Exposure of human fetal kidneys to mild analgesics interferes with early nephrogenesis.

Acetaminophen, aspirin, and ibuprofen are mild analgesics commonly used by pregnant women, the sole current recommendation being to avoid ibuprofen from the fifth month of gestation. The nephrotoxicity of these three analgesics is well documented in adults, as is their interference with prostaglandins biosynthesis. Here we investigated the effect of these analgesics on human first trimester kidneys ex vivo. We first evaluated prostaglandins biosynthesis functionality by performing a wide screening of prostaglandin expression patterns in first trimester human kidneys. We demonstrated that prostaglandins biosynthesis machinery is functional during early nephrogenesis. Human fetal kidney explants aged 7-12 developmental weeks were exposed ex vivo to ibuprofen, aspirin or acetaminophen for 7 days, and analyzed by histology, immunohistochemistry, and flow cytometry. This study has revealed that these analgesics induced a spectrum of abnormalities within early developing structures, ranging from cell death to a decline in differentiating glomeruli density. These results warrant caution for the use of these medicines during the first trimester of pregnancy.

Among CMV-positive renal transplant patients receiving non-T-cell depleting induction, the absence of CMV disease prevention is a safe strategy: A retrospective cohort of 372 patients.

Cytomegalovirus (CMV) is the most common opportunistic pathogen affecting renal transplant recipients, especially in the first months. CMV-seropositive renal transplant recipients (CMV R+) are at intermediate risk for CMV disease, but this risk is enhanced among CMV R+ receiving T-cell depleting induction, compared to CMV R+ receiving non-depleting induction. In this second group, data in favor of prophylactic antiviral treatment with valganciclovir to reduce CMV disease is sparse. In this retrospective and multicentric trial, we included 372 CMV R+ transplanted between January 2012 and April 2015 and receiving non-depleting induction. During the first year following transplantation, CMV disease occurred in 5/222 patients (2.25%) in the prophylaxis group and 9/150 (6%) in the no-prophylaxis group (difference +3.7; 95% CI: 0.5-8; P = .002 for non-inferiority). The incidence of allograft rejection and other infectious diseases was similar between the two groups. Graft and patient survival were similar at the end of follow-up. In conclusion, the absence of prophylaxis did not appear to have a deleterious effect for CMV diseases among CMV R+ receiving non-depleting induction.

Fate of discarded kidney transplants: experience of the transplant university hospital center of Rennes / Devenir des greffons rénaux refusés : expérience du centre de transplantation du CHU de Rennes

Introduction: In a context of tension on the number of available kidney transplants compared to the number needed, the practices of refusal of transplants in the Rennes transplantation center were evaluated. Materials and methods: The donors completely refused by our team (no kidney accepted for any Rennes recipient) between January 1st 2012 and December 31st 2015 were identified from the national CRISTAL registry. The outcome of these refused transplants (possible transplantation in another center), the data of the recipients (from Rennes and other centers) and the data of the donors (refused and then finally accepted) were extracted. The outcome of recipients (from Rennes and other centers) was compared: graft survival (censored on death) and patient survival (not censored on cessation of function). The Kidney Donor Profile Index (KDPI) score was calculated and its usefulness studied. Results: Among the 203 rejected donors, 172 (85 %) were accepted for transplantation in another center; 89% of these grafts were functional at one year. In univariate analysis, Rennes recipients transplanted after a refusal had a better graft survival (censored on death) than recipients transplanted in another center with the refused graft (p < 0.001). The main limitation of this analysis is the non-comparability of the groups. The KDPI score was significantly associated with graft survival (censored on death). Of the 151 Rennes patients who had a refusal, 3% were still on the waiting list at the end of the observation period, the others spent a median additional time on dialysis of 220 days (Q1-Q3 81-483). Conclusion: Rennes recipients transplanted after a first refusal seem to have a better graft survival (censored on death) than recipients from other centers transplanted with refused grafts. This is to be weighed against the additional time on dialysis and even the risk of non-transplantation.

Introduction: Dans un contexte de tension sur le nombre de greffons rénaux disponibles comparé au nombre nécessaire, les pratiques de refus des greffons du centre de transplantation rennais ont été évaluées. Matériels et méthodes: À partir du registre national CRISTAL, les donneurs complètement refusés par notre équipe (aucun rein accepté pour aucun receveur rennais) entre le 1er janvier 2012 et le 31 décembre 2015 ont été identifiés. Le devenir de ces greffons refusés (éventuelle greffe dans un autre centre), les données des receveurs (rennais et des autres centres) et les données des donneurs (refusés puis finalement acceptés) ont été extraits. Le devenir des receveurs (rennais et des autres centres) a été comparé : survie du greffon (censurée sur le décès) et du patient (non censurée sur l'arrêt de fonction). Le score KDPI (Kidney Donor Profile Index) a été calculé et son intérêt étudié. Résultats: Parmi les 203 donneurs refusés, 172 (85 %) ont permis une transplantation dans un autre centre, dont 89 % de greffons fonctionnels à un an. En analyse univariée, les receveurs rennais greffés après un refus avaient une meilleure survie greffon (censurée sur le décès) que les receveurs greffés dans un autre centre avec le greffon refusé (p < 0,001). La principale limite de cette analyse est la non-comparabilité des groupes. Le score KDPI était significativement associé à la survie greffon (censurée sur le décès). Parmi les 151 patients rennais qui ont eu un refus, 3 % étaient toujours sur liste d'attente à l'issue de la période d'observation, les autres passaient un temps médian supplémentaire en dialyse de 220 jours (Q1-Q3 81-483). Conclusion: Les receveurs rennais greffés après un premier refus semblent avoir une meilleure survie du greffon (censurée sur le décès) que les receveurs des autres centres greffés avec les greffons refusés. C'est à mettre en balance avec le temps supplémentaire en dialyse, voire le risque de non-greffe.

Maternal, foetal and child consequences of immunosuppressive drugs during pregnancy in women with organ transplant: a review.

Although pregnancy remains exceptional in women after heart, liver or lung transplant, obstetricians and nephrologists are regularly confronted with pregnancy in renal transplant recipients. National and international registries have described the epidemiology of maternal, foetal and neonatal complications, and transplantation societies have published recommendations on the monitoring of these high-risk pregnancies. In this review, we summarize the existing data on maternal and foetal complications of pregnancies in women after renal transplant, especially the management of immunosuppression. We also describe the few available data on the middle- and long-term outcomes of their children who were exposed in utero to immunosuppressive drugs.