Is There a Place for Apheresis in the Management of Idiopathic Membranous Nephropathy? A Report of Three Cases and Literature Review.

Membranous nephropathy constitutes approximately 20% of adult nephrotic syndrome cases. In approximately 80% of cases, membranous nephropathy is primary, mediated by IgG autoantibodies primarily targeting podocyte antigens (PLA2R, THSD7A, etc.). The treatment involves a combination of corticosteroids and cyclophosphamide or anti-CD20-based therapies, e.g., rituximab. In the event of significant proteinuria and in order to avoid the urinary elimination of rituximab, therapeutic apheresis, in particular semi-specific immunoadsorption, may be an option allowing for a reduction in proteinuria and autoantibodies before initiating treatment with rituximab. We present the preliminary experience of three patients treated with semi-specific immunoadsorption for primary membranous nephropathy between January 2021 and March 2023. Two patients were anti-PLA2R-autoantibody-positive and one was seronegative. The average age was 59 ± 17 years. Semi-specific immunoadsorption did not reduce albuminuria, but it, nevertheless, led to an increase in serum albumin, contributing to the regression of edema. It effectively eliminated anti-PLA2R autoantibodies in the two anti-PLA2R-positive patients. Consequently, apheresis may not induce a rapid reduction in proteinuria, but could contribute to a more accelerated remission when combined with the anti-CD20 treatment.

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.

Early Blood Transfusion After Kidney Transplantation Does Not Lead to dnDSA Development: The BloodIm Study.

Outcomes after kidney transplantation are largely driven by the development of de novo donor-specific antibodies (dnDSA), which may be triggered by blood transfusion. In this single-center study, we investigated the link between early blood transfusion and dnDSA development in a mainly anti-thymocyte globulin (ATG)-induced kidney-transplant cohort. We retrospectively included all recipients of a kidney transplant performed between 2004 and 2015, provided they had >3 months graft survival. DSA screening was evaluated with a Luminex assay (Immucor). Early blood transfusion (EBT) was defined as the transfusion of at least one red blood-cell unit over the first 3 months post-transplantation, with an exhaustive report of transfusion. Patients received either anti-thymocyte globulins (ATG) or basiliximab induction, plus tacrolimus and mycophenolic acid maintenance immunosuppression. A total of 1088 patients received a transplant between 2004 and 2015 in our center, of which 981 satisfied our inclusion criteria. EBT was required for 292 patients (29.7%). Most patients received ATG induction (86.1%); the others received basiliximab induction (13.4%). dnDSA-free graft survival (dnDSA-GS) at 1-year post-transplantation was similar between EBT+ (2.4%) and EBT- (3.0%) patients (chi-squared p=0.73). There was no significant association between EBT and dnDSA-GS (univariate Cox's regression, HR=0.88, p=0.556). In multivariate Cox's regression, adjusting for potential confounders (showing a univariate association with dnDSA development), early transfusion remained not associated with dnDSA-GS (HR 0.76, p=0.449). However, dnDSA-GS was associated with pretransplantation HLA sensitization (HR=2.25, p=0.004), hemoglobin >10 g/dL (HR=0.39, p=0.029) and the number of HLA mismatches (HR=1.26, p=0.05). Recipient's age, tacrolimus and mycophenolic-acid exposures, and graft rank were not associated with dnDSA-GS. Early blood transfusion did not induce dnDSAs in our cohort of ATG-induced patients, but low hemoglobin level was associated with dnDSAs-GS. This suggests a protective effect of ATG induction therapy on preventing dnDSA development at an initial stage post-transplantation.

Very Early Severe Posttransplant Recurrent Antineutrophil Cytoplasmic Antibody-Associated Glomerulonephritis after Kidney Transplantation: Two Case Reports.

Successful kidney transplantation (KTx) in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV) has been reported with excellent patient and graft survival rates. The recurrence of AAV in transplant recipients is rare, and its mechanisms of action are not clearly known. The optimum time for KTx and the relevance of ANCA titer at the time of transplantation remain controversial. We report two cases of extremely rapid recurrent AAV after renal transplantation; both were still ANCA-positive at the time of transplantation, which led us to question the pathogenesis of ANCA antibodies in recurrence in a kidney allograft. Apheresis plus immunosuppressive therapies were ineffective in the first case and the patient became dialysis-dependent, whereas in the second case methylprednisone pulses plus rituximab infusions resulted in long-lasting remission.

Immune responses following tocilizumab therapy to desensitize HLA-sensitized kidney transplant candidates.

Kidney transplant candidates (KTCs) who are HLA highly sensitized (calculated panel-reactive alloantibodies >95%) have poor access to deceased kidney transplantation. In this single-center prospective study, 13 highly sensitized desensitization-naïve KTCs received IV tocilizumab (8 mg/kg) every 4 weeks. We evaluated tolerability as well as immune responses, that is, T cell, B cell, T follicular helper (Tfh) subsets, blood cytokines (IL-6, soluble IL-6 receptor-sIL-6R-, IL-21), blood chemokines (CXCL10, CXCL13), and anti-HLA alloantibodies. Tocilizumab treatment was well-tolerated except in one patient who presented spondylodiscitis, raising a note of caution. Regarding immune parameters, there were no significant changes of percentages of lymphocyte subsets, that is, CD3+ , CD3+ /CD4+ , CD3+ /CD8+ T cells, and NK cells. This was also the case for Tfh cell subsets, B cells, mature B cells, plasma cells, pre-germinal center (GC) B cells, and post-GC B cells, whereas we observed a significant increase in naïve B cells (p = .02) and a significant decrease in plasmablasts (p = .046) over the tocilizumab treatment course. CXCL10, CXCL13, IL-21, total IgG, IgA, and IgM levels did not significantly change during tocilizumab therapy; conversely, there was a significant increase in IL-6 levels (p = .03) and a huge increase in sIL-6R (p = .00004). There was a marginal effect on anti-HLA alloantibodies (class I and class II). To conclude in highly sensitized KTCs, tocilizumab as a monotherapy limited B cell maturation; however, it had almost no effect on anti-HLA alloantibodies.

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.,

Immortal Time-Bias-Corrected Survival of Highly Sensitized Patients and HLA-desensitized Kidney Transplant Recipients.

INTRODUCTION: In the setting of kidney transplantation (KT), we assessed the efficacy of desensitization and compared the survival of desensitized patients (HLA-incompatible KT) with similarly sensitized patients receiving HLA-compatible KT or sensitized patients still on a waiting list after adjusting for the usually unaccounted immortal time bias. METHODS: All patients in a French KT center on the waiting list between August 1994 and December 2019 with a high level of sensitization (panel-reactive antibodies [PRAs] ≥80%) were included. The primary outcome was all-cause mortality. A time-varying covariate Cox survival model was used to account for the immortal time bias. A landmark analysis was used as a sensitivity analysis. RESULTS: During the study period, 326 patients with high PRAs were followed, among which 147 (45%) remained on the waiting list at the time of last follow-up and 179 benefited from a KT. Thirty-six patients were desensitized, of which 30 received a kidney transplant, including eight deceased kidney donors. There were no differences in mortality rates between desensitized KT patients, nondesensitized KT patients, and waitlisted patients after adjusting for immortal time bias (hazard ratio [HR] = 0.48, P = 0.22). Death-censored graft survival was similar between desensitized and nondesensitized KT patients (HR = 0.92, P = 0.88 adjusting for donor age >65 years, donor status, and time on the waiting list). Mean estimated glomerular filtration rate at 1 year post-KT was similar for desensitized KT patients (53.3 ± 21 vs. 53.6 ± 21 ml/min per 1.73 m2 for nondesensitized patients; P = 0.95). CONCLUSIONS: HLA-desensitization was effective for highly sensitized patients and gave access to KT without detrimental effects on patient or graft survival rates.

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.

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.

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.

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.

Marginal Impact of Tocilizumab Monotherapy on Anti-HLA Alloantibodies in Highly Sensitized Kidney Transplant Candidates.

BACKGROUND: Highly HLA-sensitized kidney transplant candidates are difficult to desensitize, which reduces their chances of receiving a transplant. METHODS: We administered tocilizumab as a monotherapy (8 mg/kg once a mo) to 14 highly sensitized kidney transplant candidates. Highest mean fluorescence intensities of anti-HLA antibodies obtained before and after tocilizumab administration were compared from raw and diluted sera. RESULTS: The administration of tocilizumab significantly reduced dominant anti-HLA antibody sensitization. However, this decrease in mean fluorescence intensities was minor compared with the initial values. CONCLUSIONS: Tocilizumab as a monotherapy was not sufficient to allow highly sensitized kidney-transplant candidates to undergo transplantation and, therefore, was not an effective desensitization method.

Fibrinogen reconstitution after therapeutic apheresis: Comparison of double-filtration plasmapheresis, plasma exchange, and immunoadsorption.

BACKGROUND: Fibrinogen reconstitution after therapeutic apheresis has been poorly studied. Apheresis modalities, for example, plasma exchange (PE), double-filtration plasmapheresis (DFPP), or selective immunoadsorption (IA), may have different impacts. METHODS: We retrospectively investigated therapeutic apheresis sessions performed at our center across four modalities (PE, DFPP, and IA with or without plasma filtration). Fibrinogen levels were assessed at the beginning and end of each apheresis session, and immediately before the subsequent session. We adjusted measurements on hematocrit values to account for hemoconcentration. RESULTS: Between January 10, 2016 and March 2, 2020, we included 90 patients for a total of 754 apheresis sessions (PE: 35; DFPP: 351; IA only: 109; IA + plasma filtration: 259). Each patient received a median of five sessions (1Q 3; 3Q 9); median plasma volume treated was 5.5 L (1Q 4.3 L; 3Q 7.0 L). Within a session, DFPP and PE induced a significantly greater depletion of fibrinogen than both IA modalities, even after adjustment for the treated plasma volume. Median fibrinogen reconstitution was 0.8 (0.4-1.2) g/L (median time between sessions: 38 hours). In multivariate analysis, fibrinogen reconstitution was significantly associated with intersession time (+0.66 g/L/log-hour P < .001), apheresis modality (ANOVA; P < .001), initial fibrinogen concentration (+0.15 g/L per gram of fibrinogen; P < .001), and the last fibrinogen concentration from the previous apheresis session (-0.14 g/L per gram of fibrinogen; P < .001). In a model that considered hemoconcentration, the results were unchanged. CONCLUSIONS: We demonstrate that fibrinogen reconstitution was highly variable between patients and apheresis sessions. Apheresis modalities had a significant impact on fibrinogen reconstitution, regardless of hemoconcentration.

Treatment of antibody-mediated rejection with double-filtration plasmapheresis, low dose IVIg plus rituximab after kidney transplantation.

Antibody-mediated rejection (ABMR) at early or late post-transplantation remains challenging. We performed a single-center single-arm study where four cases of acute ABMR and nine cases of chronic active ABMR (defined by Banff classification) were treated with double-filtration plasmapheresis (two cycles of three consecutive daily sessions with a 4-day gap between). At the end of the third and sixth DFPP sessions, the patients received rituximab 375 mg/m2 . After a median follow-up of 1078 (61-1676) days, kidney-allograft survival was 50%. Before DFPP/rituximab therapy, the median donor-specific alloantibody (DSA) mean fluorescence intensity (MFI) was 9160 (4000-15 400); 45 days (D45) later it had significantly decreased to 7375 (215-18 100) (P = .018). In addition, at one-year (Y1) post-therapy, MFI had decreased further, that is, 4060 (400-7850) (P = .001). In two patients, DSA MFIs decreased and remained below 2000. The slope of estimated glomerular-filtration rate within the 6 months preceding intervention was -1.18 mL/min/month and remained unchanged at -1.29 mL/min/month within the year after intervention. Proteinuria remained unchanged. Baseline Banff scores on repeat allograft biopsies (post-therapy D45, Y1) did not show any improvement. Side-effects were mild to moderate. We conclude that the combined DFPP/rituximab significantly decreased DSAs in ABMR kidney-transplant recipients but did not improve renal function or renal histology at 1-year follow-up.

Comparison of three modalities of plasmapheresis on coagulation: Centrifugal, single-membrane filtration, and double-filtration plasmapheresis.

BACKGROUND: Plasmapheresis can deplete pathogenic antibodies and allow ABO- and/or HLA-incompatible transplantation. AIM: To determine the impacts of three modalities of plasmapheresis (centrifugal plasmapheresis [cTPE], single-filtration plasmapheresis [mTPE], double-filtration plasmapheresis [DFPP]) on hemostasis parameters and thrombin generation. MATERIALS/METHODS: Prospective, comparative study on 21 patients that received three modalities of plasmapheresis (7 patients/group). Hemostasis (prothrombin time [PT], activated partial thromboplastin time [aPTT], procoagulant factors and natural anticoagulants) were measured before and after the first plasmapheresis session. Thrombin generation was also assessed in platelet-poor plasma using an STA-Genesia (Stago) analyzer and Thromboscreen reagents (Stago) in 4-5 patients from each group. RESULTS: Both cTPE and mTPE resulted in high decreases in proteins, whatever their molecular weights. Median post/pre ratios were 0.27 to 0.55 for cTPE for most proteins (except FVIII [0.64] and VWF [0.57]). Median post/pre-ratios of mTPE were 0.28 to 0.56 for all proteins. DFPP decreased high-molecular-weight proteins (fibrinogen, FV, FVIII, FXI, VWF) and proteins strongly bound to large molecules (protein SandTFPI). Median post/pre ratios with cTPE and mTPE were similar to DFPP for fibrinogen and FXIII. Regarding thrombin generation, cTPE and mTPE did not significantly modify endogenous thrombin potential (ETP) and DFPP induced a slight decrease in ETP (median post/pre ratio at 0.73) in the absence of thrombomodulin. ETP inhibition by thrombomodulin was decreased for all procedures. CONCLUSIONS: DFPP depleted high molecular-weight proteins in contrast to cTPE and mTPE, which significantly decreased all proteins. Regarding thrombin generation, depletion of procoagulant factors was counterbalanced by a decrease in some natural anticoagulants whatever plasmapheresis method used; with all methods, fibrinogen and FXIII were highly depleted.

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.

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.

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.

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.

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.