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Consensus on definition and severity grading of lymphatic complications after kidney transplantation
(2020)
Mehrabi, Arianeb ; Kulu, Yakup ; Sabagh, Mohammad Sadegh ; Khajeh, Elias ; Mohammadi, Sara ; Ghamarnejad, Omid ; Golriz, Mohammad ; Morath, Christian ; Bechstein, Wolf Otto ; Berlakovich, Gabriela A. ; Demartines, Nicolas ; Duran, Mansur ; Fischer, Lutz ; Gürke, Lorenz ; Klempnauer, Jürgen ; Königsrainer, Alfred ; Lang, Hauke ; Neumann, Ulf Peter ; Pasche, Andreas ; Paul, Andreas ; Pisarski, Przemyslaw ; Pratschke, Johann ; Schneeberger, Stefan ; Settmacher, Utz ; Viebahn, Richard ; Wirt, Manfred ; Wullich, Bernd ; Zeier, Martin ; Büchler, Markus W.
Background: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy.
Methods: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres.
Results: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention.
Conclusion: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.
Mateus Fernández, Sara ; Holló, Zsolt ; Kern, Andras ; Bakos, Éva ; Fischer, Paul A. ; Borst, Piet ; Evers, Raymond
In polarized cells, the multidrug resistance protein MRP2 is localized in the apical plasma membrane, whereas MRP1, another multidrug resistance protein (MRP) family member, is localized in the basolateral membrane. MRP1 and MRP2 are thought to contain an N-terminal region of five transmembrane segments (TMD0) coupled to 2 times six transmembrane segments via an intracellular loop (L0). We previously demonstrated for MRP1 that a mutant lacking TMD0 but still containing L0, called L0ΔMRP1, was functional and routed to the lateral plasma membrane. To investigate the role of the TMD0L0 region of MRP2 in routing to the apical membrane, we generated mutants similar to those made for MRP1. In contrast to L0ΔMRP1, L0ΔMRP2 was associated with an intracellular compartment, most likely endosomes. Co-expression with TMD0, however, resulted in apical localization of L0ΔMRP2 and transport activity. Uptake experiments with vesicles containing L0ΔMRP2 demonstrated that the molecule is able to transport LTC4. An MRP2 mutant without TMD0L0, ΔMRP2, was only core-glycosylated and localized intracellularly. Co-expression of ΔMRP2 with TMD0L0 resulted in an increased protein level of ΔMRP2, full glycosylation of the protein, routing to the apical membrane, and transport activity. Our results suggest that the TMD0 region is required for routing to or stable association with the apical membrane.
Forstner, Andreas Josef ; Hecker, Julian ; Hofmann, Andrea ; Maaser, Anna ; Reinbold, Céline S. ; Mühleisen, Thomas W. ; Leber, Markus ; Strohmaier, Jana ; Degenhardt, Franziska ; Treutlein, Jens ; Mattheisen, Manuel ; Schumacher, Johannes ; Streit, Fabian ; Meier, Sandra ; Herms, Stefan ; Hoffmann, Per ; Lacour, André ; Witt, Stephanie ; Reif, Andreas ; Müller-Myhsok, Bertram ; Lucae, Susanne ; Maier, Wolfgang ; Schwarz, Markus ; Vedder, Helmut ; Kammerer-Ciernioch, Jutta ; Pfennig, Andrea ; Bauer, Michael ; Hautzinger, Martin ; Moebus, Susanne ; Schenk, Lorena M. ; Fischer, Sascha B. ; Sivalingam, Sugirthan ; Czerski, Piotr M. ; Hauser, Joanna ; Lissowska, Jolanta ; Szeszenia-Dabrowska, Neonila ; Brennan, Paul E. ; McKay, James D. ; Wright, Adam ; Mitchell, Philip B. ; Fullerton, Janice M. ; Schofield, Peter R. ; Montgomery, Grant W. ; Medland, Sarah E. ; Gordon, Scott D. ; Martin, Nicholas Gordon ; Krasnov, Valery ; Chuchalin, Alexander ; Babadjanova, Gulja ; Pantelejeva, Galina ; Abramova, Lilia I. ; Tiganov, Alexander S. ; Polonikov, Alexey ; Khusnutdinova, Elza ; Alda, Martin ; Cruceanu, Cristiana ; Rouleau, Guy A. ; Turecki, Gustavo ; Laprise, Catherine ; Rivas, Fabio ; Mayoral, Fermı́n ; Kogevinas, Manolis ; Grigoroiu-Serbanescu, Maria ; Becker, Tim ; Schulze, Thomas Gerd ; Rietschel, Marcella ; Cichon, Sven ; Fier, Heide ; Nöthen, Markus Maria
Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.