alphaSMA may play a role in the progression of glomerular damage, while, on the other hand, newly acquired mesangial vimentin seems to be attenuated by heavy proteinuria. In addition, it was suggested that peritubular alphaSMA-positive myofibroblastic cells, in collaboration with interstitial macrophages, contribute to the progression of interstitial fibrosis in diabetic nephropathy.
Subject(s)
Actins/biosynthesis , Actins/metabolism , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Kidney Glomerulus/pathology , Macrophages/pathology , Vimentin/metabolism , Actins/genetics , Antigens, CD/genetics , Antigens, CD/metabolism , Antigens, Differentiation, Myelomonocytic/genetics , Antigens, Differentiation, Myelomonocytic/metabolism , Creatinine/blood , Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/genetics , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Disease Progression , Female , Fibrosis , Gene Expression Regulation , Humans , Immunohistochemistry , Kidney Glomerulus/metabolism , Macrophages/immunology , Male , Podocytes/metabolism , Podocytes/pathology , Severity of Illness Index , Vimentin/geneticsABSTRACT
We report a case of a 41-year-old woman who was diagnosed as having the syndrome of inappropriate secretion of ADH (SIADH). There was no evidence of any disorders of the central nervous system, lung diseases, or drugs causing SIADH. Positron emission tomography (PET) using (18)F-fluorodeoxyglucose (FDG) was performed and indicated a tumor of the uterine cervix. After resection of the tumor, both serum sodium level and serum osmolarity were normalized concomitantly with a decrease in serum ADH level. This is the first case report suggesting the usefulness of a FDG-PET scan to detect an occult cancer responsible for SIADH. It seems plausible that FDG-PET may be helpful in the diagnosis of other ectopic hormone-producing tumors such as ectopic ACTH-producing tumors that cause Cushing's syndrome.
