Opportunistic infections after conversion to belatacept in kidney transplantation.

BACKGROUND: Belatacept (bela) rescue therapy seems to be a valuable option for calcineurin inhibitor chronic toxicity in kidney transplantation. Nevertheless, the risk of infection associated with bela is not well reported. METHODS: We report the rate of opportunistic infections (OPI) after a switch to bela in a multicentric cohort of 280 kidney transplant patients. RESULTS: Forty-two OPI occurred in 34 patients (12.1%), on average 10.8 ± 11.3 months after the switch. With a cumulative exposure of 5128 months of bela treatment, we found an incidence of 0.008 OPI/month of exposure, and 9.8 OPI/100 person-years. The most common OPI was cytomegalovirus (CMV) disease in 18/42 OPI (42.9%) and pneumocystis pneumonia in 12/42 OPI (28.6%). Two patients presented a progressive multifocal leucoencephalopathy and two patients developed a cerebral Epstein-Barr virus-induced post-transplant lymphoproliferative disease. OPI led to death in 9/34 patients (26.5%) and graft failure in 4/34 patients (11.8%). In multivariate analysis, estimated glomerular filtration rate <25/mL/min/1.73 m2 on the day of the switch and the use of immunosuppressive agents before transplantation were associated with the occurrence of OPI. We found a higher rate of infection-related hospitalization (24.1 versus 12.3/100 person-years, P = 0.0007) and also a higher rate of OPI (13.2 versus 6.7/100 person-years, P = 0.005) in the early conversion group (within 6 months). CONCLUSIONS: The risk of OPI is significant post-conversion to bela and may require additional monitoring and prophylactic therapy, particularly regarding pneumocystis pneumonia and CMV disease. These data need to be confirmed in a larger case-control study.

Recurrence of Renal Cell Cancer After Renal Transplantation in a Multicenter French Cohort.

BACKGROUND: Renal cancer accounts for 3% of adult malignancies; renal cell carcinoma (RCC) represents 80% of all renal cancers, and is characterized by late recurrences. Recurrences after kidney transplantation are associated with a high mortality rate. We aimed to determine if recurrences are linked to tumor characteristics and to delays between diagnosis and transplantation. METHODS: We retrospectively analyzed data from French kidney-transplanted patients with medical histories of pretransplant renal cancer, focusing on the most common histological subtypes: clear cell and papillary cancers. Characteristics of the tumors, patients, and kidney transplantations were documented, and posttransplant patient survival was analyzed. RESULTS: Of 143 patients, 13 experienced cancer recurrence after kidney transplantation. The mean delay in recurrence was 3 ± 2.3 years posttransplantation, and the cumulative incidences of recurrence were 7.7% at 5 years and 14.9% at 10 years. The risk of recurrence was higher in patients with clear cell RCC (13% vs 0%, P = 0.015). There was no correlation between posttransplant recurrence and the interval before transplantation. Factors associated with a higher risk of cancer recurrence were histological clear cell RCC (P = 0.025), tumor stage pT2 (P = 0.002), and Fuhrman grade IV (P < 0.001). Recurrences were associated with a high mortality rate; 76.9% of patients with recurrences had died by the end of the follow-up period. CONCLUSIONS: Recurrences of clear cell RCC are not uncommon after kidney transplantation and are associated with very poor prognoses. These results should be considered before listing patients with a history of renal cancer for transplantation.

A French Cohort Study of Kidney Retransplantation after Post-Transplant Lymphoproliferative Disorders.

BACKGROUND AND OBJECTIVES: Post-transplant lymphoproliferative disorders arising after kidney transplantation portend an increased risk of morbidity and mortality. Retransplantation of patients who had developed post-transplant lymphoproliferative disorder remains questionable owing to the potential risks of recurrence when immunosuppression is reintroduced. Here, we investigated the feasibility of kidney retransplantation after the development of post-transplant lymphoproliferative disorder. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We reviewed the data from all patients who underwent kidney retransplantation after post-transplant lymphoproliferative disorder in all adult kidney transplantation centers in France between 1998 and 2015. RESULTS: We identified a total of 52 patients with kidney transplants who underwent 55 retransplantations after post-transplant lymphoproliferative disorder. The delay from post-transplant lymphoproliferative disorder to retransplantation was 100±44 months (28-224); 98% of patients were Epstein-Barr virus seropositive at the time of retransplantation. Induction therapy for retransplantation was used in 48 patients (i.e., 17 [31%] patients received thymoglobulin, and 31 [57%] patients received IL-2 receptor antagonists). Six patients were also treated with rituximab, and 53% of the patients received an antiviral drug. The association of calcineurin inhibitors, mycophenolate mofetil, and steroids was the most common maintenance immunosuppression regimen. Nine patients were switched from a calcineurin inhibitor to a mammalian target of rapamycin inhibitor. One patient developed post-transplant lymphoproliferative disorder recurrence at 24 months after retransplantation, whereas post-transplant lymphoproliferative disorder did not recur in 51 patients. CONCLUSIONS: The recurrence of post-transplant lymphoproliferative disorder among patients who underwent retransplantation in France is a rare event.

Plasma cell neoplasia after kidney transplantation: French cohort series and review of the literature.

Although post-transplant lymphoproliferative disorder (PTLD) is the second most common type of cancer in kidney transplantation (KT), plasma cell neoplasia (PCN) occurs only rarely after KT, and little is known about its characteristics and evolution. We included twenty-two cases of post-transplant PCN occurring between 1991 and 2013. These included 12 symptomatic multiple myeloma, eight indolent myeloma and two plasmacytomas. The median age at diagnosis was 56.5 years and the median onset after transplantation was 66.7 months (2-252). Four of the eight indolent myelomas evolved into symptomatic myeloma after a median time of 33 months (6-72). PCN-related kidney graft dysfunction was observed in nine patients, including six cast nephropathies, two light chain deposition disease and one amyloidosis. Serum creatinine was higher at the time of PCN diagnosis than before, increasing from 135.7 (±71.6) to 195.9 (±123.7) µmol/l (p = 0.008). Following transplantation, the annual rate of bacterial infections was significantly higher after the diagnosis of PCN, increasing from 0.16 (±0.37) to 1.09 (±1.30) (p = 0.0005). No difference was found regarding viral infections before and after PCN. Acute rejection risk was decreased after the diagnosis of PCN (36% before versus 0% after, p = 0.004), suggesting a decreased allogeneic response. Thirteen patients (59%) died, including twelve directly related to the hematologic disease. Median graft and patient survival was 31.7 and 49.4 months, respectively. PCN after KT occurs in younger patients compared to the general population, shares the same clinical characteristics, but is associated with frequent bacterial infections and relapses of the hematologic disease that severely impact the survival of grafts and patients.

Anti-TNFα therapy for chronic inflammatory disease in kidney transplant recipients: Clinical outcomes.

Anti-tumor necrosis factor-α (TNFα) therapy has improved the prognosis of many chronic inflammatory diseases. It appears to be well-tolerated by liver-transplant patients. However, their use and their safety in kidney-transplant patients have yet to be determined.In this retrospective study, we identified 16 adult kidney-transplant patients aged 46.5 years (34-51.8) who received anti-TNFα therapy from 7 kidney transplantation centers. The indications for this treatment included: chronic inflammatory bowel disease (n = 8), inflammatory arthritis (n = 5), AA amyloidosis (n = 1), psoriasis (n = 1), and microscopic polyangiitis (n = 1).Anti-TNFα therapies resulted in a clinical response in 13/16 patients (81%). Estimated glomerular filtration rates (MDRD-4) were similar on day 0 and at 24 months (M24) after anti-TNFα treatment had been initiated (41 [12-55] and 40 [21-53] mL/min/1.73 m, respectively). Two allograft losses were observed. The 1st case was due to antibody-mediated rejection (M18), while the 2nd was the result of AA amyloidosis recurrence (M20). There were several complications: 8 patients (50%) developed 23 serious infections (18 bacterial, 4 viral, and 1 fungal) and 4 developed cancer. Five patients died (infection n = 2, cardiac AA amyloidosis n = 1, intraalveolar hemorrhage following microscopic polyangiitis n = 1, and acute respiratory distress syndrome n = 1). On univariate analysis, recipient age associated with death (P = 0.009) and infection development (P = 0.06).Using anti-TNFα therapies, remission can be achieved in chronic inflammatory diseases in kidney-transplant patients. However, concommitant anti-TNFα and immunosuppresive therapies must be used with caution due to the high risk of infection, particularly after the age of 50.

Minimization of maintenance immunosuppressive therapy after renal transplantation comparing cyclosporine A/azathioprine or cyclosporine A/mycophenolate mofetil bitherapy to cyclosporine A monotherapy: a 10-year postrandomization follow-up study.

Long-term outcomes in renal transplant recipients withdrawn from steroid and submitted to further minimization of immunosuppressive regimen after 1 year are lacking. In this multicenter study, 204 low immunological risk kidney transplant recipients were randomized 14.2 ± 3.7 months post-transplantation to receive either cyclosporine A (CsA) + azathioprine (AZA; n = 53), CsA + mycophenolate mofetil (MMF; n = 53), or CsA monotherapy (n = 98). At 3 years postrandomization, the occurrence of biopsy for graft dysfunction was similar in bitherapy and monotherapy groups (21/106 vs. 26/98; P = 0.25). At 10 years postrandomization, patients' survival was 100%, 94.2%, and 95.8% (P = 0.25), and death-censored graft survival was 94.9%, 94.7%, and 95.2% (P = 0.34) in AZA, MMF, and CsA groups, respectively. Mean estimated glomerular filtration rate was 70.4 ± 31.1, 60.1 ± 22.2, and 60.1 ± 19.0 ml/min/1.73 m(2), respectively (P = 0.16). The incidence of biopsy-proven acute rejection was 1.4%/year in the whole cohort. None of the patients developed polyomavirus-associated nephropathy. The main cause of graft loss (n = 12) was chronic antibody-mediated rejection (n = 6). De novo donor-specific antibodies were detected in 13% of AZA-, 21% of MMF-, and 14% of CsA-treated patients (P = 0.29). CsA monotherapy after 1 year is safe and associated with prolonged graft survival in well-selected renal transplant recipient (ClinicalTrials.gov number: 980654).

Eight-year results of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in renal transplantation.

We present the results at 8 years of the Spiesser study, a randomized trial comparing de novo sirolimus and cyclosporine in kidney transplant recipients at low immunologic risk. We assessed estimated glomerular filtration (eGFR), graft, patient, and death-censored graft survival (log-rank compared), de novo DSA appearance, risk of malignancy, post-transplant diabetes mellitus (PTDM), and anemia. Intent-to-treat and on-treatment analyses were performed. Graft survival was similar in both groups (sirolimus: 73.3%, cyclosporine: 77.7, P = 0.574). No difference was observed between treatment groups concerning patient survival (P = 0.508) and death-censored graft survival (P = 0.858). In conditional intent-to-treat analysis, mean eGFR was greater in sirolimus than in cyclosporine group (62.5 ± 27.3 ml/min vs. 47.8 ± 17.1 ml/min, P = 0.004), in particular because graft function was excellent in patients maintained under sirolimus (eGFR = 74.0 ml/min). Importantly, no detrimental impact was observed in patients in whom sirolimus has been withdrawn (eGFR = 49.5 ml/min). Overall, 17 patients showed de novo DSAs, with no difference between the two groups (P = 0.520). Malignancy did not differ by treatment. An initial maintenance regimen based on sirolimus provides a long-term improvement in renal function for kidney transplant patients, especially for those maintained on sirolimus.

Bronchiectasis diagnosed after renal transplantation: a retrospective multicenter study.

BACKGROUND: Bronchiectasis is characterized by abnormal, permanent and irreversible dilatation of the bronchi, usually responsible for daily symptoms and frequent respiratory complications. Many causes have been identified, but only limited data are available concerning the association between bronchiectasis and renal transplantation. METHODS: We conducted a retrospective multicenter study of cases of bronchiectasis diagnosed after renal transplantation in 14 renal transplantation departments (French SPIESSER group). Demographic, clinical, laboratory and CT scan data were collected. RESULTS: Forty-six patients were included (mean age 58.2 years, 52.2 % men). Autosomal dominant polycystic kidney disease (32.6 %) was the main underlying renal disease. Chronic cough and sputum (50.0 %) were the major symptoms leading to chest CT scan. Mean duration of symptoms before diagnosis was 1.5 years [0-12.1 years]. Microorganisms were identified in 22 patients, predominantly Haemophilus influenzae. Hypogammaglobulinemia was observed in 46.9 % patients. Bronchiectasis was usually extensive (84.8 %). The total bronchiectasis score was 7.4 ± 5.5 with a significant gradient from apex to bases. Many patients remained symptomatic (43.5 %) and/or presented recurrent respiratory tract infections (37.0 %) during follow-up. Six deaths (13 %) occurred during follow-up, but none were attributable to bronchiectasis. CONCLUSIONS: These results highlight that the diagnosis of bronchiectasis should be considered in patients with de novo respiratory symptoms after renal transplantation. Further studies are needed to more clearly understand the mechanisms underlying bronchiectasis in this setting.