Enhanced interstitial expression of caldesmon in IgA nephropathy and its suppression by glucocorticoid-heparin therapy.

reduced in concomitant with decreased interstitial cell infiltration. Follow-up of these patients (average 24 Background. With progressive renal disease, structural derangement increasingly encompasses the tubulointer- months) revealed a significant suppression of urinary protein excretion and significant improvement of creatstitial compartment. Tubulointerstitial injury is a critical determinant of renal functional reserve and inine clearance. Conclusion. These results suggest that the interstitial prognosis in renal disease. Interstitial cells acquiring characteristic of myofibroblasts are an important con- caldesmon expression is associated with the progression of IgA nephropathy, and glucocorticoid—heparin tributor to interstitial fibrosis. Caldesmon, a calmodulin or actin binding protein, is a molecular marker of therapy may reverse the phenotypic change of interstitial cells during the disease process of glomdiVerentiation in smooth muscle cells and has recently been shown by us to be a good marker of mesangial erulonephritis. cell activation in IgA nephropathy patients. Methods. We studied whether the expression of caldes- Key words: caldesmon; glucocorticoid—heparin mon in interstitium of the kidney was enhanced in the therapy; IgA nephropathy; interstitial cell; myofibrobprocess of glomerular disease and whether it would be last; phenotypic change a marker of interstitial activation in specific disease states. We performed immunohistochemical staining with anti-caldesmon antibodies in 38 biopsy specimens Introduction from IgA nephropathy patients and analysed them quantitatively with a computer-aided manipulator. In the progression of renal disease, interstitial fibrosis Interstitial caldesmon expression were compared with is found regardless of whether the primary injury is of histological changes and clinical parameters. glomerular or tubulointerstitial origin. The decline in Results. Caldesmon expression was enhanced where renal function has been shown to correlate better with interstitial cell infiltration and fibrosis were found. tubulointerstitial changes than with glomerular damImmunoelectron microscopy revealed that caldesmon age per se. [1,2]. Thus, tubulointerstitial changes are staining in the renal interstitium was cytoplasmic, and thought to be critical determinant of renal functional in the processes of myofibroblast-like cells. Caldesmon reserve and prognosis in glomerular disease. There is expression was more prominent in the intense CD68 increasing evidence that interstitial cells are activated infiltrated group than in the low positive cells infiltrated during initial injury and undergo a variety of phenogroup. Patients showing high intensity of interstitial typic changes as characterized by alteration of cell caldesmon expression had significantly higher urinary morphology, acquisition of proliferative phenotype, an protein excretion than those showing low intensity of increased synthesis of extracellular matrix and an caldesmon expression. Next, 15 patients were treated enhanced secretion of growth factors such as plateletwith glucocorticoid and heparin for 4‐8 weeks and derived growth factor and transforming growth factorre-biopsies were performed. Caldesmon expression was b [3]. Recent findings demonstrated that the enhanced