Conversion to rapamycin immunosuppression for malignancy after kidney transplantation.

INTRODUCTION: Malignancies are a well-known complication of immunosuppressive therapy among renal transplant recipients, representing an important cause of long-term morbidity and mortality. Rapamycin has been shown to limit the proliferation of a number of malignant cell lines in vivo and in vitro. METHODS: Fifteen patients developed the following malignancies at a mean of 90.3 months (range = 10-252) after kidney transplantation: metastatic gastric cancer (n = 1), metastatic colon cancer (n = 1), bilateral nephrourothelioma (n = 1), skin cancer (n = 2), Kaposi's sarcoma (n = 2), posttransplant lymphoproliferative disorder (PTLD; n = 4), renal cell carcinoma T1 (n = 1), MALT lymphoma (n = 1), intramucous colon carcinoma (n = 1), liposarcoma of the spermatic cord (n = 1). After the diagnosis of malignancy, the patients were switched from calcineurin inhibitor-based immunosuppression to rapamycin (monotherapy, n = 3), or associated with steroids (n = 6) or with mycophenolate mofetil (n = 6). RESULTS: Both patients with metastatic cancer underwent chemotherapy but succumbed after 6 and 13 months. Two patients with PTLD who underwent chemotherapy died after 12 and 36 months. At a mean follow-up of 32.7 months (range = 7-56), the remaining 11 patients are cancer-free. Two patients lost their grafts after 24 and 36 months after the switch due to chronic rejection. Renal graft function remained stable in all other patients from diagnosis throughout follow-up. CONCLUSION: Our observations suggested that rapamycin-based immunosuppression offers the possibility for regression of nonmetastatic tumors. Nevertheless, it is difficult to assess whether tumor regression was due to rapamycin treatment or to the reduced immunosuppression.

Hemodiafiltration with post-dilution reinfusion of the regenerated ultrafiltrate: a new on-line technique.

AIMS: All convective hemodiafiltration techniques require a replacement fluid, which must have an adequate electrolytic composition and must be sterile and pyrogen-free. Using an integrated adsorption cartridge, the ultrafiltrate can be "regenerated" and used as a replacement fluid (hemo-filtrate reinfusion; HFR). The aim of this study was to evaluate whether the HFR technique as suggested in its original configuration could be improved by inverting the purification sequence (post-dilution HFR; PDHFR) in order to increase the purification efficiency of the whole system. METHODS: We performed standard HFR in 6 uremic patients during 6 months and, subsequently, during further 6 months, PDHFR. The dialytic efficacy of the two techniques and the filter blood loss were evaluated. Moreover, we studied how both techniques affected cytokine levels. RESULTS: We observed a significant increase of urea extraction and of Kt/V values in PDHFR. An equally significant improvement was observed in regard to the extraction of beta2-m and the blood loss. Furthermore, IL6 and TNFalpha decreased significantly after PDHFR treatment. CONCLUSIONS: HFR has proven to be an easy-to-perform hemodiafiltration technique, capable of resolving the typical problem of the other hemodiafiltration technique, the availability and production of a sterile and ultrapure reinfusion solution. The inversion of its configuration has allowed us to improve three aspects that have characterized, in our experience, the treatments performed in the original geometry: the removal of both urea and beta2-m, and the filter. Finally, it's notable that the decrease in cytokines levels achieved with PDHFR might attenuate the uremic micro-inflammatory state.

[Comparison between two different on-line dialytic techniques: Standard HFR vs post-dilutional HFR]. / Emodiafiltrazione con reinfusione di ultrafiltrato rigenerato in pre- e post-diluizione: due tecniche on-line a confronto.

PURPOSE: Among hemodiafiltration (HFD) techniques, hemodiafiltration reinfusion (HFR) seems unable to achieve an optimal depurative efficacy. This study aimed to evaluate whether the HFR technique as suggested in its original configuration could be improved by devising a new technique (post-dilution HFR (PDHFR)) inverting the purification sequence to increase the purification efficiency of the entire system. METHODS: We performed standard HFR in six uremic patients during 6 months and, subsequently, during a further 6 months, PDHFR was performed. The dialytic efficacy of the two techniques and the filter blood rest were evaluated. In addition, we studied the behavior of cytokines during the inverted HFR sessions. RESULTS: We observed a significant increase in urea extraction and in Kt/V. An equally significant improvement was observed with regard to beta2-microglobulin (beta2-m) extraction and blood rest. Furthermore, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) significantly decreased after inverted HFR treatment. CONCLUSIONS: The inversion of the original configuration allowed us to improve the depurative efficacy of standard HFR, increasing the removal of both urea and beta2-m, and reducing the blood rest. Finally, it was notable that the reduction in cytokine levels could attenuate the uremic microinflammatory state.