Expression of stem cell marker CD133 in fetal and adult human kidneys and pauci-immune crescentic glomerulonephritis

Background: Different cell types in the kidney, including those in tubules, glomeruli, and interstitium, have been proposed as candidate adult renal stem cells, raising controversy about the very existence of such cells. In this study, we sought to clarify the location and nature of adult renal stem cells and to address their reparative role in native kidney disease. Methods: The expression of the stem cell marker CD133 was analyzed in 31 normal fetal and adult human kidneys by immunohistochemical methods. Co expression of CD133 with Ki-67 and tubule specific markers was also examined. Seventeen cases of pauci-immune glomerulonephritis were evaluated for CD133 and Ki-67 expression, and this was correlated with the patients' renal prognosis. Results: CD133 was expressed in S-shaped bodies of fetal kidneys and co-expressed with Ki-67. It was highly expressed in mature tubules of fetal and adult kidneys without Ki-67 co-expression. CD133(+) cells were most abundant in the S3 segment of proximal tubules and co-expressed with the distal tubule marker, suggesting multipotency. Most tubular CD133(+) cells in normal adult kidneys exhibited pathologic features of acute and chronic injury. In pauci-immune glomerulonephritis, tubular CD133 and Ki-67 coexpression tended to be higher in cases where renal function recovered. Conclusion: These results suggest that adult renal stem cells reside predominantly in the S3 segment of the proximal tubule, where they remain mitotically silent under normal conditions, but can be induced by cellular injury. These results also suggest a potential role for adult renal stem cells in recovery from native human kidney disease.