Aims.To provide the first single-center study of a Czech renal transplant program that compares skin cancer risk estimates to the general population.Methods. We studied a total of 603 patients undergoing renal transplantation at the University Hospital Olomouc Transplant Center between January 1984 and December 2009. The mean time of follow-up was 5.5 years. Three patients were excluded for skin cancer diagnosis before transplant. The cohort was linked with the National Cancer Registry of the Czech Republic. For non-melanoma skin cancer (NMSC), the observed number of cancers were compared to the expected numbers of NMSC based on national cancer incidence rates stratified by age. The standartized incidence ratio (SIR) was calculated as observed-to-expected ratios.Results. We found a total of 127 cases of skin cancers in 55 patients. 52/55 (94.5%) were patients with non-melanoma skin cancers, 2/55 (3.6%) patients had malignant melanoma, and we uncovered one case of merkel cell carcinoma of the skin (1.8%). There were no cases of Kaposi's sarcoma, cutaneous lymphoma or malignant fibrous histiocytoma. For NMSC, the overall SIR was 7.39 (95% confidence interval 5.52-9.70). Thus, skin cancer was the most common malignant condition, representing 64.1% of all malignant tumours detected in study population.Conclusion. We confirmed that skin cancer is a major complication in renal transplant recipients. Therefore it is important to increase the intensity of surveillence for these lesions in transplant patients.
Summary
The 6 month prospective, randomized study compared the steroid‐sparing potential of two tacrolimus‐based regimens after renal transplantation. A total of 489 patients were randomized (1:1) to receive tacrolimus/mycophenolate mofetil (MMF)/steroids (n = 243; group Tac/MMF/S) or tacrolimus/azathioprine/steroids (n = 246; group Tac/Aza/S). At 3 months, steroids were tapered off in 267 (54.6%) patients free from steroid‐resistant acute rejection and with serum creatinine concentrations <160 μmol/l. The incidence of biopsy‐confirmed acute rejection at month 3 was lower in group Tac/MMF/S compared with group Tac/Aza/S (18.1% vs. 26.0%,P = 0.035). Moreover, more patients in the Tac/MMF/S group met the criteria for steroid withdrawal than in the Tac/Aza/S group (60.5% vs. 48.8%; P < 0.01). The incidence of acute rejection during months 4–6 was low in all groups, both for patients on steroid‐free dual therapy (Tac/MMF: 2.7%, Tac/Aza: 0.8%) and for patients who continued steroid maintenance therapy (Tac/MMF/S: 3.5%, Tac/Aza/S: 7.1%). Moreover, kidney function was well preserved in steroid‐free patients with month 6 median serum creatinine levels of 119.5 μmol/l (Tac/MMF), and 115.1 μmol/l (Tac/Aza). For patients who continued to receive steroids, month 6 median creatinine levels were 130.5 μmol/l (Tac/MMF/S) and 132.8 μmol/l (Tac/Aza/S). The criteria for the selection of patients to discontinue steroids were adequate. Both tacrolimus‐based regimens allowed the safe discontinuation of steroids in low‐risk patients at month 3. The Tac/MMF combination was superior in the prevention of acute rejections and more patients met the chosen criteria for steroid withdrawal.
Background. The introduction of the calcineurin inhibitors (CI) cyclosporine and tacrolimus into immunosuppressive protocols initiated a new era in organ transplantation with excellent short-term graft survival. Nevertheless, the chronic nephrotoxicity of these drugs represents a significant adverse factor limiting their long-term use. Patients treated with a CI can be at risk for developing renal failure and this problem is especially pronounced in patients after renal transplantation.Methods and Results. In a review paper we summarize the clinical aspects, histological manifestations and pitfalls of diagnostics of acute and chronic CI nephrotoxicity in patients after kidney transplantation. We look in detail at the disputed relationship between blood concentrations of cyclosporine and tacrolimus and histological manifestation of toxicity and summarize data showing that for toxic effects, local renal exposure to CI and their metabolites can play a more significant role than systemic exposure. We also include recent views on the pathophysiologic and molecular mechanisms underlying these changes; factors influencing local susceptibility to CI nephrotoxicity are discussed, including variability of expression and activity of P-glycoprotein and cytochrome P450. Last but not least we summarize our own experience with clinically manifest and subclinical forms of nephrotoxicity and their impact on the progression of chronic graft changes.Conclusions. Owing to their unique effects, CI remain the cornerstone of most immunosuppressive protocols for renal transplantation. Together with optimization of local kidney exposure to CI and their metabolites, efforts to reduce systemic levels as much as possible are the most important preventive measure for reducing toxic renal graft damage.
Backround: Posttransplant lymphoproliferative disorder (PTLD) is increasingly recognized as a serious complication of solid organ transplantation in both children and adults. Factors associated with increased risk of PTLD include mismatch of recipient and donor EBV serologic status (seronegative recipient with seropositive donor), and intensive drug-induced immunosuppression.Methods and results: We searched MEDLINE for articles published since 1970 to January 2009. Search terms included posttransplant lymphoproliferative disorder, immunosuppression, posttransplant malignancy, treatment, antiviral agents, rituximab, interferon alpha, chemotherapy, radiation, surgery. Studies in English of adult and pediatric populations after solid organ transplantation were selected and analyzed.Conclusion: Screening of patients at risk and balancing the intensity of immunosuppression against the risk of allograft rejection could reduce the risk of developing PTLD. In patients who develop PTLD, the severity and extent of disease should be examined and an individualized treatment plan including immunosuppression reduction and other agents should accordingly be chosen.
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