Long-term belatacept exposure maintains efficacy and safety at 5 years: results from the long-term extension of the BENEFIT study.

The Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial randomized patients receiving a living or standard criteria deceased donor kidney transplant to a more (MI) or less intensive (LI) regimen of belatacept or cyclosporine A (CsA). The 5-year results of the long-term extension (LTE) cohort are reported. A total of 456 (68.5% of intent-to-treat) patients entered the LTE at 36 months; 406 patients (89%) completed 60 months. Between Months 36 and 60, death occurred in 2%, 1% and 5% of belatacept MI, belatacept LI and CsA patients, respectively; graft loss occurred in 0% belatacept and 2% of CsA patients. Acute rejection between Months 36 and 60 was rare: zero belatacept MI, one belatacept LI and one CsA. Rates for infections and malignancies for Months 36-60 were generally similar across belatacept groups and CsA, respectively: fungal infections (14%, 15%, 12%), viral infections (21%, 18%, 16%) and malignancies (6%, 6%, 9%). No new posttransplant lymphoproliferative disorder cases occurred after 36 months. Mean calculated GFR (MDRD, mL/min/1.73 m(2) ) at Month 60 was 74 for belatacept MI, 76 for belatacept LI and 53 for CsA. These results show that the renal function benefit and safety profile observed in belatacept-treated patients in the early posttransplant period was sustained through 5 years.

The natural history of clinical operational tolerance after kidney transplantation through twenty-seven cases.

We report here on a European cohort of 27 kidney transplant recipients displaying operational tolerance, compared to two cohorts of matched kidney transplant recipients under immunosuppression and patients who stopped immunosuppressive drugs and presented with rejection. We report that a lower proportion of operationally tolerant patients received induction therapy (52% without induction therapy vs. 78.3%[p = 0.0455] and 96.7%[p = 0.0001], respectively), a difference likely due to the higher proportion (18.5%) of HLA matched recipients in the tolerant cohort. These patients were also significantly older at the time of transplantation (p = 0.0211) and immunosuppression withdrawal (p = 0.0002) than recipients who rejected their graft after weaning. Finally, these patients were at lower risk of infectious disease. Among the 27 patients defined as operationally tolerant at the time of inclusion, 19 still display stable graft function (mean 9 ± 4 years after transplantation) whereas 30% presented slow deterioration of graft function. Six of these patients tested positive for pre-graft anti-HLA antibodies. Biopsy histology studies revealed an active immunologically driven mechanism for half of them, associated with DSA in the absence of C4d. This study suggests that operational tolerance can persist as a robust phenomenon, although eventual graft loss does occur in some patients, particularly in the setting of donor-specific alloantibody.

Transfer of peanut allergy following lung transplantation: a case report.

This case study describes a patient who developed peanut allergy following lung transplantation. A 54-year-old woman underwent bilateral lung transplantation on June 2009 owing to severe chronic obstructive pulmonary disease. She had no history of food allergy before transplantation. The donor, however, was a 20-year-old man who was fatally injured during an automobile accident; he was allergic to peanuts. At 3 months after transplantation, the lung recipient presented with acute dyspnea and urticaria 15 minutes after consuming food containing peanut derivatives. Pre- and posttransplantation recipient blood samples analyzed for the presence of IgE antibodies specific for peanut allergens confirmed that the allergy had been passively transfered as a consequence of transplantation. Food allergy following solid organ transplantation is thought to be rare, mostly occurring in children. Two mechanisms may explain the observations described for the patient reported in this study: de novo development of peanut allergies after transplantation, or passive transfer of peanut allergies from a peanut-sensitized organ donor. This case report documenting pre- and posttransplantation IgE status in a lung transplantation case suggested that the allergic status of organ donors should be thoroughly assessed before transplantation, and potential allergy transfer risks must be discussed with the transplant team and the patient.

Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up.

Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term.

[Solid tumors after kidney transplantation]. / Tumeurs solides après transplantation rénale.

The overall risk of cancer in the kidney transplant patient is three to five times higher than the risk in the general population, and the risk of cutaneous epitheliomas, the most frequent, is multiplied by 100. There are many causes of posttransplantation cancer involving modifications in the immunosurveillance of neoplastic cells, viral reactivation or an increase in viral infections, genetic or acquired risks, but also immunosuppressors. Azathioprine and anticalcineurins in particular are associated with an increase in cancer risk. This is why at-risk patients should be monitored closely before and after transplantation. During the pretransplantation period, the risk factors present should be eradicated and the patient screened for cancers. In the posttransplantation period, prevention is indispensable, with regular screening for cancer, sun protection, and induction treatment adapted to the risk present. In transplantation patients who have developed cancer, immunosuppression can, however, be preserved using proliferation signal inhibitors, which present useful anti-tumor activity at doses that are effective for immunosuppression. Effective treatment of the cancer can now be expected without systematically losing the graft after interrupting the transplantation treatment.

Zygomycosis caused by Cunninghamella bertholletiae in a kidney transplant recipient.

Infections caused by Cunninghamella bertholletiae are rare but severe. Only 32 cases have been reported as yet, but in 26 of these this species was a contributing cause of the death of the patient. This opportunistic mould in the order Mucorales infects immunocompromized patients suffering from haematological malignancies or diabetes mellitus, as well as solid organ transplant patients. The lung is the organ most often involved. Two cases of primary cutaneous infection have been previously reported subsequent to soft-tissue injuries. We report a case of primary cutaneous C. bertholletiae zygomycosis in a 54-year-old, insulin-dependent diabetic man who was treated with tacrolimus and steroids after kidney transplantation. No extracutaneous involvement was found. In this patient, the infection may have been related to insulin injections. The patient recovered after an early surgical excision of the lesion and daily administration of itraconazole for 2 months. This case emphasizes the importance of an early diagnosis of cutaneous zygomycosis, which often presents as necrotic-looking lesions. Prompt institution of antifungal therapy and rapid surgical intervention are necessary to improve the prospects of patients who have contracted these potentially severe infections.

[Systemic embolism in a renal transplant patient. Echocardiographic demonstration of bronchial carcinoma with intracardiac invasion]. / Embolie artérielle chez une greffée rénale. Découverte échocardiographique d'un cancer bronchique à extension intracardiaque.

A 45 year old female renal transplant patient was admitted for subacute ischaemia of a lower limb. Echocardiography was performed and showed the presence of bronchial carcinoma with intracardiac invasion. The tumour was confirmed by thoracic computerised tomography and by bronchoscopy. Histological investigation of bronchial biopsies and of the arterial embolism extracted at surgery showed large cell malignant disease. The tumour partially responded to chemotherapy and the patient survived for 5 months. Extension of a bronchial carcinoma to the left atrium is a classical complication in autopsy reports but rarely a source of systemic embolism. Echocardiographic diagnosis of this condition is very rare. The incidence of malignant diseases is higher in renal transplant patients than in the general population but this has not been verified for bronchial carcinoma. Echocardiography played an essential role in this case, detecting the tumour and its extension, indicating a poor prognosis and guiding treatment.

Nephrogenic adenoma of the bladder in renal transplant recipients: a report of 9 cases with assessment of deoxyribonucleic acid ploidy and long-term followup.

PURPOSE: We evaluated the outcome of nephrogenic adenoma, a benign tumor rarely encountered in renal transplant recipients. MATERIALS AND METHODS: Between 1985 and 1993, 9 renal transplant recipients with a nephrogenic bladder adenoma removed by endoscopic resection were followed for 24 to 88 months (mean 40). Tumor deoxyribonucleic acid ploidy was assessed by flow cytometry at diagnosis and/or relapse. RESULTS: The relapse rate was 88%. The tumors were diploid and of low proliferating potential, and showed no malignant transformation. CONCLUSIONS: Our study confirms the lack of premalignant potential of nephrogenic adenomas. However, since transplant recipients might be at increased risk for bladder cancer, they should be followed closely.

Lack of effect of isradipine on cyclosporin pharmacokinetics.

The influence of isradipine as a long acting form (IcazR LP 5 mg) on cyclosporin pharmacokinetics was studied in six hypertensive renal transplant patients (mean age 37 yrs; mean body weight 62 kg). These patients received a mean daily cyclosporin dose of 307 mg in two equal intakes. Isradipine was orally administered once a day at a dose of 5 mg before the morning cyclosporin intake. Cyclosporin kinetics was assessed over a 0-12-h period, the day before (D-1) and 13 days (D+13) after isradipine treatment. Whole blood concentrations of cyclosporin were determined by radioimmunoassay (RIA) using the SandimmuneR-RIA kit (specific and non-specific monoclonal antibodies). Area under the blood concentration-time curve (AUC), the maximum blood concentration (Cmax) and the time to reach Cmax (Tmax) on D-1 and D+13 were not significantly different whatever the specificity of the RIA method. For example, the mean AUC +/- sd values were 5,247 +/- 2,255 (D-1) vs 5,317 +/- 1,675 (D+13) microgram.1(-1).h for the specific and 20,905 +/- 8,317 vs 19,327 +/- 5,758 microgram.1(-1).h for the non-specific determinations. Therefore, the pharmacokinetics of cyclosporin is not influenced by co-administration of isradipine at a therapeutic dosage. Moreover, the clinical results show that isradipine treatment was effective after 13 days administration (mean systolic blood pressure 132 vs 158 mm Hg, P < 0.05 and mean diastolic blood pressure 77 vs 93 mm Hg, P < 0.05 in supine position), and well tolerated throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

[Comparison of radiologic lesions of rheumatoid polyarthritis in function of the presence or the absence of the rheumatoid factor IgA]. / Comparaison des lésions radiologiques de la polyarthrite rhumatoïde en fonction de la présence ou de l'absence de facteur rhumatoïde IgA.

The authors compared, with the help of five radiological indices bearing on part (hand and wrists) or the all the articulations of the limbs concerned by rheumatoid arthritis (RA), a group of 45 RA with rheumatoid factor IgA (RF IgA) with a group of 45 RA without RF IgA by matching them according to age, sex and duration of evolution. They did not find any significant difference between the two groups for any of the indices. Although they are more often associated with agglutinant RF IgM, the RA with RF IgA are not more severe on the radiological level than the RA without FR IgA.