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Kidney transplantation (KT) is the best treatment for patients with kidney failure, associated with improved survival and quality of life compared with maintenance dialysis. However, despite constant improvements in the assessment and management of the alloimmune response, KT patients frequently demonstrate a reduced estimated glomerular filtration rate. Therefore, the usual complications of chronic kidney disease (CKD), such as anemia, hypertension, metabolic acidosis, hyperkalemia, or persistent secondary hyperparathyroidism, are highly prevalent after KT. However, their underlying mechanisms are different in the transplant setting (compared with the nontransplanted CKD population), and management recommendations are based on relatively poor-quality data. In recent years, new therapies have emerged, significantly improving kidney and cardiovascular outcomes of non-KT patients with CKD. Whether those new drugs could improve the outcomes of KT patients has largely been under investigated so far. In this review, we will address the challenges of the management of a KT patient with a reduced estimated glomerular filtration rate, cover the published evidence, and highlight the critical knowledge gaps., Competing Interests: T.D. reports research support from the Fonds National de Recherche Scientifique – FNRS (F.R.S.-FNRS) as well as travel support from Organ Recovery Systems, Diegem, Belgium. E.G. reports research support from Baxter Healthcare, conference support from Baxter Healthcare, Fresenius, Nx Stage, Dirinco, and AstraZeneca; and consulting fees from Amgen, Astellas, AstraZeneca, Bayer, Baxter Healthcare, Fresenius, NxStage, and Dirinco. M.J. reports research support from AstraZeneca, speaker fees from AstraZeneca, Bayer, Boehringer-Ingelheim, and Menarini; consulting fees from Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Cardiorenal, CSL Vifor, GlaxoSmithKline, Stada-Eurogenerics, and Vertex; and other: co-chair of Kidney Disease Improving Global Outcomes (KDIGO) since January 2019. A.D. reports consultancy fees from Alnylam and Merck. E.V.R. reports support from CSL Vifor and Pharmacosmos; speaker fees from Baxter Healthcare, Astellas, and Bayer; and consulting fees from Bayer. N.K. reports consulting fees from Hansa Biopharm. The other authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objective: Coronavirus Disease 2019 (COVID-19) has been associated with the onset of autoimmune conditions, but whether this relationship is causal remains unknown, partly because robust evidence based on the detection of autoantibodies is lacking. This study explored the potential impact of COVID-19 pandemic on the temporal trends of autoimmunity., Methods: Retrospective analysis of all consecutive autoimmune tests performed at one central laboratory at a University hospital, operating services for 18 other hospitals and clinical laboratories in Belgium, from January 01, 2015 to May 31, 2022. Longitudinal changes in the positivity rates of autoimmunity tests were analyzed, i.e. before and after the onset of the COVID-19 pandemic (March 11, 2020). The tests notably included the detection of autoantibodies associated with type 1 diabetes, thyroid diseases, connective tissue diseases, antiphospholipid syndrome, vasculitis and other organ-specific conditions. Kendall rank correlation test was applied to assess temporal trends., Results: Over a period of 89 months, a total of 301,720 consecutive tests for 24 different autoantibodies among 87,674 unique patients were performed (87% adults, 68% women, mean age 44 ± 20 years). Overall, 52,862 (18%) tests returned positive, with positivity rates for each test ranging between 1% and 46%. No increase in the positivity rate of autoimmunity tests was observed after the start of the pandemic., Conclusion: The onset of the COVID-19 pandemic was not associated with increased positivity rates of a large panel of autoimmune tests. Whether the higher incidence of autoimmune disorders associated with COVID-19 reflects detection bias or reverse causality, or is linked to seronegative autoimmune disorders requires further investigation., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E. Van Regemorter reports speaker honoraria for 10.13039/100004702Baxter and 10.13039/100004325AstraZeneca and travel grants from 10.13039/501100006484Vifor Pharma, Astellas and Pharmacosmos; all outside the submitted work. J. Morelle reports consultancy for Alexion Pharmaceuticals, AstraZeneca, Bayer, GlaxoSmithKline, and Sanofi-Genzyme; research funding from 10.13039/100006396Alexion Pharmaceuticals, 10.13039/100004325AstraZeneca, and 10.13039/100007658Baxter Healthcare; advisory or leadership roles for Alexion Pharmaceuticals, AstraZeneca, Bayer, Sanofi-Genzyme, and Versantis; speaker honoraria for 10.13039/100004325AstraZeneca, 10.13039/100007658Baxter Healthcare, and 10.13039/100015699Fresenius Medical Care; funding from the 10.13039/501100002661National Fund for Scientific Research (FRS-FNRS, Brussels, Belgium), the Association pour l’Information et la Recherche sur les Maladies Rénales Génétiques (AIRG, Brussels, Belgium), and the 10.13039/501100011068Saint-Luc Foundation (Brussels, Belgium); and travel grants from 10.13039/100013995Sanofi-Genzyme and 10.13039/501100006484Vifor Pharma; all outside the submitted work. All other authors do not report any conflict of interest., (© 2023 The Authors.)

Background: Early detection of hypertension in children with autosomal polycystic kidney disease (ADPKD) may be beneficial, but screening children at risk of ADPKD remains controversial. We investigated determinants of hypertension in children with ADPKD to help identify a subgroup of children at risk of ADPKD for whom screening for the disease and/or its complications would be more relevant., Methods: In a retrospective study including consecutive children with ADPKD aged 5-18 years and followed at Saint-Luc Hospital Brussels between 2006 and 2020, we investigated the potential association between genotype, clinical characteristics and parental phenotype, and presence of hypertension. Hypertension was defined as blood pressure > P95 during 24-h ambulatory monitoring or anti-hypertensive therapy use. Parental phenotype was considered severe based on age at kidney failure, Mayo Clinic Imaging Classification and rate of eGFR decline., Results: The study enrolled 55 children with ADPKD (mean age 9.9 ± 2.2 years, 45% male), including 44 with a PKD1 mutation and 5 with no mutation identified. Nine (16%) children had hypertension. Hypertension in children was associated with parental phenotype severity (8/27 (30%) children with severe parental phenotype vs. 1/23 (4%) children with non-severe parental phenotype (p = 0.03)) and height-adjusted bilateral nephromegaly (6/9 (67%) children with bilateral nephromegaly vs. 3/44 (7%) children without bilateral nephromegaly (p < 0.001))., Conclusions: Severe parental phenotype is associated with higher prevalence of hypertension in children with ADPKD. Hence, children of parents with severe ADPKD phenotype may be those who will most benefit from screening of the disease and/or yearly BP measures. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Autosomal dominant polycystic kidney disease (ADPKD) is mainly caused by mutations in PKD1 or PKD2 genes. Mosaicism is characterized by a post-zygotic mutation resulting in the presence of two or more populations of cells with different genotypes in an individual. Mosaicism of PKD1 , rarely identified by conventional Sanger sequencing, is more easily detected using next generation sequencing techniques (NGS). PKD1 mosaicism has classically been associated with either milder kidney disease, asymmetric kidney disease, and/or negative family history. We report the case of a patient presenting severe renal, hepatic, and vascular phenotype secondary to PKD1 mosaicism, with a surprisingly low percentage of mutant allele in the patient's kidney and liver tissue. We reviewed clinical presentations of reported cases of PKD1 mosaicism.

Background: Even though the clinical features of Graves' orbitopathy (GO) are well known, its exact pathogenesis remains controversial. The imbalance of redox homeostasis in the connective tissue could play a crucial role leading to an inflammatory state and edema of soft orbital tissues, thus contributing to orbital hypoxia and increase in hypoxia-inducible factor (HIF)-1α. This oxidative stress appears to target the orbital cells such as fibroblasts and also adipocytes. This study aims to explore which pathways can lead to the aforementioned oxidative stress in GO adipose cells and therefore offers new plausible therapeutic targets. Methods: Orbital fat samples were obtained from patients with GO (Western blot [WB]: n  = 8, immunohistochemistry [IHC]: n  = 8) and from control patients (WB: n  = 5, IHC: n  = 3-5). They were processed for WB analysis and IHC of the antioxidants (catalase, superoxide dismutase 1) and for HIF-1α. The expression of caveolin-1 (Cav-1) and deiodinase 3 (DIO3), known to be regulated by HIF-1α, was also analyzed by WB and IHC, as well as the targets of Cav-1: glucose transporter type 4 (Glut-4), NADPH oxidase (NOX)-2, and endothelial nitric oxide synthase (eNOS). Triiodothyronine (T3) expression was also analyzed by IHC. Results: In GO adipocytes, the expression of catalase was reduced, whereas that of HIF-1α was strongly increased. A decreased local T3 supply was associated with DIO3 upregulation. The low expression of Cav-1 in GO adipocytes was associated not only with low expression of Glut-4 but also with an increased expression of NOX-2 and active eNOS phosphorylated on serine 1177. Conclusions: Cav-1 and DIO3, both sensitive to hypoxia and to the increase of HIF-1α, play a pivotal role in the oxidative stress in GO adipocytes. DIO3 regulates the cellular supply of T3, which is essential for the cell homeostasis. Cav-1 determines the cellular glucose supply through Glut-4 and regulates the activity of NOX-2 generating superoxide anions and that of eNOS generating nitric oxide (NO).

Background: Graves' orbitopathy (GO) is the main extrathyroidal manifestation associated with Graves' disease (GD). It is characterized by reduced eye motility due to an increased volume of orbital fat and/or of extraocular muscles (EOMs) infiltrated by fibrosis and adipose tissue. The pathogenetic mechanisms leading to fibrosis and adipogenesis are mainly based on the interaction between orbital fibroblasts and immune cells (lymphocytes and mast cells) infiltrating the GO EOMs., Methods: Analysis of the morphological status, oxidative stress (OS), and antioxidant defenses in the orbital muscular cells and adipocytes in GO patients compared with controls was conducted., Results: Both cell types are affected by OS, as shown by the increased expression of 4-hydroxynonenal, which leads to apoptosis in muscular cells. However, the EOMs and the adipocytes possess antioxidant defenses (peroxiredoxin 5 and catalase) against the OS, which are also upregulated in thyrocytes in GD. The expression of adiponectin (ApN) and proliferator-activated receptor gamma (PPARγ) is also increased in GO muscular cells and adipocytes. OS and antioxidant proteins expression are correlated to the level of blood antithyrotropin receptor antibodies (TSHR-Ab)., Conclusion: Even when TSHR-Ab level is normalized, OS and antioxidant protein expression is high in EOM muscular cells and adipocytes in GO compared with controls. This justifies a supplementation with antioxidants in active as well as chronic GO patients. Orbital muscular cells are also the sources of PPARγ and ApN, which have direct or indirect local protective effects against OS. Modulation of these proteins could be considered as a future therapeutic approach for GO.