Early diagnosis of kidney transplant rejection and cyclosporin nephrotoxicity by urine cytology

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Abstract
A total of 2000 urine samples from 53 kidney transplant recipients were studied to develop a routine method for the early diagnosis of rejection and cyclosporin (CSA) nephrotoxicity in urine. New‐Sternheimer staining and an immunocytochemical technique were used together with classical Papanicolaou staining to differentiate cells in the urine. After cell count and differentiation of second morning urine samples with New‐Sternheimer and Papanicolaou stains, immunocytochemistry was performed using antibodies against the following antigens: CD2, CD4, CD8, CD25, CD71 (transferrin receptor), HLA‐DR and cytokeratin (Lu‐5). Cell counts were obtained for the positively‐reacting cells per millilitre of urine. By New‐Sternheimer and Papanicolaou staining, CSA nephrotoxicity was characterized by the predominance of proximal tubular cells. During rejection episodes, increased numbers of mononuclear cells and renal epithelial cells were found. Immunocytochemical analysis showed a significant increase in CD2‐, CD4‐, CD8‐, CD25‐, CD71‐, and HLA‐DR‐positive epithelial cells and in the ratio HLA‐DR/cytokeratin‐positive epithelial cells in rejection. CD25‐positive cells had the highest sensitivity and specificity for the diagnosis of rejection. Our urine cytology technique proved to be a useful and non‐invasive method for the early diagnosis of rejection and CSA nephrotoxicity.