Management of pediatric patients with a failing kidney transplant:A survey of UK‐based renal units

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European Guideline for the Management of Kidney Transplant Patients With HLA Antibodies:By the European Society for Organ Transplantation Working Group

This guideline, from a European Society of Organ Transplantation (ESOT) working group, concerns the management of kidney transplant patients with HLA antibodies. Sensitization should be defined using a virtual parameter such as calculated Reaction Frequency (cRF), which assesses HLA antibodies derived from the actual organ donor population. Highly sensitized patients should be prioritized in kidney allocation schemes and linking allocation schemes may increase opportunities. The use of the ENGAGE 5 ((Bestard et al., Transpl Int, 2021, 34: 1005–1018) system and online calculators for assessing risk is recommended. The Eurotransplant Acceptable Mismatch program should be extended. If strategies for finding a compatible kidney are very unlikely to yield a transplant, desensitization may be considered and should be performed with plasma exchange or immunoadsorption, supplemented with IViG and/or anti-CD20 antibody. Newer therapies, such as imlifidase, may offer alternatives. Few studies compare HLA incompatible transplantation with remaining on the waiting list, and comparisons of morbidity or quality of life do not exist. Kidney paired exchange programs (KEP) should be more widely used and should include unspecified and deceased donors, as well as compatible living donor pairs. The use of a KEP is preferred to desensitization, but highly sensitized patients should not be left on a KEP list indefinitely if the option of a direct incompatible transplant exists.</p

Theory and practice: bulk synthesis of C3B and its H2- and Li-storage capacity.

Previous theoretical studies of C3B have suggested that boron-doped graphite is a promising H2- and Li-storage material, with large maximum capacities. These characteristics could lead to exciting applications as a lightweight H2-storage material for automotive engines and as an anode in a new generation of batteries. However, for these applications to be realized a synthetic route to bulk C3B must be developed. Here we show the thermolysis of a single-source precursor (1,3-(BBr2)2C6H4) to produce graphitic C3B, thus allowing the characteristics of this elusive material to be tested for the first time. C3B was found to be compositionally uniform but turbostratically disordered. Contrary to theoretical expectations, the H2- and Li-storage capacities are lower than anticipated, results that can partially be explained by the disordered nature of the material. This work suggests that to model the properties of graphitic materials more realistically, the possibility of disorder must be considered.We thank the ERC (Advance Investigator awards for D.S.W., C.P.G.), the EPSRC (T.C.K., P.D.M., H.G., J.C.), and the Spanish Ministerio de Economia y Competitividad (under grants ENE2011-24-412 and IPT-2011-1553-420000). We thank John Bulmer for Raman spectroscopy and Keith Parmenter for glass blowing. We thank the Schlumberger Gould Research Centre for XPS analysis.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/anie.20141220

Rituximab in adult minimal change disease and focal segmental glomerulosclerosis - What is known and what is still unknown?

Primary forms of minimal change disease and focal segmental glomerulosclerosis are rare podocytopathies and clinically characterized by nephrotic syndrome. Glucocorticoids are the cornerstone of the initial immunosuppressive treatment in these two entities. Especially among adults with minimal change disease or focal segmental glomerulosclerosis, relapses, steroid dependence or resistance are common and necessitate re-initiation of steroids and other immunosuppressants. Effective steroid-sparing therapies and introduction of less toxic immunosuppressive agents are urgently needed to reduce undesirable side effects, in particular for patients whose disease course is complex. Rituximab, a B cell depleting monoclonal antibody, is increasingly used off-label in these circumstances, despite a low level of evidence for adult patients. Hence, critical questions concerning drug-safety, long-term efficacy and the optimal regimen for rituximab-treatment remain unanswered. Evidence in the form of large, multicenter studies and randomized controlled trials are urgently needed to overcome these limitations

Long-Term Efficacy and Safety of the Long-Acting Complement C5 Inhibitor Ravulizumab for the Treatment of Atypical Hemolytic Uremic Syndrome in Adults

Introduction: Atypical hemolytic uremic syndrome (aHUS) is a rare, complex, multisystem disease of dysregulated complement activity, characterized by progressive thrombotic microangiopathy (TMA), acute kidney injury, and multiorgan dysfunction, which often progresses to chronic kidney disease. Results from the prospective clinical trial of ravulizumab (NCT02949128) reveal rapid resolution of TMA in patients with aHUS, with sustained efficacy and safety in a 26-week initial evaluation period. Methods: The aim of this analysis was to characterize the long-term efficacy and the safety profile of ravulizumab in adults with aHUS who had completed the initial evaluation period of the trial. Complete TMA response, hematologic and kidney functions, and safety were evaluated for all patients available for follow-up in the extension period (median follow-up: 76.7 weeks; range: 0.6–118.3). This trial included a total of 58 patients, 49 of whom entered the extension period. Results: A total of 4 additional patients achieved complete TMA response during the follow-up period. Normalization of platelet count, serum lactate dehydrogenase (LDH), and hemoglobin observed in the 26-week initial evaluation period was sustained until the last available follow-up, as were the improvements in the estimated glomerular filtration rate (eGFR) and patient quality of life. All efficacy endpoints were correlated with the sustained inhibition of complement C5. Most adverse events (AEs) occurred early during the initial evaluation period and decreased substantially during the extension period. No patient developed a meningococcal infection or died during the extension period. Conclusion: This analysis reveals that ravulizumab administered every 8 weeks is efficacious with an acceptable safety profile for the long-term treatment of adults with aHUS and provides additional clinical benefit beyond 6 months of treatment