Nephrologie & Therapeutique最新文献

Background

Desensitization allows kidney transplantation for HLA highly sensitized subjects. Due to the central role of IL-6 in immunological response, tocilizumab (monoclonal antibody directed against IL-6 receptor) could probably improve desensitization efficacy.

Methods

Pubmed systematic review by using MeSH terms: tocilizumab, clazakizumab, interleukin-6 blockade, kidney transplantation, kidney graft and desensitization.

Studies

IL-6 plays a role in humoral response (plasmocyte differentiation induced by lymphocyte T, IL-21 secretion) as well as in cellular response (differentiation of LT Th17 rather than T reg). In desensitization field, tocilizumab was first studied as second-line treatment after failing of standard-of-care (apheresis, rituximab ± IgIV). Recent study showed that tocilizumab as a monotherapy attenuated anti-HLA antibodies rates but was not sufficient to allow transplantation. However, lymphocyte immunophenotyping showed that tocilizumab hindered B cells maturation. Thereby, tocilizumab could improve long-term efficacy of desensitization, by limiting the anti-HLA rebound and so avoiding antibody-mediated rejection. This hypothesis is supported by a recent study which used clazakizumab (monoclonal antibody directed against IL-6) in association with standard-of-care. In that study, clazakizumab was continued after kidney transplantation. Results were encouraging because 9/10 patients were transplanted and there was no donor-specific antibody at 6 months post-transplantation.

Conclusion

IL-6 pathway blockade as a monotherapy fails to desensitize HLA highly sensitized kidney transplant candidates. In association with standard-of-care, it does not seem to significatively improve kidney allograft access (short-term efficacy) vs. standard-of-care only. However, it could improve long-term prognosis of HLA incompatible transplantation by orienting the response towards a tolerogenic profile, by hindering B-cell maturation and, thereby, avoiding DSA rebounds after transplantation. This hypothesis needs to be proven by further studies.

Introduction

Transplantation from controlled donation after circulatory determination of death (cDCD) is a new practice in France. An additional specific consent is required for registration on the cDCD waiting list. The aim of this study is to evaluate the impact of cDCD acceptance on the waiting time for the registered patients on the transplant list.

Methods

Patients registered on the kidney transplant waiting list for a Death Brain Donor (DBD) kidney transplant between 2018 and 2019 in our center were included. Patients who were candidates for a second kidney transplant or who had already received an organ transplant were not included. The cDCD waiting list registration was authorized by a signed consent of the patient on the day of DBD registration. The primary endpoint was time to renal transplantation.

Results

Of the 315 patients eligible for a cDCD graft at transplant list registration, 152 were registered on the cDCD waiting list. Time to transplantation for these patients was multiplied by 1.42 (95%CI 1.07–1.87) compared with patients not registered for a cDCD graft. The time to transplantation was 2.59 months (95%CI 0.49–4.69) shorter for a 2-year follow-up for cDCD-listed patients. This represents one additional transplant at 6 months for every seven registered patients.

Conclusion

cDCD waiting list registration reduced the time to kidney transplantation in France.

We describe here the case of a 54-year-old bipolar woman, followed in psychiatry and treated with lithium and a selective serotonin reuptake inhibitor (escitalopram) and lamotrigine, presenting a lithium poisoning with an altered state of consciousness caused by a supposed mismanagement of her treatment. Lithium poisoning was suggested based on neurological clinical features, but the blood test brought out a lithium concentration within the therapeutic values at 1,2 mmol/L (N: 0,6–1,2 mmol/L). The classic biological complications related to lithium poisoning (hypercalcemia, diabetes insipidus) confirmed the diagnosis. The patient has been transferred to our nephrology department where she got two hemodialysis sessions conducting to clinical and biological improvement, confirming the diagnosis of lithium poisoning despite the normal blood levels. Later, she was transferred to the psychiatry department for follow-up and for treatment adjustment.

L’anémie est une complication fréquente de la maladie rénale chronique (MRC). Le défaut de production d’érythropoïétine (EPO) par les reins et la carence martiale en sont les principales causes. De fait, la supplémentation en fer et l’administration d’EPO recombinante représentent les bases de sa prise en charge. De nouvelles formulations de fer administrables par voie orale, intraveineuse ou directement via le dialysat ont été développées récemment pour en améliorer l’efficacité et la tolérance. Le citrate ferrique administré par voie orale permet de corriger efficacement l’anémie en cas de carence martiale tout en exerçant un effet de chélation du phosphate. Le carboxymaltose ferrique permet l’administration intraveineuse de doses plus importantes de fer moins fréquemment. Le citrate de pyrophosphate ferrique administré directement via le dialysat autorise la compensation des pertes en fer en cours de séance d’hémodialyse (HD). Les inhibiteurs des HIF-prolyl-hydroxylase représentent une nouvelle classe thérapeutique d’agents stimulant l’érythropoïèse. Administrés par voie orale, ils agissent en stabilisant le facteur de transcription HIF impliqué dans l’initiation de la production d’érythropoïétine en situation d’hypoxie. Plusieurs études cliniques ont évalué ces nouvelles molécules en comparaison à un placebo ou aux EPO recombinantes. Chez les patients avec MRC non dialysés ou dialysés, ils ont montré leur non-infériorité par rapport aux érythropoïétines recombinantes pour corriger l’anémie. La diminution de l’hepcidine qu’ils induisent apparaît plus importante que celle induite par les EPO recombinantes injectables. Les premières données sur leur sécurité d’utilisation sont plutôt rassurantes mais devront être confirmées par des études à plus long terme et à plus larges effectifs.

© 2022 Publié par Elsevier Masson SAS au nom de Société francophone de néphrologie, dialyse et transplantation.

Anemia is a common complication of chronic kidney disease (CKD). The insufficient erythropoietin (EPO) production by the kidneys and iron deficiency are the main causes. Iron supplementation and the administration of recombinant EPO are the main treatment modalities. New iron formulations that can be administered orally, intravenously or directly via the dialysate have recently been developed to improve efficacy and tolerance. Ferric citrate administered orally can effectively corrects anemia in case of iron deficiency and in addition chelate phosphate in the gut lumen. Ferric carboxymaltose allows intravenous administration of larger doses given less frequently. Ferric pyrophosphate citrate administered directly via the dialysate allows the compensation of iron losses during the hemodialysis session. HIF-prolyl-hydroxylase inhibitors are a new therapeutic class of erythropoiesis-stimulating agents. Orally administered, they act by stabilizing the HIF transcription factor involved in the initiation of erythr