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Daratumumab, a humanized anti-CD38 monoclonal antibody, has demonstrated anti-plasma cell activity alone and in combination with other drugs in multiple myeloma (MM) and in light chain amyloidosis (AL). Allogenic anti-Human leukocyte antigen (HLA) antibodies are frequently encountered in patients awaiting kidney transplantation, complicating the access to a compatible transplant and represent a major risk factor of humoral rejection. Durably removing the antibodies or eliminating the producing cells is an objective that is currently out of reach. The objectives of our study were to evaluate the frequency of anti-HLA antibodies in MM and AL patients, and to determine the effect of daratumumab on them. Eligible patients with diagnosed MM or AL were selected (n = 182), among whom 84 had anti HLA antibodies (46%). Forty-nine patients (45 MM and 4 AL) were retrospectively included. Patients were treated with a combination of an alkylating agent, an immunomodulatory imide drug (IMiD), a Proteasome inhibitor, with (n = 22) or without (n = 22) daratumumab. Five patients received daratumumab alone. Treatment with daratumumab lowered anti-HLA antibodies in 85% (23/27) of cases including complete loss in 56% of cases (15/27) compared to 77% (17/22) and 45% (10/22) respectively, p = 0.8. This study couldn’t find a statistic impact of daratumumab to lower HLA antibody in this cohort. The association with chemotherapy could be an important bias and this hypothesis will be evaluated in ongoing studies enrolling patients undergoing kidney transplantation.

Background Human Norovirus (HuNoV) has recently been identified as a major cause of diarrhea among kidney transplant recipients (KTR). Data regarding risk factors associated with the occurrence of HuNoV infection, and its long-term impact on kidney function are lacking. Methods We conducted a retrospective case-control study including all KTR with a diagnosis of HuNoV diarrhea. Each case was matched to a single control according to age and date of transplantation, randomly selected among our KTR cohort and who did not develop HuNoV infection. Risk factors associated with HuNoV infection were identified using conditional logistic regression, and survival was estimated using Kaplan-Meier estimator. Results From January 2012 to April 2018, 72 cases of NoV diarrhea were identified among 985 new KT, leading to a prevalence of HuNoV infection of 7.3%. Median time between kidney transplantation and diagnosis was 46.5 months (Inter Quartile Range [IQR]:17.8–81.5), and the median duration of symptoms 40 days (IQR: 15–66.2). Following diagnosis, 93% of the cases had a reduction of immunosuppression. During follow-up, de novo Donor Specific Antibody (DSA) were observed in 8 (9%) cases but none of the controls (p = 0.01). Acute rejection episodes were significantly more frequent among cases (13.8% versus 4.2% in controls; p = 0,03), but there was no difference in serum creatinine level at last follow-up between the two groups (p = 0.08). Pre-transplant diabetes and lymphopenia below 1000/mm3 were identified as risks factors for HuNoV infection in multivariate analysis. Conclusion HuNoV infection is a late-onset and prolonged infection among KTR. The current management, based on the reduction of immunosuppressive treatment, is responsible for the appearance of de novo DSA and an increase in acute rejection episodes.

While either pancreas or pancreatic islet transplantation can restore endogenous insulin secretion in patients with diabetes, no beta-cell replacement strategies are recommended in the literature. For this reason, the aim of this national expert panel statement is to provide information on the different kinds of beta-cell replacement, their benefit-risk ratios and indications for each type of transplantation, according to type of diabetes, its control and association with end-stage renal disease. Allotransplantation requires immunosuppression, a risk that should be weighed against the risks of poor glycaemic control, diabetic lability and severe hypoglycaemia, especially in cases of unawareness. Pancreas transplantation is associated with improvement in diabetic micro- and macro-angiopathy, but has the associated morbidity of major surgery. Islet transplantation is a minimally invasive radiological or mini-surgical procedure involving infusion of purified islets via the hepatic portal vein, but needs to be repeated two or three times to achieve insulin independence and long-term functionality. Simultaneous pancreas-kidney and pancreas after kidney transplantations should be proposed for kidney recipients with type 1 diabetes with no surgical, especially cardiovascular, contraindications. In cases of high surgical risk, islet after or simultaneously with kidney transplantation may be proposed. Pancreas, or more often islet, transplantation alone is appropriate for non-uraemic patients with labile diabetes. Various factors influencing the therapeutic strategy are also detailed in this report.

Early acute renal failure (ARF) is a common complication after lung transplantation (LTx), and is associated with higher long-term mortality. Calcineurins inhibitors (CNIs) toxicity play a major role in ARF in the early phase post-LTx, and alternate nonnephrotoxic immunosuppressive (IS) regimen are needed in LTx. Belatacept, a novel immunosuppressant that blocks a T-cell costimulation pathway, is a nonnephrotoxic drug indicated as an alternative to CNIs in kidney Tx. In LTx, a few cases of CNI-belatacept conversion have been reported so far, only in the late long-term follow-up (>3 years post-LTx). We here report a single-center series of 4 LTx recipients converted to a belatacept primary IS-regimen in the early-postoperative period after LTx (month [M] 2, M2, M2, M5). Causes of conversion were persistent severe renal failure, due to: [1] thrombotic microangiopathy; [2] CNI toxicity/acute tubular necrosis (ATN); [3] ATN/FSglomerulosclerosis; [4] CNI toxicity. Following belatacept-conversion, acute rejection (AR) episodes occurred in 2 high immunologic risk recipients, with detection of donor-specific antibodies (asymptomatic AR both in patient 1 [graded A2B0] and patient 2 [A2Bx], which were both resolved with pulsed steroids). All 4 recipients remained with stable pulmonary function and significant renal function improvement at last available follow-up postbelatacept (M2, M3, M3, and M4). Outcome at 9 months postbelatacept, including incidence of AR and chronic lung allograft dysfunction, graft survival, and renal function outcome will be presented at the ERS 2017 congress.

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.

Tumor cells with donor genotype have been identified in human skin cancer after allogeneic transplantation; however, the donor contribution to the malignant epithelium has not been established. Kidney transplant recipients have an increased risk of invasive skin squamous cell carcinoma (SCC), which is associated with accumulation of the tumor suppressor p53 and TP53 mutations. In 21 skin SCCs from kidney transplant recipients, we systematically assessed p53 expression and donor/recipient origin in laser-microdissected p53+ tumor cells. In one patient, molecular analyses demonstrated that skin tumor cells had the donor genotype and harbored a TP53 mutation in codon 175. In a kidney graft biopsy performed 7 years before the skin SCC diagnosis, we found p53+ cells in the renal tubules. We identified the same TP53 mutation in these p53+ epithelial cells from the kidney transplant. These findings provide evidence for a donor epithelial cell contribution to the malignant skin epithelium in the recipient in the setting of allogeneic kidney transplantation. This finding has theoretical implications for cancer initiation and progression and clinical implications in the context of prolonged immunosuppression and longer survival of kidney transplant patients.

The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-based equation was developed to address the systematic underestimation of the glomerular filtration rate (GFR) by the Modification of Diet in Renal Disease (MDRD) Study equation in patients with a relatively well-preserved kidney function. The performance of the new equation for kidney transplant recipients is discussed.We analyzed the performances of the CKD-EPI equation in comparison with the MDRD Study equation in 825 stable kidney transplant recipients. Bias, precision, and accuracy within 30% of true GFR were determined. GFR was measured by urinary clearance of inulin (n=488) and plasma clearance of Cr-EDTA (n=337).Mean measured GFR (mGFR) was 50±19 mL/min/1.73 m. On the whole cohort, bias was significantly lower for MDRD Study equation compared with CKD-EPI creatinine. This superiority translates into a better accuracy (80% and 74% for the MDRD and CKD-EPI creatinine, respectively). The best performance of the MDRD Study equation is confirmed both in the subgroups of patients with mGFR60 mL/min/1.73 m and between 60 and 90 mL/min/1.73 m. For mGFR90 mL/min/1.73 m, there were no significant differences between the two equations in terms of performance.The CKD-EPI creatinine equation does not offer a better GFR prediction in renal transplant patients compared with the MDRD Study equation, even in the earlier CKD stages.

ABC-incompatible (ABOi) living donor renal transplantation is being developed since the 80s, and may provide a significant source of organs. Blood group A and B antigens are expressed not only on red blood cells but also on renal vascular endothelial and renal epithelial membranes. Each individual has preformed natural antibodies against his/ her absent A and/or B antigens. These antibodies may directly damage the ABOi allograft and cause its diffuse thrombosis and primary non-function. ABOi allogratf recipients are conditioned with one dose of rituximab (as a "pharmacological splenectomy") and oral immunosuppressive treatment is introduced several days pre-operatively. Anti A/B titers are lowered by plasmapheresis or specific immunoadsorption. Close follow-up is mandatory in the first two weeks after transplantation, due to higher acute humoral rejection risk, until reaching an "accommodation" state. Thereafter, graft and patient survivals are the same as those of ABO compatible renal transplantations.

Purpose Post-transplantation lymphoproliferative disorder (PTLD) is associated with significant mortality in kidney transplant recipients. We conducted a prospective survey of the occurrence of PTLD in a French nationwide population of adult kidney recipients over 10 years. Patients and Methods A French registry was established to cover a nationwide population of transplant recipients and prospectively enroll all adult kidney recipients who developed PTLD between January 1, 1998, and December 31, 2007. Five hundred patient cases of PTLD were referred to the French registry. The prognostic factors for PTLD were investigated using Kaplan-Meier and Cox analyses. Results Patients with PTLD had a 5-year survival rate of 53% and 10-year survival rate of 45%. Multivariable analyses revealed that age > 55 years, serum creatinine level > 133 μmol/L, elevated lactate dehydrogenase levels, disseminated lymphoma, brain localization, invasion of serous membranes, monomorphic PTLD, and T-cell PTLD were independent prognostic indicators of poor survival. Considering five variables at diagnosis (age, serum creatinine, lactate dehydrogenase, PTLD localization, and histology), we constructed a prognostic score that classified patients with PTLD as being at low, moderate, high, or very high risk for death. The 10-year survival rate was 85% for low-, 80% for moderate-, 56% for high-, and 0% for very high–risk recipients. Conclusion This nationwide study highlights the prognostic factors for PTLD and enables the development of a new prognostic score. After validation in an independent cohort, the use of this score should allow treatment strategies to be better tailored to individual patients in the future.

Practices for enrollment on kidney transplantation waiting lists are variable between geographical areas and centers. Early referral of patients with chronic renal failure (CRF) to a nephrologist, particularly one practicing in a transplantation center, is a prerequisite to early enrollment. Despite improved survival in elderly transplant recipients, being aged over 65 years is still a barrier against enrollment. Furthermore certain comorbid conditions such as diabetes mellitus are often wrongly considered as contraindications for transplantation. If nephrological management is initiated early, enrollment could (should?) be considered before the terminal phase of CRF, with the hope of preemptive transplantation with the known advantages not only for the individual recipient but also for the community in general. Glomerular filtration rate below 20 ml/minute could be a reasonable cutoff for enrollment. Patients referred late to a nephrologist will require dialysis. Dialysis center staff should be well trained in delivering appropriate information on kidney transplantation and initiating evaluation. A consultation with a transplantation specialist should be rapidly scheduled.

A role for cytomegalovirus (CMV) infection in the etiologies of acute and chronic rejection in renal allograft recipients has been suggested. We previously reported that preemptive treatment of CMV infection with ganciclovir in kidney transplant patients was safe and effective. We now present a retrospective analysis of 169 consecutive renal transplant patients, of whom 87 (51.5%) received preemptive treatment with ganciclovir (CMV(+) group). No patient died of CMV infection. Actuarial graft and patient survival rates were not different between the CMV(+) and the CMV(-) groups (graft survival: 68% and 69%; patient survival: 89% and 88%, respectively). At the end of the study, the mean plasma creatinine levels were not statistically different between the two groups (185+/-13 and 166+/-12 micromol/L for the CMV(+) group and the CMV(-) group, respectively). These results suggest that preemptive treatment of CMV infection with ganciclovir may prevent the CMV-induced renal injury and graft loss.