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Objectives Most data on glomerular filtration rate (GFR) originate from subjects Methods mGFR percentiles were calculated from a development cohort of French/Belgian living kidney donors Results Individuals in the development cohort had a higher mGFR (99.9 ± 16.4 vs. 86.4 ± 14 and 82.7 ± 15.5 mL/min/1.73 m2) compared to the individuals in the validation cohorts. In the internal validation cohort, none (0%) had mGFR below the extrapolated P5, 12 (8.2%) above P95 and 135 (91.8%) between P5–P95. In the external validation cohort, five subjects had mGFR below the extrapolated P5 (1.5%), 25 above P95 (7.6%) and 299 (90.9%) between P5–P95. Conclusions We demonstrate that extrapolation of mGFR from younger donors is possible and might aid with decision-making in elderly donors.

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-naive 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 naive 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.

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.

International audience; Multiple days assessments are frequent for the evaluation of candidates to living kidney donation, combined with an early GFR estimation (eGFR). Living kidney donation is questionable when eGFR is 55 years) in a population of 1825 French living kidney donors with a median follow-up of 5.9 years. In donors younger than 45, postdonation eGFR, absolute- and relative-eGFR variation were not different between the three groups. For older donors, postdonation eGFR was higher in S90 than in S80 or Sage but other comparators were identical. Postdonation eGFR slope was comparable between all groups. Our results are in favour of in-depth screening for all candidates to donation with a normal eGFR for age.

Thrombotic microangiopathy (TMA) is most of the time caused by thrombotic thrombocytopenic purpura or hemolytic uremic syndrome. A 60-year-old female was diagnosed in 2014 with mammary breast adenocarcinoma treated by several-line therapy: mastectomy, docetaxel, cyclophosphamide, radiotherapy, doxorubicine, and capecitabine. By mid-November, the patient was admitted to the hospital with regenerative, mechanical, and hemolytic anemia, schistocytes at 3%, and thrombopenia (99 G/L), associated with high blood transfusion requirement. After 9 sessions of plasmapheresis, there was no significant improvement in the biological parameters, nor after 2 cycles of paclitaxel. The patient was then treated with eculizumab during 4 weeks, with a slight reduction in blood requirement, and simultaneously with palbociclib. Since being treated with palpociclib, she had a great reduction in blood requirement and a good clinical condition. To conclude, we reported an initial moderate improvement of paraneoplasm-related TMA syndrome under eculizumab therapy with a slight reduction in red blood cell requirement; however, palbociclib therapy achieved a very good response with a dramatic reduction in red blood cell requirement.

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

Background The Chronic Kidney Disease in Children Study (CKiD) equation for children and the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for adults are recommended serum creatinine (SCr)-based calculations for estimating glomerular filtration rate (GFR). However, these equations, as well as their combination, have limitations, notably the problem of implausible changes in GFR during the transition from adolescence to adulthood and overestimation of GFR in young adults. The full age spectrum (FAS) equation addresses these issues but overestimates GFR when SCr levels are low. Objective To develop and validate a modified FAS SCr-based equation combining design features of the FAS and CKD-EPI equations. Design Cross-sectional analysis with separate pooled data sets for development and validation. Setting Research and clinical studies (n = 13) with measured GFR available. Patients 11 251 participants in 7 studies (development and internal validation data sets) and 8378 participants in 6 studies (external validation data set). Measurements Clearance of an exogenous marker (reference method), SCr level, age, sex, and height were used to develop a new equation to estimate GFR. Results The new European Kidney Function Consortium (EKFC) equation is a FAS equation with low bias (-1.2 mL/min/1.73 m2 [95% CI, -2.7 to 0.0 mL/min/1.73 m2] in children and -0.9 mL/min/1.73 m2 [CI, -1.2 to -0.5 mL/min/1.73 m2] in adults) across the FAS (2 to 90 years) and SCr range (40 to 490 µmol/L [0.45 to 5.54 mg/dL]) and with fewer estimation errors exceeding 30% (6.5% [CI, 3.8% to 9.1%] in children and 3.1% [CI, 2.5% to 3.6%] in adults) compared with the CKiD and CKD-EPI equations. Limitation No Black patients were included. Conclusion The new EKFC equation shows improved accuracy and precision compared with commonly used equations for estimating GFR from SCr levels. Primary funding source Swedish Research Council (Vetenskapsradet).

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.

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.

Introduction Myasthenia gravis (MG) is an autoimmune disease mediated by circulating autoantibodies (anti-AchR, anti-MuSK, etc.). More than 20% of myasthenic patients are refractory to conventional treatments (plasma exchange, IVIg, steroids, azathioprine, mycophenolate mofetil). Rituximab (B-lymphocyte-depleting anti-CD20) and apheresis (double-filtration plasmapheresis [DFPP] and immunoadsorption [IA]) are interesting therapeutic alternatives. Methods This monocentric pilot study included nine refractory myasthenic patients (March 2018 to May 2020) treated by DFPP and/or IA associated with rituximab (375 mg/m2 ). Clinical responses were assessed using the Myasthenia Gravis Foundation of America (MGFA) score. Results Average age of patients was 53 ± 17 years. Gender ratio (M/F) was 3:6. The combination of apheresis and rituximab reduced median MGFA score from IV to II after 12 months of follow-up. Clinical improvement assessed by MGFA score was sustained in the long-term for all patients, during an average follow-up of 14 ± 9 months, allowing them to be self-sufficient and out sick-leave. The median number of apheresis sessions was 7 (5-30). The dose of prednisolone was reduced in two patients from 40 mg/d and 30 mg/d to 7.5 mg/d and 10 mg/d, respectively. It was stopped in a patient who was taking 30 mg/d. No infectious, bleeding, or thrombosis complications were noted. Conclusion The combination of rituximab and DFPP was effective to treat refractory MG.

Preexisting diabetes (PD) and post-transplant diabetes mellitus (PTDM) are common and severe comorbidities posttransplantation. The immunosuppressive regimens are modifiable risk factors.We reviewed Pubmed and Cochrane database and we summarize the mechanisms and impacts of available immunosuppressive treatments on the risk of PD and PTDM. We also assess the possible management of these drugs to improve glycemic parameters while considering risks inherent in transplantation.PD i) increases the risk of sepsis, ii) is an independent risk factor for infection-related mortality, and iii) increases acute rejection risk. Regarding PTDM development i) immunosuppressive strategies without corticosteroids significantly reduce the risk but the price may be a higher incidence of rejection; ii) minimization or rapid withdrawal of steroids are two valuable approaches; iii) the diabetogenic role of calcineurin inhibitors(CNIs) is also well-described and is more important for tacrolimus than for cyclosporine. Reducing tacrolimus-exposure may improve glycemic parameters but also has a higher risk of rejection. PTDM risk is higher in patients that receive sirolimus compared to mycophenolate mofetil. Finally, conversion from CNIs to belatacept may offer the best benefits to PTDM-recipients in terms of glycemic parameters, graft and patient-outcomes.

Kidney transplant recipients (KTRs) are frequently infected with chronic hepatitis C virus (HCV), which can increase the risk of graft loss. Active HCV infections among KTRs are associated with shorter survival times. The emergence of very efficient interferon-free treatments (direct-acting antivirals [DAAs]) has revolutionized prognoses for chronic viral hepatitis. We performed a multicenter study where HCV (+)/RNA (+) KTRs were followed up and either received DAAs (group A) or not (group B) according to the transplant center. The aim was to assess, in a real-life setting, the impact of DAA therapy and to compare these results with those from HCV RNA (+) KTRs where HCV infection was not treated during the same period.This study included 66 patients from 11 centers: 44 patients (66.7%; group A) received DAAs, whereas 22 patients did not (group B); the 2 groups were comparable according to baseline data. Most patients (88.6%) received sofosbuvir, 50% received ledipasvir, and 34.7% received daclatasvir. The duration of treatments ranged from 8 to 24 weeks.HCV RNA clearance (ie, a sustained virologic response) was observed in 95.4% of treated patients. Eradication of HCV led to a significant decrease in liver enzymes (50% reduction for alanine aminotransferase [P ≤ .001] and 41% for gamma glutamyl transpeptidase [P .001]). Conversely, liver enzymes did not decrease in group B. Death occurred significantly more frequently in nontreated than treated patients (3 in group B vs none in group A, P = .003). Of the 10 treated patients with severe renal impairment before DAA therapy, 6 experienced graft loss.DAAs are very effective at treating chronic HCV and have an excellent tolerance profile.

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.

Living donor nephrectomy is a high-stake procedure involving healthy individuals, therefore every effort should be made to define each patient’s individualized risk and improve potential donors’ information. The aim of this study was to evaluate the interest of the Mayo adhesive probability (MAP) score, an imaging-based score initially designed to estimate the risk of adherent perinephric fat in partial nephrectomy, to predict intra- and postoperative complications of living donor nephrectomy. We retrospectively reviewed the imaging, clinical, and follow-up data of 452 kidney donors who underwent laparoscopic donor nephrectomy in two academic centers. Imaging and follow-up data were available for 307 kidney donors, among which 44 (14%) had a high MAP score (≥ 3). Intraoperative difficulties were encountered in 50 patients (16%), including difficult dissection (n = 35) and bleeding (n = 17). Conversion to open surgery was required for 13 patients (4.2%). On multivariate analysis, a MAP score ≥ 3 was significantly associated with the risk of intraoperative difficulty [OR 14.12 (5.58–35.7), p

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). 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). 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

INTRODUCTION ABO- or HLA-incompatible kidney transplantation is possible thanks to pretransplant antibody-depletion achieved by extracorporeal-treatment modalities. These methods induce depletion of some plasma proteins and may also impact on proteins involved in hemostasis. METHODS To determine the impact of one session of immunoadsorption (IA) alone or combined with membrane filtration (MF) on clotting factors and natural anticoagulants, we performed a prospective, observational study on 13 patients waiting for HLA-/ABO-incompatible kidney transplants. Plasma hemostasis parameters were measured before and immediately after a first session of IA alone in six patients and of IA + MF in seven patients. RESULTS IA alone induced depletion of fibrinogen and factor XIII (FXIII) whereas IA + MF caused greater depletion of all high-molecular-weight hemostatic proteins (fibrinogen, FV, FVIII, FXI, FXIII, von-Willebrand factor [VWF]). After an IA session, median reductions were 30% for fibrinogen and 43% for FXIII compared to baseline values. After a session of IA + MF, median decreases were 70% for fibrinogen, 54% for FV, 56% for FVIII, 37% for FXI, 78% for FXIII, and 62% for VWF. Noticeably, levels of low-molecular-weight factors (

This is the peer reviewed version of the following article: Delanaye, P., Björk, J., Courbebaisse, M., Couzi, L., Ebert, N., Eriksen, B.O., .... Nyman, U. (2021). Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment. British Journal of Clinical Pharmacology, which has been published in final form at https://doi.org/10.1111/bcp.15132. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited. Aim: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing. Methods: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR) and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR Results: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR 2, all equations performed similarly, and for BMI 2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2). The four more recent equations also classified mGFR stages better than CG. Conclusions: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.

Background This study aimed to identify transplantation characteristics and biomarkers that predict outcomes for kidney transplant (KT) patients from donors after circulatory death (DCDs). Methods Consecutive patients receiving a KT from a DCD in our center between 2014 and 2016 were included; the reference population was recipients with a living donor KT. The urinary tubular injury biomarker-to-creatinine ratio and serum lactate dehydrogenase (LDH) were measured at post-transplant days 1 and 3. The primary outcome was the occurrence of delayed graft function (DGF). Descriptive and receiver operating characteristic analyses were performed. Results Forty-one patients were included in the analysis: 15 (36.59%) DCD KTs (9 of which suffered from DGF) and 26 (63.41%) living donor KTs. For the primary endpoint, neutrophil gelatinase-associated lipocalin, N-acetyl-beta-D-glucosaminidase, urinary tubular injury biomarker-to-creatinine ratio, and LDH areas under the curve were 1 and 0.96 (95% confidence interval: 0.84-1.0), 1 and 0.92 (95% confidence interval: 0.73-1.0), respectively. Among the transplant characteristics, only the 30-minute resistive index on the perfusion machine was significantly higher in DCD KTs with DGF vs those without DGF (0.26 mm Hg/mL/min [0.20; 0.32] vs 0.14 mm Hg/mL/min [0.12; 0.16], P = .05). Median 3-month creatinine clearance among DGF DCD KTs was 49 mL/min/1.73 m2 [IQR: 42; 65] and 65 mL/min/1.73 m2 [IQR: 62; 66] among DCD KTs without DGF (P = .22). Conclusion In the DCD KT population, clinical and biological markers were identified that provided predictive tools for DGF. Thus, systematic measurement of these biomarkers, particularly LDH, could improve the management of kidney graft recipients’ immunosuppressive therapy.

Idiopathic nephrotic syndrome (INS) represents 15%–30% of adulthood glomerulopathies. Corticosteroids have been the main treatment for decades and are effective in 70% of minimal-change disease patients and ~30% of focal segmental glomerulosclerosis patients. Multidrug-resistant (steroids, calcineurin-inhibitors, cyclophosphamide, mycophenolate-mofetil, rituximab) idiopathic nephrotic syndrome is a major therapeutic challenge in nephrology. Apheresis (double-filtration plasmapheresis or semi specific immunoadsorption) could act by eliminating the circulating factor (apolipoproteinA1b, solubleCD40L, suPAR) increasing glomerular permeability seen in INS. The aim of the study was to report the outcome of three patients with multidrug-resistant INS treated successfully with apheresis.

Objectives Chronic antibody-mediated rejection is the main cause of late kidney graft loss. The presence of donor-specific antibodies in the serum is the main criterion for this diagnosis. Single antigen Luminex assays can identify donor-specific antibodies, and semiquantitative estimates of antibodies can be assessed using mean fluorescence intensity. Recent data have shown that patients whose donor-specific antibodies fix C3d have worse clinical outcomes, implying that C3d-specific Luminex assays may provide useful prognostic data. Materials and methods We compared C3d donor-specific antibodies with standard immunoglobulin G donor-specific antibody mean fluorescence intensities in a cohort of patients with de novo class II donor-specific antibodies and analyzed subsequent graft survival. The included kidney graft recipients received transplants between 2005 and 2015 and had developed de novo class II donor-specific antibodies. Serum was tested using the standard single antigen Luminex technique and the C3d-fixing antibody-detection system (Immucor, Herentals, Belgium). Results In our patient cohort, 41/924 patients (4.4%) developed class II donor-specific antibodies, and 65 serum samples were analyzed (at baseline and follow-up). Among these samples, 43 (66%) were negative for C3d donor-specific antibodies. A mean fluorescence intensity threshold of 9000 in the single antigen Luminex assay discerned all negative (from positive) C3d donor-specific antibodies, even when all single-bead results were taken into account. Sixteen patients (39%) had poor outcomes (ie, either creatinine levels had doubled or they had lost their graft) over the median follow-up of 5 years. C3d results were significantly associated with graft survival (P = .04). We found a strong correlation between C3d-fixing antibody positivity and mean fluorescence intensity strength in the setting of de novo class II donor-specific antibodies. Conclusions These results further reinforce the paradigm that the higher the mean fluorescence intensity, the more complement activation occurs. Routine C3d testing is thus unnecessary in this setting.

BACKGROUND The DIAMOND study of de novo liver transplant patients showed that prolonged-release tacrolimus exposure in the acute post-transplant period maintained renal function over 24 weeks of treatment. To assess these findings further, we performed a post-hoc analysis in patients according to baseline kidney function, Model for End-stage Liver Disease [MELD] scores, and donor age. MATERIAL AND METHODS Patients received prolonged-release tacrolimus (initial-dose, Arm 1: 0.2 mg/kg/day, Arm 2: 0.15-0.175 mg/kg/day, Arm 3: 0.2 mg/kg/day delayed until Day 5), mycophenolate mofetil and 1 steroid bolus. Arms 2 and 3 also received basiliximab. The recommended tacrolimus target trough levels to Day 42 post-transplantation were 5-15 ng/mL in all arms. In this post-hoc analysis, change in renal outcome, based on estimated glomerular filtration rate (eGFR), Modified Diet in Renal Disease-4 (MDRD4), values from baseline to Week 24 -post-transplantation, were assessed according to baseline patient factors: eGFR (≥60 and ˂60 mL/min/1.73 m²), MELD score (˂25 and ≥25) and donor age (˂50 and ≥50 years). RESULTS Baseline characteristics were comparable (Arms 1-3: n=283, n=287, n=274, respectively). Patients with baseline renal function, eGFR ≥60 mL/min/1.73 m², experienced a decrease in eGFR in all tacrolimus treatment arms. In patients with lower baseline renal function (eGFR ˂60 mL/min/1.73 m²), an advantage for renal function was observed with both the early lower-dose and delayed higher-dose tacrolimus regimens compared with the early introduction of higher-dose tacrolimus. At Week 24, renal function was higher in the early-lower tacrolimus arm with older donors, and the delayed higher-dose tacrolimus arm with younger donors, both compared with early higher-dose tacrolimus. CONCLUSIONS Pre-transplantation factors, such as renal function and donor age, could guide the choice of prolonged-release tacrolimus regimen following liver transplantation.

Resume Connue depuis un peu moins d’un demi-siecle, la borreliose, ou maladie de Lyme, est une zoonose transmise par la tique. Elle est la maladie vectorielle la plus rependue en Europe et aux Etats-Unis. Le Borrelia burgdorferi sensu lato, la bacterie en cause, est dote d’un « systeme de ruse » qui lui permet de dejouer la defense immunitaire et d’implanter l’infection sur le mode chronique. Il engendre des lesions tissulaires multisystemiques mediees par la reponse inflammatoire de l’hote. L’atteinte renale est rarement rapportee et elle est mieux connue chez le chien sous l’appellation de nephrite de Lyme. Le premier cas d’atteinte renale chez l’homme est decrit en 1999 et, depuis, huit autres cas ont ete rapportes. L’atteinte est preferentiellement glomerulaire et les formes histologiques varient entre les nephropathies a depots de complexes immuns et la podocytopathie. Les mecanismes physiopathologiques semblent etre triples : depots de complexes immuns, hyperexpression podocytaire de la proteine membranaire B7-1, et infiltration renale de cellules inflammatoires. En se basant sur les connaissances accumulees sur la maladie en un peu plus de 40 ans, l’objectif de cette revue est d’etablir les hypotheses physiopathologiques de l’atteinte renale afin de mieux definir les lesions histologiques.

Tacrolimus-based immunosuppression remains the immunosuppressive drug of choice in kidney transplantation.Its safety profile is closely linked to its pharmacokinetic properties. A narrow therapeutic range allows to limit under- and over-immunosuppression consequences. Minimization of tacrolimus exposure, using appropriate companion drugs, leads to the best renal outcomes in the long term. Also, reducing tacrolimus exposure variability helps in reducing tacrolimus toxicity. The novel concept of tacrolimus concentration-to-dose ratio (C/D ratio) associates with renal outcomes as well and provides some new possible improvements on tacrolimus safety, possibly by identifying kidney transplant recipient subpopulations at higher risk of tacrolimus toxicity. Similarly, the incidence of new-onset diabetes after transplantation (NODAT), a major side-effect of tacrolimus, can also be reduced by optimizing tacrolimus exposure. In this review, the authors summarize the safety profile of tacrolimus when optimizing mean tacrolimus exposure, tacrolimus exposure variability and tacrolimus C/D ratio. The impact of these adjustments on nephrotoxicity and NODAT is reviewed. Using such prescription optimization, tacrolimus' safety profile is positive.Tacrolimus-based immunosuppression remains a valid option for kidney transplant recipients, and might even improve by individualizing prescriptions, the next frontier in transplant immunosuppression.

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 &lt, 0.001). Among the PKB+ patients, 87 recipients (26%) had IF/TA &gt, 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.

Significance Statement This randomized trial demonstrates the safety and efficacy of conversion from calcineurin inhibitor (CNI)? to belatacept-based maintenance immunosuppression in renal transplant recipients 6?60 months post-transplant. Patients converted to belatacept showed sustained improvement in renal function associated with an acceptable safety profile consistent with prior experience and a smaller treatment difference in acute rejection postconversion compared with that observed in earlier studies in de novo renal allograft recipients. These results favor the use of belatacept as an alternative to continued long-term CNI-based maintenance immunosuppression, which is particularly relevant for CNI-intolerant patients, including those who experience nephrotoxicity. These data help inform clinical practice guidelines regarding the conversion of such patients to an alternative immunosuppressive drug regimen.Background Calcineurin inhibitors (CNIs) are standard of care after kidney transplantation, but they are associated with nephrotoxicity and reduced long-term graft survival. Belatacept, a selective T cell costimulation blocker, is approved for the prophylaxis of kidney transplant rejection. This phase 3 trial evaluated the efficacy and safety of conversion from CNI-based to belatacept-based maintenance immunosuppression in kidney transplant recipients.Methods Stable adult kidney transplant recipients 6?60 months post-transplantation under CNI-based immunosuppression were randomized (1:1) to switch to belatacept or continue treatment with their established CNI. The primary end point was the percentage of patients surviving with a functioning graft at 24 months.Results Overall, 446 renal transplant recipients were randomized to belatacept conversion (n=223) or CNI continuation (n=223). The 24-month rates of survival with graft function were 98% and 97% in the belatacept and CNI groups, respectively (adjusted difference, 0.8; 95.1% CI, ?2.1 to 3.7). In the belatacept conversion versus CNI continuation groups, 8% versus 4% of patients experienced biopsy-proven acute rejection (BPAR), respectively, and 1% versus 7% developed de novo donor-specific antibodies (dnDSAs), respectively. The 24-month eGFR was higher with belatacept (55.5 versus 48.5 ml/min per 1.73 m(2) with CNI). Both groups had similar rates of serious adverse events, infections, and discontinuations, with no unexpected adverse events. One patient in the belatacept group had post-transplant lymphoproliferative disorder.Conclusions Switching stable renal transplant recipients from CNI-based to belatacept-based immunosuppression was associated with a similar rate of death or graft loss, improved renal function, and a numerically higher BPAR rate but a lower incidence of dnDSA. Clinical Trial registry name and registration number: A Study in Maintenance Kidney Transplant Recipients Following Conversion to Nulojix? (Belatacept)-Based, NCT01820572

Background and Aims Studies of healthy individuals or candidates for living kidney donation, in various geographical areas and ethnic groups, describe a decline of glomerular filtration rate (GFR) with age. Most data on GFR are obtained from subjects in the general population or from candidates for kidney donation who are younger than 65 years. It is currently unknown whether the definition of normal GFR in subjects older than 65 years is similar to the definition in those younger than 65 years. Because the age of candidates for living kidney donation is increasing worldwide, lack of GFR references for older donors complicates the selection process. Moreover, older individuals are most likely to have a mildly decreased GFR that may be misinterpreted as chronic kidney disease. In this study, we calculated percentiles of measured GFR (mGFR) from a large cohort of effective kidney donors (EKD) younger than 65 years, and extrapolated them to subjects older than 65 years. Additionnaly, we collected mGFR data from different centers within Europe from EKD and/or healthy people (HP) from the general population older than 65 years. We tested if the distribution of mGFR of these older subjects fitted with the extrapolated percentiles. Method In this retrospective, observational, multi-center study, percentiles of mGFR in EKD were calculated from a development cohort of French and Belgian EKD younger than 65 years (n=1983). From the French kidney donor study, 147 EKD older than 65 years were considered as the internal validation cohort. In an external validation cohort, data on mGFR of subjects older than 65 years, either EKD or HP from the general population (from Germany, Sweden (2), Norway, Netherlands and France, n=2459) were included. Data were fully anonymized and this retrospective study was approved by the respective ethics committees. Percentiles were derived for the development database, using quantiles modeled as cubic splines with two linear parts joining at one age-knot of 40 years. The median quantile had a constant first part (slope of zero) and a second part with a negative slope of -0.88235 mL/min/1.73m² per year. To maintain consistency, all quantiles were adjusted to show the same shape as the medium quantile. Above 65 years, the percentile values were extrapolated using the same mathematical model. We then calculated the percentage of results from the internal and external validation cohorts that were within the 5th extrapolated percentile (P5) and 95th percentile (P95). A sensitivity analysis including the EKD only was performed. Results Individuals in the development cohort were younger than in the internal or external validation cohort (47.3±10.5 years vs. 68.8±2.9 years and 71.4±6.4 years; respectively, both p Conclusion We demonstrate that extrapolated percentiles of mGFR (calculated in individuals younger than 65) fits well with the distribution of mGFR in individuals older than 65. Extrapolation of percentiles to individuals older than 65 is useful to define age-adapted GFR thresholds for older individuals.

Background Long-term studies have demonstrated a slight increased risk for end-stage renal disease (ESRD) for living kidney donors (LKD). In France, living kidney donation doubled within the past 10 years. We investigated the change in characteristics of LKD between 2007 and 2017 and the adequacy of follow-up. Methods Data were obtained from the national registry for LKD. We compared characteristics of LKD between two study periods: 2007–11 and 2012–17, and stratified donors by age and relation to recipient. We aggregated four characteristics associated with higher ESRD risk [young age, first-degree relation to recipient, obesity, low glomerular filtration rate (GFR) for age] in a single risk indicator ranging from 0 to 4. Results We included 3483 donors. The proportion of unrelated donors >56 years of age increased significantly. The proportion of related donors Conclusions An increase in living kidney donation in France does not seem to be associated with the selection of donors at higher risk of ESRD and the proportion of donors with adequate annual follow-up significantly increased.

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., Graphical abstract

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.

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 &lt, 0.01). Safety was good: severe adverse events occurred in 17 sessions (1.9%), more frequently with DFPP (6.5%) p &lt, 0.01. Hypotension occurred in 154 sessions (17.5%), more frequently with DFPP (p &lt, 0.01). Apheresis is well tolerated (IA and PE &gt, DFPP) and effective at removing HLA antibodies and allows HLAi KT for sensitized patients.

Background Resistance to the action of rituximab (RTX) has been documented in several diseases. More recently, obinutuzumab (OBZ) has shown promise where RTX has failed in oncology and lupus nephritis. Unlike RTX, OBZ is a weak activator of complement, which may avoid the false-positive complement-dependent cytotoxicity (CDC) crossmatch tests after RTX infusions. Methods The aim of this study was to explore the effect of OBZ on B-cell depletion in kidney-transplant candidates and its impact on crossmatch test results. We included 12 patients: who were either highly sensitized kidney-transplant candidates or kidney-transplant recipients presenting with antibody-mediated rejection. Six received OBZ and 6 received RTX. CD-19 counts, flow cytometry and CDC crossmatch tests were run immediately before and at 2 weeks after drug infusion. Results OBZ reduced CD-19 counts: median reduction was 98%. B-cell CDC crossmatch test results became positive following RTX infusion but were not affected by OBZ infusion. Conclusions OBZ effectively depleted B-cell counts in sensitized kidney-transplant candidates and, unlike RTX, had no effect on CDC crossmatch results.

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.

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&ndash, 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 +/&minus, 13 months. OPIs developed in 42(9.3%) patients after 14 +/&minus, 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 &lt, 0.001, and 11.6% vs. 2.4%, p &lt, 0.001, respectively). Cumulative incidence of OPIs was 6.5 OPIs/100 person&ndash, years. Incidence of CMV disease was 2.8/100 person&ndash, years, of pneumocystis pneumonia 1.6/100 person&ndash, years, and of aspergillosis 0.2/100 person&ndash, years. Multivariate analyses showed that estimated glomerular filtration (eGFR) &lt, 25 mL/min/1.73 m2 at conversion was independently associated with OPIs (HR = 4.7 (2.2 &minus, 10.3), p &lt, 0.001). The incidence of EBV DNAemia was 17.3 events /100 person&ndash, years. At 1-year post-conversion, mean eGFR had significantly increased from 32.0 +/&minus, 18 mL/min/1.73 m2 to 42.2 +/&minus, 18 mL/min/1.73 m2 (p &lt, 0.0001). Conversion to belatacept is an effective strategy with a low infectious risk.

Summary Due to the Covid‐19 pandemic caused by SARS‐CoV‐2, transplant programs worldwide have been severely impacted with dwindling numbers of transplantations performed and a complete halt in several areas. In this review we examine whether SARS‐CoV‐2 infection presents differently in transplant recipients, whom and how we should test, how susceptible the transplant population is to overt infection and describe the range of outcomes. From retrieved published reports on SARS‐CoV‐2infections in 389solid organ transplant recipients reported in the literature, the overall mortality rate was 16.7% (n = 65); however for those with mild or moderate Covid‐19 disease this was 2.9% and 2.3% respectively; conversely, for those with severe infection the mortality rate was 52.2%.We then address questions regarding halting transplantation programs during this pandemic, whether all human tissues being considered for transplantation are capable of transmitting the infection, and if we should alter immunosuppressive medications during the pandemic.

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 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.

Background The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved. Methods In a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation. Results 7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels Conclusions None of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.

Background and Aims Great progression in treating hepatitis C infection has been made with the new Interferon-free regimens. Reports about developing hepatocellular carcinoma after DAAs have been spotlighted. Kidney transplantation and hemodialysis are considered risk factors for developing malignancies. Here we are evaluating the prevalence of HCC after DAAs treatment in high risk population. Method This cross-sectional study was held in Urology and Nephrology Center, Mansoura University, Egypt including. Total number of 165 patients received DAAs included in this study in 2 phases. The first phase included 50 patients (12 hemodialysis and 38 kidney transplant recipients). All patients completed DAAs course as treatment for hepatitis C infection (HCV) 24 months ago. Alfa feto protein and liver ultrasound (Use of both modalities combined yielded sensitivity (99.2%) and specificity (68.3%)) was used to screening of HCC for all patients. Triphasic CT liver with 86% to 94% sensitivity was done for all hemodialysis patients and KTRs with suspicious lesions or high alfa-feto protein. Results Our patients mean age was 52.32±3.2 years with male predominance. Mean Hemodialysis duration was 48.21±12.3 months and mean kidney transplantation duration was 36.21±6.7 months. Baseline laboratory investigations: ALT: 39.17±16.3 iu/l, Albumin: 3.6±1.32 g/dl, Bilirubin: 0.54±0.21, Hemoglobin: 10.57±1.9 g/dl, AFP: 5.3±2.4 ng/ml. Baseline liver US: normal (49%), enlarged (42%) and cirrhotic (9%) (No focal lesions). Fibro scan: F0 (26%), F1 (31%), F2 (32%) and F3 (11%). None of them experienced hepatic encephalopathy attacks or bleeding varices. All hemodialysis patients received Ombitasvir/Paritaprevir/Ritonavir (OMV/PTV/RTV) regimen (3 months). Only 2 KTRs received OMV/PTV/RTV regimen (3 months), the remaining 36 KTRs received Sofosbuvir/Daclatasvir regimen (6 months). Only 1 case reported relapse within 3 month after completing treatment. The rest achieved 12-week and 24-week SVR successfully. After 2 years from completing treatment, there was significant improvement in ALT levels. Four KTRs passed to graft failure due to accelerated immunologic response (rejection episodes) and 7 KTRs showed rise of serum creatinine (biopsy-proven rejection). Mean AFP rose up to 7.6±2.4 ng/ml with no statistical difference. Three hemodialysis patients and 4 KTRs showed rise in alfa-feto protein above normal values (10ng/dl). Four out of them exceeded 500ng/ml (1 HD and 3 KTRs). Abdominal US revealed: no change (39 patients), enlargement (6 patients) and cirrhosis (5 patients). Suspicious mass was found in 11 patients. Triphasic CT then was done for all hemodialysis patients and 9 KTRs. Regarding hemodialysis, 1 patient was diagnosed as HCC based on increased enhancement by Triphasic CT and alfa-fetoprotein was >500 ng/ml. Regarding KTRs, HCC was diagnosed in 2 patients and liver metastasis secondary to lymphoma was diagnosed in 1 case. The other patients with suspicious lesions (5 patients) showed uniform enhancement by Triphasic CT suggesting benign lesions. So, we have 3 (6%) out of 50 patients has been diagnosed as HCC after DAAs. By retrieval of their data, HCV duration was over 10 years and the liver was cirrhotic or enlarged with cirrhotic changes by ultrasound. Baseline ALT was slightly high without significant improvement after treatment. Also, baseline alfa-feto protein was high. The 3 patients were F2 or F3. Conclusion Hepatocellular carcinoma incidence after Direct-acting anti-virals is related mostly to the poor condition of the patients at baseline not to the drug itself and HCC in such cases could be considered as a part of disease progression not a drug complication.

Background and Aims With the advance of new direct acting antiviral, treatment of HCV became safer and easier. Renal impairment makes treatment of HCV more difficult due to poor drug tolerability. Anemia is a common side effect occurring in renal patients. Effect of anemia on the efficacy and safety of these drugs in those particular populations is a point of interest. Method This is a single center cohort study was held in Urology and Nephrology Center, Mansoura, Egypt, including 235 renal patients who were divided into 2 groups according to presence/absence of anemia; hemoglobin below 10.5 g/dL is considered cut-off value: 70 chronic kidney disease patients (CKD) (42 anemic and 28 non-anemic), 40 hemodialysis patients (HD) (24 anemic and 16 non-anemic) and 125 kidney-transplant recipients (KTRs) (40 anemic and 85 non-anemic). Hemodialysis patients received ritonavir-boosted paritaprevir and ombitasvir±ribavirin (OMV/PTV/RTV), KTRs received sofosbuvir and daclatasvir. CKD with eGFR >30 ml/min/1.73m2 received sofosbuvir and daclatasvir. CKD with eGFR Results: Demographics: Mean age was 49.17y for CKD, 43.2y for HD and 45.2y for KTRs. Most of them were males with body mass index around 23.8. Out of 235, 22 patients had been previously treated with interferon-IFN- (14 patients showed relapse after primary response on IFN and 8 patients could not tolerate IFN due to severe anemia, leucopenia and recurrent infection) and 7 patients had been co-infected with hepatitis B virus (all patients were cleared from the virus prior to HCV treatment). Efficacy: Rapid virologic response was achieved in all groups. 12-week sustained viral response (SVR-12) among CKD patients was 92.86% in anemic group and 96.42% in no-anemic group (p=91%). SVR-24 was lower in both groups. There were 16 relapse cases among CKD patients (11 in anemic group and 5 in non-anemic group; p value=0.69). Relative Risk for relapse incidence among anemic CKD patients was 1.4 with 95% CI 3.58 to 8.58 (p value: 0.42). Among HD patients, there was only 1 relapse case and it was in anemic group. All KTRs achieved SVR-12 and SVR-24. Safety: Deterioration of kidney function within 1 month from starting DAAs was the major side effect in both groups among CKD patients but it was more profound in anemic group (59.5%) (p value: 0.024). Deterioration of creatinine clearance was more obvious in anemic group (26.7±11.8mL/min, 21.28±12.97mL/min; p value: 0.014). More cases needed hemodialysis either temporary (3 cases) or permanently (13 cases) in anemic group (p value: 0.03 for temporary hemodialysis and 0.005 for permanent hemodialysis). Relative Risk for A/CKD incidence with anemia among CKD patients was 1.85 with 95% CI from 22.94 to 1.98 (p value: 0.04). Anemia was associated with rise of serum creatinine among kidney transplant recipient also. Graft impairment among anemia group was 30% (12 out of 40 patients) in comparison to 3.5% in no-anemia group (3 out of 85 patients); p value: 0.0002. Relative Risk for graft impairment with anemia among KTRs was 8.5 with 95% CI 6.95 to 2.64. Subsequently, drug interruption was more frequent among anemia group in both CKD and KTRS as treatment was suspended during AKI period. Regarding hemodialysis patients, the only difference was that worsening of anemia was more frequent among no-anemia group (p value: 0.0002). Ribavirin resulted in this this difference as no-anemia group received ribavirin while the other group did not receive it. Conclusion Direct-acting anti viral drugs are considered advance in treatment of hepatitis C infection and it is well tolerated by kidney disease patients. However, this particular population needs special care. Correction of anemia before starting DAAs may improve the outcome. Hemoglobin levels below 10.5 g/dL prior to DAAs are associated with rise of serum creatinine among KTRs and CKD patients.

Chronic hepatitis-C infection is a great health burden in Egypt. The effect of anemia on the efficacy and safety of direct-acting anti-viral (DAA) therapies for those with chronic-kidney disease (CKD) has not been evaluated. This single-center retrospective study included 235 renal patients: i.e., 70-CKD patients not on hemodialysis (42 with anemia, 28 without); 40 hemodialysis patients (16 anemic; 24 non-anemic), and 125 kidney-transplant (KTx) recipients (40 anemic; 85 non-anemic). Anemia was defined by a hemoglobin level 30 mL/min/1.73 m2 received sofosbuvir/daclatasvir. Those with eGFR

Recommendations on the glomerular filtration rate (GFR) threshold compatible with living kidney donation are not agreed upon. The recent KDIGO guidelines suggested a reset of the conventional cutoff value of 80 to 90 mL/min/1.73 m2. While GFR physiologically declines with age, it is unclear whether and how age should be taken into account for selecting acceptable pre-donation GFR. In this multicenter retrospective study encompassing 2007 kidney donors in France, we evaluated the impact of age using two threshold measured GFR (mGFR)s (80 and 90 mL/min/1.73 m2). Three groups of donors were defined according to baseline mGFR: below 80, 80-89.9 and 90 mL/min/1.73 m2 or more. Thirty-two percent of donors were selected despite an mGFR below 90 mL/min/1.73 m2. Donors with the lowest mGFR were significantly older (60 ± 9 vs. 47 ± 11 years) and this applied to both male and female donors. The lifetime-standardized renal reserve, defined as the pre-donation mGFR value divided by the expected number of remaining years of life, was similar irrespective of baseline mGFR groups. Similar results were obtained when eGFR was used instead of mGFR. Finally, in a subgroup of 132 donors with repeated mGFR five years after donation, the magnitude of mGFR decrease was similar in all groups (-34.3%, -33.9%, and -34.9% respectively). Thus, the decision to accept individuals with mGFR lower than 90 mL/min/1.73 m2 for kidney donation is highly dependent on the age of the candidate. Hence, threshold values lower than 90 mL/min/1.73 m2 are reasonable for older donors. Age-calibrated mGFR may improve efficiency of the selection process.

Background Anti-glomerular basement-membrane (anti-GBM) disease (or Goodpasture disease) is characterized by severe kidney and lung involvement. Prognoses have improved with treatments that combine plasma exchange and immunosuppressive drugs. However, patients with severe renal involvement can have poor renal outcomes and cyclophosphamide can cause significant complications. Anti-GBM antibodies have a direct pathogenic effect on the disease: thus, therapeutics that can decrease their production, such as rituximab, could be a good alternative. Methods The medical files of five patients that had received rituximab as a first-line therapy (instead of cyclophosphamide), plus plasma exchange and steroids, were reviewed. All patients had severe disease manifestations. Results Four patients required dialysis at diagnosis and remained dialysis-dependent over the mean follow-up of 15 months. Three patients had pulmonary involvement, but recovered even though mechanical ventilation was required. Anti-GBM antibodies became rapidly undetectable in all patients. One infectious and two hematological complications were observed. Conclusions We report the outcomes of five patients with Goodpasture disease and treated with rituximab as a first-line treatment. This strategy was effective at treating pulmonary manifestations and was associated with a good biological response with no major serious adverse events. However, renal outcomes were not significantly improved.

Cornerstone immunosuppressive therapy currently relies on immediate-release tacrolimus, a calcineurin inhibitor (CNI) that is potentially nephrotoxic and is more diabetogenic than cyclosporine A. Two new formulations of tacrolimus have been launched: an extended-release formulation (Advagraf®/Astagraf XL®, Astellas company) and a long-lasting formulation (Envarsus®, Veloxis company). Area covered: Herein, we assess the efficacy of an extended-release formulation of tacrolimus (Advagraf®/Astagraf XL®) used in conjunction with or without an induction therapy (i.e., basiliximab) in de novo kidney-transplant recipients. To achieve this, we searched for suitable articles through PubMed. Expert commentary: Phases-III and -IV studies comparing Advagraf®/Astagraf XL® to Prograf® in association with mycophenolate mofetil (more than 2,500 patients) have demonstrated overall similar results with regards to patient/graft survival, biopsy-proven acute-rejection rate, and renal function (p 0.05). A randomized controlled study in maintenance kidney transplant patients has shown (using electronic monitoring) that, as compared to Prograf®, Advagraf® significantly improved adherence to medication. Other studies report that Advagraf®-treated patients receiving a mTOR-inhibitor agent (sirolimus or everolimus) instead of MMF: this was associated with good allograft outcome, and might also prevent late-onset cytomegalovirus infection. Advagraf®-based immunosuppression given to de novo kidney-transplant recipients, with or without an induction therapy, provided excellent results compared to Prograf®; it also increased patients' adherence to treatment.

We herein describe the first case of thrombotic microangiopathy (TMA) which was related to Shiga toxin producing-Escherichia Coli Hemolytic and Uremic Syndrome (STEC-HUS) after lung transplantation. His maintenance immunosuppression relied on tacrolimus plus mycophenolic acid. TMA was treated with plasma exchanges (PE) (fresh frozen plasma substitution). After five days of PE, platelets count and lactate dehydrogenase level normalized, whereas hemoglobin continued to gradually decrease and no improvement in kidney function was observed. After seven PE sessions, all TMA biological signs resolved. However, kidney function did not improve, and the patient still required chronic dialysis.