Nephrology Dialysis Transplantation, Vol 14, Issue 6 1408-1417, Copyright © 1999 by Oxford University Press
Y Ando, T Moriyama, K Oka, K Takatsuji, M Miyazaki, Y Akagi, N Kawada, Y Isaka, M Izumi, K Yokoyama, A Yamauchi, M Horio, A Ando, N Ueda, K Sobue, E Imai and M Hori
Background: With progressive renal disease, structural
derangement increasingly encompasses the tubulointersititial compartment.
Tubulointerstitial injury is a critical determinant of renal functional
reserve and prognosis in renal disease. Interstitial cells acquiring
characteristic of myofibroblasts are an important contributor to
interstitial fibrosis. Caldesmon, a calmodulin or actin binding protein, is
a molecular marker of differentiation in smooth muscle cells and has
recently been shown by us to be a good marker of mesangial cell activation
in IgA nephropathy patients. Methods: We studied
whether the expression of caldesmon in interstitium of the kidney was
enhanced in the process of glomerular disease and whether it would be a
marker of interstitial activation in specific disease states. We performed
immunohistochemical staining with anti-caldesmon antibodies in 28 biopsy
specimens from IgA nephropathy patients and analysed them quantitatively
with a computer-aided manipulator. Interstitial caldesmon expression were
compared with histological changes and clinical parameters.
Results: Caldesmon expression was enhanced where
interstitial cell infiltration and fibrosis were found. Immunoelectron
microscopy revealed that caldesmon staining in the renal interstitium was
cytoplasmic, and in the processes of myofibroblast-like cells. Caldesmon
expression was more prominent in the intense CD68 infiltrated group than
int the low positive cells infiltrated group. Patients showing high
intensity of interstitial caldesmon expression had significantly higher
urinary protein excretion than those showing low intensity of caldesmon
expression. Next, 15 patients were treated with glucocorticoid and heparin
for 4-8 weeks and re-biopsies were performed. Caldesmon expression was
reduced in concomitant with decreased interstitial cell infiltration.
Follow-up of these patients (average 24 months) revealed a significant
suppression of urinary protein excretion and significant improvement of
creatinine clearance. Conclusion: These results
suggest that the interstitial caldesmon expression is associated with the
progression of IgA nephropathy, and glucocorticoid-heparin therapy may
reverse the phenotypic change of interstitial cells during the disease
process of glomerulonephritis. Key words: caldesmon;
glucocorticoid-heparin therapy; IgA nephropathy; interstitial cell;
myofibroblast; phenotypic change
ORIGINAL ARTICLES
Enhanced interstitial expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy
Department of Internal Medicine and Therapeutics, Department of Neurochemistry and Neuropharmacology, Biomedical Research Centre; Department of Clinical Laboratory Science, Osaka University School of Medicine; School of Health ad Sport Sciences, Osaka University; Osaka Prefectural College of Nursing, Habikino, Habikinoshi, Osaka, Japan; Nara Institute of Science and Technology, Ikoma, Nara, Japan; Corresponding author at: Department of Internal Medicine and Therapeutics, Osaka University School of Medicine (A8), 2-2 Yamadaoka, Suita, Osaka 565, Japan
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