Recent studies suggest that epithelial-mesenchymal transdifferentiation may be an important biological process leading to renal interstitial fibrosis. It is believed that renal tubular epithelial cells may“transdifferentiate” into fibroblasts and migrate into the interstitial space leading to fibrosis. To determine the relevance of this process in children with HIVAN, we studied renal tubular regeneration in renal sections from 25 HIV-1 infected and control children. We determined the number of cells undergoing cell death, apoptosis, proliferation, re-differentiation(positive staining for vimentin and cytokeratin) and transdifferentiation(decreased cytokeratin and increased vimentin staining) in renal tubules by light & transmission electron microscopy, immunohistochemistry and in situ hybridization studies. Kidney sections derived from children with HIVAN (n= 7), showed an increased number of renal tubular epithelial cells undergoing cell death, apoptosis, proliferation, re-differentiation and transdifferentiation. Many cells expressing α smooth muscle actin were found surrounding the tubular basement membranes. More remarkably, some urinary tubular epithelial cells (expressing positive cytokeratin, vimentin, and a smooth muscle actin staining) were cultured from the urine of HIV infected children undergoing renal injury. These cells grew on plastic, collagen I and/or matrigel coated dishes and formed monolayers,“domes” or tubule-like structures on different matrix substrata. Our findings suggest that renal epithelial cells expressing mesenchymal features may be involved in renal tubular regeneration. The expression of vimentin and/or α smooth muscle actin by these renal tubular epithelial cells may not necessary indicate that these cells are“transdifferentiating” into fibroblasts and leading to renal fibrosis. Moreover, we speculate that some mesenchymal cells may migrate through the tubular basement membranes and re-differentiate into epithelial-mesenchymal cells in the tubular lumen. The ability of the young kidney to recruit epithelial cells expressing mesenchymal features may play an important role in the pathogenesis of HIVAN.