Monocyte chemoattractant protein-1, but not RANTES plays a crucial role in the interstitial renal injury in IgA nephropathy

Background and Purpose: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, and one of the major causes of end-stage renal disease. Approximately one-third patientswith IgAN developed chronic renal failure over 30-year follow-up period. Tubulointerstitial infiltrations are found during progression of IgAN. Interstitial infiltrating immune cells could be recruited within interstitial areas by two powerful chemoattractants:monocyte chemoattractant protein-1 (MCP-1) and Regulated upon Activation Normal T-cell Expressed and Secreted (RANTES). Infiltrating macrophages are a significant source of transforming growth factor-ß1 (TGF-ß1) modulating the interstitial myofibroblasts which express -smooth muscle actin (á-SMA) activity. The present study was undertaken to evaluate the possible relationships between the immunoexpression of chemokines and their relationship with interstitial renal fibrosis in IgAN. Materials and Methods: Paraffin-embedded renal biopsy specimens of 19 patients with IgA nephropathy (diffuse mesangial proliferation, IV subclass of IgAN), and 10 normal kidneys were retrospectively studied by immunohistochemistry, using antibodies against MCP-1, RANTES, CD68, TGF-â1, á-SMA. Results: In the renal tissue in IgAN the tubulointerstitial immunoexpression of MCP-1 and RANTES was increased as compared with normal controls. The tubulointerstitial MCP-1 immunoexpression in IgAN was significantly correlated with the number of CD68+cells, immunoexpression of TGF-â1 and á-SMA in tubuli and interstitium, as well as with renal cortical volume, serum creatinine level and proteinuria. Statistical analysis did not revealed significant correlations between RANTES immunoexpression and the studied parameters. Conclusions: Based on the findings of this article we suggest that chemokine MCP-1 via TGF-â1 plays an important role in the interstitial renal fibrosis in IgA nephropathy