Tubular chimerism occurs regularly in renal allografts and is not correlated to outcome.

Recent studies have demonstrated an integration of recipient-derived progenitor cells into solid allografts with differentiation into parenchymal cells. Whether or to what extent this phenomenon influences allograft outcome has still to be elucidated. To detect epithelial chimerism tubular cells were harvested from sequential renal allograft biopsy samples by laser microdissection in 36 patients. Recipient-derived cells were detected by short-tandem repeat-based genotyping. In cases with gender-mismatched transplantation, chimerism was semiquantitatively evaluated by in situ hybridization for the Y-chromosome. Findings were correlated to different pathomechanisms of epithelial injury as well as to morphologic and clinical outcome. Epithelial chimerism was detectable as early as 8 d after transplantation and lasted for 8 yr. A total of 88% of the patients showed an epithelial chimerism; 72% had a stable chimerism in sequential biopsy samples. Evaluation of Y-chromosome by in situ hybridization revealed low percentages of chimerical tubular epithelial cells (2.4% to 6.6%). No correlation to morphology was found. Chimerism was detectable in inconspicuous protocol biopsy samples, cases of drug toxicity, and rejected allografts with and without chronic changes. No correlation was found to allograft function. Epithelial microchimerism is an early and persistent phenomenon after renal transplantation. There is no correlation to morphologic or functional outcome. Probably recipient-derived stem cells contribute in a minor fashion to tissue homeostasis, and cell turnover in renal allografts is predominantly enabled by donor cell renewal.

Incidence of polyomavirus-nephropathy in renal allografts: influence of modern immunosuppressive drugs.

BACKGROUND: In recent years an increasing number of cases with polyomavirus (PV)-nephropathy after renal transplantation were reported from several transplant centres. New, highly potent immunosuppressive drugs like tacrolimus or mycophenolate mofetil were accused as risk factors for this increase. However, data about the incidence of PV-nephropathy in correlation to different immunosuppressive therapy concepts are lacking. METHODS: All renal transplant biopsies performed at Hannover Medical School between 1999 and 2001 (n=1276) were immunohistochemically screened for the presence of PV-specific proteins. The results were correlated to the different immunosuppressive therapy protocols and patients with PV-nephropathy were compared with a matched control group. RESULTS: PV-nephropathy was found in <1% of all investigated allograft biopsies (11/1276) and in approximately 1% of all patients (7/638), respectively. All patients being immunohistochemically positive for PV-specific proteins also showed the typical morphological changes of PV-nephropathy. Four out of seven patients with PV-nephropathy were under triple immunosuppression comprising tacrolimus and mycophenolate mofetil. Under this immunosuppressive therapy protocol an eight times higher incidence and a 13 times higher risk (multivariate odds ratio 12.7) of PV-nephropathy was observed in our patients compared with the control group. CONCLUSIONS: PV-nephropathy is a rare but serious complication after renal transplantation. A small group of patients under intensive immunosuppression comprising tacrolimus in combination with mycophenolate mofetil has a significantly increased risk of acquiring this deleterious complication.