How to improve clotting factors depletion in double-filtration plasmapheresis.

BACKGROUND: Double-filtration plasmapheresis (DFPP), a selective therapeutic apheresis, can deplete pathogenic antibodies/substances, but also important coagulation factors. AIM: To determine if the use of a separator filter with different characteristics (CascadefloEC-50 W) as compared to the reference filter (PlasmafloOP-08 W) is as efficient in terms of immunoglobulin loss, but can reduce coagulation factor losses and have similar tolerability. PATIENTS/METHODS: This is a single-center prospective study including 14 patients divided into two groups (7 each): that is, group1 = CascadefloEC-50 W and group2 = PlasmafloOP-08 W. We measured immunoglobulins, lipid profiles, blood-cell counts, hemostasis (prothrombin time, activated partial thromboplastin time), coagulation factors, and natural anticoagulants at before and after the first DFPP-session. RESULTS: In group 1, the loss of coagulation factors was significantly reduced as compared to group 2 for proteins with a molecular weight of >150 kDa: there was, respectively, an average decrease of 70% vs 31% for fibrinogen (P = 0.004), 66% vs 21% for factor V (P = 2.16e-07), 60% vs 32% for factor XI (P = 6.96e-06), 75% vs 17% for XIII-antigen (P = 0.0002), and 47% vs 0% for VWF-antigen(P = 0.02). The decrease in post-session IgG was, on average, 45% in group 1 and 50% in group 2 (P = 0.13). Those results remained significant even when adjusted to the treated-plasma volume and the pre-DFPP factor values. CONCLUSION: DFPP, using a CascadefloEC-50W as a first-filter, reduces efficiently IgGs similarly to PlasmafloOP-08W but spares clotting factors.

Isoagglutinin removal by plasma centrifugation or filtration (single or double): A prospective study in a single center.

INTRODUCTION: ABO-incompatible (ABOi) kidney transplantation, a well-established procedure, has good long-term results provided pretransplant desensitization that includes immunosuppression and apheresis. OBJECTIVE: To compare, within the first pretransplant apheresis session given to 29 ABOi kidney-transplant candidates, the effect on isoagglutinin titers (both IgG and IgM isotypes) of three modalities: centrifugation therapeutic plasmapheresis (cTP; n = 10), filtration TP (fTP; n = 9), and double-filtration plasmapheresis (DFPP; n = 10). RESULTS: The three groups were comparable according to baseline demographics. Treated plasma volumes were similar across the three groups, that is, 4111 ± 403 mL (cTP), 3861 ± 282 mL (fTP), and 3699 ± 820 mL (DFPP): that is, 54 ± 7, 53 ± 7, and 53 ± 10 mL/kg respectively. One session of centrifugation or filtration TP reduced IgG anti-A/anti-B isoagglutinin titer by ~4, whereas one DFPP session reduced it by ~2. One session of cTP reduced IgM anti-A isoagglutinin titer by a little less than 4, whereas fTP and DFPP sessions reduced it by ~3. There were no statistical differences across the three groups regarding isoagglutinin rebound (IgG and IgM). However, isoagglutinin IgG rebound was >4 dilutions for anti-B titers compared with ~2 dilutions for anti-A titers. The median decreases in IgG level were -3.9 g/L (DFPP), -5.9 g/L (cTP), and - 6.06 g/L (fTP) (p = ns). Median fibrinogen depletions were ~ 60% (fTP), 64% (DFPP), and 76% (cTP). CONCLUSIONS: Isoagglutinin depletions within the first apheresis session were similar across cTP, fTP, and DFPP: this was numerically lower for DFPP.

Immunoadsorption for Recurrent Primary Focal Segmental Glomerulosclerosis on Kidney Allografts: A Single-Center Experience and Literature Review.

INTRODUCTION: Primary focal and segmental glomerulosclerosis (FSGS) frequently reoccurs on kidney transplants and may lead to premature allograft loss. There are no guidelines for treating FSGS recurrence on allografts; treatment is based on apheresis (plasma exchange plasmapheresis [PP], semi-specific immunoadsorption [IA] with reusable columns) plus rituximab. OBJECTIVE: We aimed to assess the efficacy of IA to treat recurrent FSGS. METHODS: We report on 7 patients with recurrent FSGS on kidney allograft (proteinuria ≥3 g/g of urinary creatinine or ≥3 g/day); they all received IA. Our primary objective was to reduce proteinuria by >50%. Patients' mean age was 45 ± 10 years. Postoperative immunosuppression relied on steroids, mycophenolate mofetil, tacrolimus, with an induction therapy of basiliximab or antithymocyte globulins. Prophylaxis to prevent FSGS recurrence was either rituximab alone (n = 3), rituximab plus either PP or IA (n = 3), or no treatment (n = 1). Mean follow-up was 20 ± 13 months. There was a median of 72 (14-101) IA sessions per patient, that is, a mean of 14 ± 1 sessions per IA column. RESULTS: At 12 months after starting IA, all patients had partial (n = 6) or complete (n = 1) remission, and allograft survival was 100%. The mean reduction in proteinuria within an IA session was 45 ± 15%. At last follow-up, 2 patients are in remission without IA, 3 patients are in partial remission that is IA dependent, and 2 patients lost their allograft due to FSGS recurrence. The most frequent adverse event was cytomegalovirus reactivation (n = 13), which subsided after valganciclovir therapy. CONCLUSIONS: We show that recurrence of FSGS can be controlled long term with IA plus rituximab. However, some patients remained dependent on IA.

Calcium-Free Dialysate Hemodialysis: A Simplified Approach.

Intermittent hemodialysis (HD) in high-bleeding-risk patients presents a challenge as circuit anticoagulation using heparin is contraindicated in such cases. Recently, the use of calcium-free citrate-containing dialysate with calcium supplementation emerged as a viable alternative to heparin-circuit anticoagulation. This is a retrospective, monocentric study to evaluate dialysis efficacy using calcium-free citrate-containing dialysate with calcium reinjection into the venous line in hemodialysis patients at risk of bleeding. A total of 53 patients were analyzed: 52 had a temporary contraindication to systemic anticoagulation (active bleeding or surgical intervention), and 1 chronic HD patient had prolonged bleeding time due to inoperable arteriovenous fistula stenosis. Only 7 out of 79 dialysis sessions performed were prematurely terminated (vascular access dysfunction). The median dialysis time was 240 min (range: 150-300). The chronic dialysis patient had 108 sessions with no premature termination. Frequent monitoring of ionized calcium was performed throughout the dialysis sessions: levels remained stable at T0 and T + 60 min (1.08 ± 0.08 mmol/L) and slightly increased at the end of the dialysis session (1.19 ± 0.13 mmol/L), remaining within normal limits. Target postfilter ionized calcium <0.4 mmol/L was achieved in all sessions (0.31 ± 0.07 mmol/L). There were no cases of symptomatic hypo-/hypercalcemia and no need for calcium infusion rate adjustment throughout the sessions. Hemodialysis with calcium-free citrate-containing dialysate and calcium reinjection into the venous line is efficient and safe in HD patients with contraindications to systemic anticoagulation.

Adverse Drug Events after Kidney Transplantation.

Introduction: Kidney transplantation stands out as the optimal treatment for patients with end-stage kidney disease, provided they meet specific criteria for a secure outcome. With the exception of identical twin donor-recipient pairs, lifelong immunosuppression becomes imperative. Unfortunately, immunosuppressant drugs, particularly calcineurin inhibitors like tacrolimus, bring about adverse effects, including nephrotoxicity, diabetes mellitus, hypertension, infections, malignancy, leukopenia, anemia, thrombocytopenia, mouth ulcers, dyslipidemia, and wound complications. Since achieving tolerance is not feasible, patients are compelled to adhere to lifelong immunosuppressive therapies, often involving calcineurin inhibitors, alongside mycophenolic acid or mTOR inhibitors, with or without steroids. Area covered: Notably, these drugs, especially calcineurin inhibitors, possess narrow therapeutic windows, resulting in numerous drug-related side effects. This review focuses on the prevalent immunosuppressive drug-related side effects encountered in kidney transplant recipients, namely nephrotoxicity, post-transplant diabetes mellitus, leukopenia, anemia, dyslipidemia, mouth ulcers, hypertension, and viral reactivations (cytomegalovirus and BK virus). Additionally, other post-kidney-transplantation drugs such as valganciclovir may also contribute to adverse events such as leukopenia. For each side effect, we propose preventive measures and outline appropriate treatment strategies.

Cryoglobulinemia and double-filtration plasmapheresis: Personal experience and literature review.

BACKGROUND: Cryoglobulinemia is defined as the presence of an abnormal immunoglobulin that may be responsible for vasculitis of small-caliber vessels. Apheresis can be used in order to temporarily eliminate circulating cryoglobulins. The aim of this study was to assess the effectiveness of apheresis (double-filtration plasmapheresis-DFPP-) in symptomatic and/or severe cryoglobulinemias. METHODS: Four male patients presenting cryoglobulinemic vasculitis and who received DFPP sessions were included. RESULTS: Their mean age was 57 ± 15 years. One patient had hepatitis-C virus (HCV)-related cryoglobulinemia and the other three patients were carriers of an IgM Kappa monoclonal gammopathy. Mean duration of follow-up was 15 ± 2 months. DFPP allowed healing of ulcerative skin lesions in the first patient and remission of nephrotic syndrome in the other patients after a median of 6(5-10) sessions. CONCLUSION: DFPP can be used safely in cryoglobulinemic-vasculitis and can be considered early to achieve a faster and sustained clinical-biological response.

Tocilizumab Evaluation in HLA-Desensitization before Kidney Transplantation as an Add-On Therapy to Apheresis: The TETRA Study.

BACKGROUND: Desensitization strategies improve access to transplantation in highly sensitized kidney transplant candidates. Tocilizumab could be a valuable addition to more traditional desensitization regimens. We investigated the effect of tocilizumab as an add-on therapy to our standard of care (SoC) desensitization strategy based on rituximab and apheresis. METHODS: In this study, we prospectively included highly sensitized patients to receive monthly tocilizumab infusions for 6 months before our SoC regimen (Toci + SoC group). We compared the reductions in the mean fluorescent intensity (MFI) rebound at post-transplantation and kidney function at 1-year post-transplantation to patients treated by SoC (based on apheresis and two doses of rituximab). RESULTS: Twenty-six patients were included in the SoC group; seven in the Toci + SoC group. Reductions in pre-transplantation MFI were similar between groups. At 1-year post-transplantation, there was no absolute difference in overall MFI rebounds, including donor-specific antibodies. Toci + SoC helped lower the rebound of antibodies with more elevated baseline MFIs. Graft function and survival rates were similar at one-year post-transplantation (median eGFR 62.8 vs. 65.6 mL/min/1.73 m2 for SoC and Toci + SoC, respectively). CONCLUSIONS: Tocilizumab as an add-on to SoC desensitization may help control the post-transplantation rebound of antibodies with elevated baseline MFIs. However, reductions in pre-transplantation MFIs were similar with or without tocilizumab. Further studies are needed to validate this pilot study.

Adverse effects of immunosuppression after liver transplantation.

After solid organ transplantation the cornerstone of immunosuppression is based on calcineurin inhibitors (CNIs), mostly tacrolimus. However, CNIs have a very narrow therapeutic window. The most important and serious side-effects of CNIs are nephrotoxicity, high blood pressure, post-transplant diabetes mellitus (PTMD), i.e., new-onset diabetes after transplantation (NODAT), dyslipidemia, and modification to the cardiovascular-risk profile. In this review, we will focus on tacrolimus-related toxicities in the setting of liver transplantation.

Belatacept Use after Kidney Transplantation and Its Effects on Risk of Infection and COVID-19 Vaccine Response.

INTRODUCTION: Belatacept is a common immunosuppressive therapy used after kidney transplantation (KT) to avoid calcineurin-inhibitor (CNI) use and its related toxicities. It is unclear whether its use exposes KT recipients (KTx) to a greater risk of infection or a poorer response to vaccines. Areas covered: We reviewed PubMed and the Cochrane database. We then summarized the mechanisms and impacts of belatacept use on the risk of infection, particularly opportunistic, in two settings, i.e., de novo KTx and conversion from CNIs. We also focused on COVID-19 infection risk and response to SARS-CoV-2 vaccination in patients whose maintenance immunosuppression relies on belatacept. Expert opinion: When belatacept is used de novo, or after drug conversion the safety profile regarding the risk of infection remains good. However, there is an increased risk of opportunistic infections, mainly CMV disease and Pneumocystis pneumonia, particularly in those with a low eGFR, in older people, in those receiving steroid-based therapy, or those that have an early conversion from CNI to belatacept (i.e.,

Kidney Transplantation for Focal Segmental Glomerulosclerosis: Can We Prevent Its Recurrence? Personal Experience and Literature Review.

BACKGROUND: Primary focal segmental glomerulosclerosis (FSGS) is associated with a high risk of recurrence after kidney transplantation with a major risk of graft loss despite preventive or curative treatments. AIM: to assess graft survival in FSGS kidney-transplant recipients and to compare those that had a relapse with those that had no relapse. PATIENTS/METHODS: we included 17 FSGS kidney-transplant recipients between January 2000 and January 2020, separated retrospectively into two groups (recurrences: n = 8 patients; no recurrences: n = 9 patients). FSGS recurrence was defined as having proteinuria of ≥3 g/g or urinary creatinine of ≥3 g/day. All patients received an induction therapy; maintenance immunosuppressive therapy at post-transplantation relied on tacrolimus/mycophenolate mofetil/steroids. In order to prevent or treat FSGS recurrence, patients received apheresis sessions plus rituximab. RESULTS: FSGS recurrence rate was 47%. All patients that relapsed with a first graft also relapsed with subsequent grafts. Median time to recurrence was 3 (min: 1; max: 4745) days, despite rituximab/apheresis prophylaxis. Mean age was significantly lower in the relapsers (group 1) than in the non-relapsers (group 2); i.e., 47 ± 11 vs. 58 ± 9 years (p = 0.04). Time to progression to stage 5 chronic kidney disease (CKD) and young age at FSGS diagnosis were lower in group 1 compared to group 2; i.e., 5 (min: 1; max: 26) vs. 2 (min: 1; max: 26) years, and 16 (min: 4; max: 55) vs. 34 (min: 6; max 48) years, respectively. There was no difference between the two groups in terms of progression to CKD stage 5 on the native kidneys, averaging 7 years in both groups (p = 0.99). In group 1, seven patients received rituximab/apheresis prophylaxis, although this did not prevent the recurrence of FSGS. CONCLUSION: pretransplant prophylaxis with plasmapheresis/rituximab did not appear to reduce the risk of recurrence of primary FSGS on the graft, but could allow remission in the event of recurrence.

Efficacy of Plasmapheresis in Nivolumab-Associated ANCA Glomerulonephritis: A Case Report and Pathophysiology Discussion.

Immune checkpoint inhibitors (ICIs) have revolutionized solid organ and hematologic cancer treatments by improving overall prognoses. However, they can lead to overactivation of the immune system and several immune-related adverse events and sometimes affecting the renal system. Although acute interstitial nephritis is well described, we know little about ICI-associated glomerular injury. Herein, we report an exceptional case of renal ANCA positive-associated vasculitis (AAV) after nivolumab therapy. Three weeks after the last nivolumab injection, the patient presented with proteinuria at 1.73 g/g of creatininuria, hematuria, and acute kidney injury needing dialysis associated with lung hemorrhage; anti-neutrophil cytoplasmic antibody (ANCA titer ≥1,280 with myeloperoxidase specificity of 780 U/mL) was positive, and kidney biopsy confirmed glomerular injury with crescents. The patient underwent treatment with steroid pulses, rituximab, and plasmapheresis, resulting in an improvement of the renal function and lung hemorrhage and produced a negative ANCA titer. Despite the results of the PEXIVAS study and the absence of clear benefit of plasmapheresis demonstrated in idiopathic AAV, we suggest that drug-induced AAV may be effectively treated by plasmapheresis, steroids, and rituximab.

Protocol Biopsies on de novo Renal-Transplants at 3 Months after Surgery: Impact on 5-Year Transplant Survival.

BACKGROUND: In many centers, a protocol kidney biopsy (PKB) is performed at 3 months post-transplantation (M3), without a demonstrated benefit on death-censored graft survival (DCGS). In this study, we compared DCGS between kidney transplant recipients undergoing a PKB or without such biopsy while accounting for the obvious indication bias. METHODS: In this retrospective, single-center study conducted between 2007 and 2013, we compared DCGS with respect to the availability and features of a PKB. We built a propensity score (PS) to account for PKB indication likelihood and adjusted the DCGS analysis on PKB availability and the PS. RESULTS: A total of 615 patients were included: 333 had a PKB, 282 did not. In bivariate Kaplan-Meier survival analysis, adjusting for the availability of a PKB and for the PS, a PKB was associated with a better 5-year DCGS independently of the PS (p < 0.001). Among the PKB+ patients, 87 recipients (26%) had IF/TA > 0. Patients with an IF/TA score of 3 had the worst survival. A total of 144 patients (44%) showed cv lesions. Patients with cv2 and cv3 lesions had the worst 5-year DCGS. CONCLUSIONS: A M3 PKB was associated with improved graft survival independently of potential confounders. These results could be explained by the early treatment of subclinical immunological events. It could be due to better management of the immunosuppressive regimen.

A Case of Pneumocystis jirovecii Pneumonia under Belatacept and Everolimus: Benefit-Risk Balance between Renal Allograft Function and Infection.

Pneumocystis jirovecii pneumonia is an opportunistic disease usually prevented by trimethoprim-sulfamethoxazole. A 49-year-old HLA-sensitized male with successful late conversion from tacrolimus-based to belatacept-based immunosuppression developed P. jirovecii pneumonia for which he presented several risks factors: low lymphocyte count with no CD4+ T cells detected since 2 years, hypogammaglobulinemia, history of acute cellular rejection 3 years before, and immunosuppressive treatment (belatacept, everolimus). Because of respiratory gravity in the acute phase, the patient was given oxygen, corticosteroids, and trimethoprim-sulfamethoxazole. Thanks to the improvement of respiratory status, and because of the renal impairment, trimethoprim-sulfamethoxazole was converted to atovaquone for 21 days. Indeed, after 1 week on intensive treatment, the benefit-risk balance favored preserving renal function according to respiratory improvement status. P. jirovecii pneumonia prophylaxis for the next 6 months was monthly aerosol of pentamidine. Long-term safety studies or early/late conversion to belatacept did not report on P. jirovecii pneumonia. Four other cases of P. jirovecii pneumonia under belatacept therapy were previously described in patients having no P. jirovecii pneumonia prophylaxis. Studies on the reintroduction of P. jiroveciipneumonia prophylaxis after conversion to belatacept would be of interest. It could be useful to continue regular evaluation within the second-year post-transplantation regarding immunosuppression: T-cell subsets and immunoglobulin G levels.

Impact of Immunosuppressive Strategies on Post-Kidney Transplantation Thrombocytopenia.

BACKGROUND: Thrombocytopenia after kidney transplantation is a common complication, partly induced by immunosuppressive therapies. Peritransplant thrombocytopenia may cause serious hemorrhages. We assessed the incidence of early posttransplantation thrombocytopenia (defined as a platelet count of <150,000 mm3 or <150 G/L) in de novo kidney transplant recipients (KTRs) across 4 immunosuppressive regimens. METHODS: This was a single-center observational study that included all consecutive KTRs who received either Thymoglobulin (THY) or Grafalon (GRA) and maintenance therapy of either mycophenolate-mofetil (MMF) or everolimus (EVR), associated with tacrolimus/corticosteroids. RESULTS: Between July 27, 2016, and September 7, 2018, 237 KTRs were included; 64.6% experienced thrombocytopenia within the first week. Thrombocytopenia was significantly more frequent (P = .004) among GRA-treated patients (73.4%) compared to THY-treated patients (61.3%). These patients also had lower nadir platelet count (120 ± 52 vs 142 ± 48 G/L; P = .002) and lower platelet count at discharge (227 ± 94 vs 243 ± 92 G/L; P = .25). More of the GRA-EVR group had thrombocytopenia (81.0% vs 61.4% in THY-MMF, 60.9% in THY-EVR, and 69.8% in GRA-MMF; P = .081) and a worse nadir platelet count (109 ± 41 in GRA-EVR vs 141 ± 47G/L in THY-MMF, 145 ± 52 G/L in THY-EVR, and 125 ± 56 G/L in GRA-MMF; P = .011) but GRA was the only risk factor for thrombocytopenia in multivariate analyses (P = .002). Rates of hemorrhage, red blood cell transfusions, reoperations needed within the first week, delayed graft function, acute rejection, graft loss, and death did not differ between the groups after a mean follow-up of 25 ± 8 months. CONCLUSIONS: GRA associated with EVR led to more frequent and severe thrombocytopenia, although we found no significant clinical consequences.

Apheresis Efficacy and Tolerance in the Setting of HLA-Incompatible Kidney Transplantation.

Nearly 18% of patients on a waiting list for kidney transplantation (KT) are highly sensitized, which make access to KT more difficult. We assessed the efficacy and tolerance of different techniques (plasma exchanges [PE], double-filtration plasmapheresis [DFPP], and immunoadsorption [IA]) to remove donor specific antibodies (DSA) in the setting of HLA-incompatible (HLAi) KT. All patients that underwent apheresis for HLAi KT within a single center were included. Intra-session and inter-session Mean Fluorescence Intensity (MFI) decrease in DSA, clinical and biological tolerances were assessed. A total of 881 sessions were performed for 45 patients: 107 DFPP, 54 PE, 720 IA. The procedures led to HLAi KT in 39 patients (87%) after 29 (15-51) days. A higher volume of treated plasma was associated with a greater decrease of inter-session class I and II DSA (p = 0.04, p = 0.02). IA, PE, and a lower maximal DSA MFI were associated with a greater decrease in intra-session class II DSA (p < 0.01). Safety was good: severe adverse events occurred in 17 sessions (1.9%), more frequently with DFPP (6.5%) p < 0.01. Hypotension occurred in 154 sessions (17.5%), more frequently with DFPP (p < 0.01). Apheresis is well tolerated (IA and PE > DFPP) and effective at removing HLA antibodies and allows HLAi KT for sensitized patients.

Early Steroid Withdrawal After Kidney Transplantation in Patients at Risk for New-Onset Diabetes After Transplantation.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation because of worse graft survival and increased risk of cardiovascular events. It is partly induced by immunosuppressive therapies such as corticosteroids. This study aimed to assess whether early corticosteroid withdrawal on day 4 (early steroid withdrawal [ESW] group) could prevent the development of NODAT within 2 years posttransplantation while maintaining good graft and patient survival rates. METHODS: This was an observational, single-center, retrospective study. All patients received an induction therapy of antithymocyte globulin or basiliximab and maintenance therapy of tacrolimus/mycophenolate mofetil/corticosteroids. Patients were either weaned off corticosteroids on day 4 (ESW group) or were maintained on corticosteroids for at least 3 months (standard group). NODAT was defined as the initiation of any oral hypoglycemic agent or insulin at 3 months and up to 2 years posttransplantation in previously nondiabetic recipients. RESULTS: Between January, 1, 2010, and December 14, 2014, 492 recipients were included in this study; 88 received the ESW strategy, and 404 received the standard strategy. Age and body mass index (BMI) were significantly higher in the ESW group. The incidence of NODAT was 36.8% in the ESW group and 8.8% in the standard group (odds ratio [OR], 47.5; P < .001). Compared with a matched sample from the standard group that had the same probability to benefit from ESW at baseline, ESW was still associated with a significantly increased risk of NODAT (OR, 4.41; P = .018). Among recipients with a BMI >25 kg/m2, the ESW strategy significantly decreased the risk of NODAT compared with the standard strategy (OR, 0.07; P = .013). Safety endpoints (eg, acute rejection, de novo-specific antibodies, graft function/survival) did not differ between groups. CONCLUSION: Despite a reassuring safety profile, ESW on day 4 after kidney transplantation only had a marginal effect on the incidence of NODAT.

Cytomegalovirus disease in de novo kidney-transplant recipients: comparison of everolimus-based immunosuppression without prophylaxis with mycophenolic acid-based immunosuppression with prophylaxis.

PURPOSE: To compare everolimus (EVR) plus low-dose tacrolimus (TAC) with mycophenolic acid (MPA) plus standard-dose TAC with regards to rates of cytomegalovirus (CMV) disease in de novo kidney-transplant recipients (KTRs). METHODS: This single-center retrospective study included 187 de novo KTRs; 59 patients (31.6%) received EVR/low-dose TAC (group 1); 128 patients (68.4%) received MPA with standard-dose TAC (group 2). All received anti-thymocyte globulins as the induction therapy, and steroid-sparing strategy. Valganciclovir prophylaxis was mandatory for CMV D+/R- KTRs (seronegative recipients of a seropositive donor) in both groups and for R+ seropositive recipients (only in group 2). RESULTS: The 2-year incidence of CMV disease was low and comparable between groups: 6.8% and 7.0% in groups 1 and 2, respectively (p = 0.94). There was no statistical difference in CMV serostatus (p = 1). However, CMV disease tended to be less frequent, though not statistically different, in R+ KTRs receiving EVR without prophylaxis (3.7% vs. 8.5% in groups 1 and 2, respectively) and in patients without EVR discontinuation (2.6% vs. 6.9% in patients who did not discontinue MPA (p = 0.29). Two-year graft function was good and comparable between groups (median eGFR of 54.2 and 53.0 mL/min in groups 1 and 2, respectively; p = 0.47); incidence of immunological events was low. Significantly more patients in group 1 discontinued EVR because of adverse events than patients that discontinued MPA in group 2 (35.6% in group 1 vs. 10.2% in group 2; p < 0.001). CONCLUSIONS: Everolimus plus low-dose TAC given to de novo KTRs was associated with low rates of CMV disease, especially in R+ patients with no CMV prophylaxis.

Late Conversion From Calcineurin Inhibitors to Belatacept in Kidney-Transplant Recipients Has a Significant Beneficial Impact on Glycemic Parameters.

BACKGROUND: Calcineurin inhibitors (CNIs) and steroids are strongly associated with new-onset diabetes after transplantation, worsening of pre-existing diabetes, and cardiovascular events. We assessed the benefit of conversion from CNI-based to belatacept-based immunosuppression in diabetic kidney-transplant (KT) recipients on glucose control and cardiovascular risk factors. METHODS: In this retrospective, noncontrolled single-study conducted between May 2016 and October 26, 2018, we recruited KT recipients converted from CNIs to belatacept at least 6 months after KT. The primary endpoint was the evolution of hemoglobin A1c (HbA1c) between baseline and after 6 months of treatment. Secondary endpoints included modifications to antidiabetic drugs, other cardiovascular risk factors, and renal function. RESULTS: One hundred and three KT recipients were included. Of these, 26 (25%) had type 2 diabetes. The patients were either receiving oral antidiabetic drugs (n = 21; 75%) or insulin therapy (n = 14; 54%). Overall HbA1c decreased significantly from 6.2 ± 1 to 5.8 ± 1%, P < 0.001. In diabetic patients, HbA1c decreased from 7.2 ± 1 to 6.5 ± 1%, P = 0.001. HbA1c significantly decreased in the subgroup of patients with new-onset diabetes after transplantation and whether diabetes was controlled at inclusion or not (ie, HA1c ≤7% or >7%). Moreover, no diabetic patient increased the number of oral antidiabetic drugs and the dose of basal insulin was not statistically different from baseline to 6 months (16 international unit at baseline and 16 international unit at 6 mo, P = 1). One patient had to start treatment by insulin pump. During follow-up, the renal function, body mass index, and hemoglobin level of all 103 patients remained stable, 2 patients presented acute cellular rejection, and no patient suffered from graft loss. CONCLUSIONS: A late switch from CNI to belatacept was a valuable therapeutic option for diabetic kidney recipients and substantially improved glycemic parameters.

Opportunistic Infections and Efficacy Following Conversion to Belatacept-Based Therapy after Kidney Transplantation: A French Multicenter Cohort.

Conversion from calcineurin-inhibitors (CNIs) to belatacept can help kidney-transplant (KT) recipients avoid CNI-related nephrotoxicity. The risk of associated opportunistic infections (OPIs) is ill-defined. We conducted a multicentric cohort study across 15 French KT-centers in a real-life setting. Between 07-2010 and 07-2019, 453 KT recipients were converted from CNI- to belatacept-based therapy at 19 [0.13-431] months post-transplantation. Most patients, i.e., 332 (79.3%), were converted after 6-months post-transplantation. Follow-up time after conversion was 20.1 +/- 13 months. OPIs developed in 42(9.3%) patients after 14 +/- 12 months post-conversion. Eight patients (19%) had two OPI episodes during follow-up. Incidences of CMV DNAemia and CMV disease were significantly higher in patients converted before 6-months post-KT compared to those converted later (i.e., 31.6% vs. 11.5%; p < 0.001; and 11.6% vs. 2.4%, p < 0.001, respectively). Cumulative incidence of OPIs was 6.5 OPIs/100 person-years. Incidence of CMV disease was 2.8/100 person-years, of pneumocystis pneumonia 1.6/100 person-years, and of aspergillosis 0.2/100 person-years. Multivariate analyses showed that estimated glomerular filtration (eGFR) < 25 mL/min/1.73 m2 at conversion was independently associated with OPIs (HR = 4.7 (2.2 - 10.3), p < 0.001). The incidence of EBV DNAemia was 17.3 events /100 person-years. At 1-year post-conversion, mean eGFR had significantly increased from 32.0 +/- 18 mL/min/1.73 m2 to 42.2 +/- 18 mL/min/1.73 m2 (p < 0.0001). Conversion to belatacept is an effective strategy with a low infectious risk.