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1. Joint statement for assessing and managing high blood pressure in children and adolescents: Chapter 1. How to correctly measure blood pressure in children and adolescents

Author

Lurbe, E, Mancia, G, Calpe, J, Drozdz, D, Erdine, S, Fernandez-Aranda, F, Hadjipanayis, A, Hoyer, P, Jankauskiene, A, Jimenez-Murcia, S, Litwin, M, Mazur, A, Pall, D, Seeman, T, Sinha, M, Simonetti, G, Stabouli, S, Wuhl, E, Lurbe E., Mancia G., Calpe J., Drozdz D., Erdine S., Fernandez-Aranda F., Hadjipanayis A., Hoyer P. F., Jankauskiene A., Jimenez-Murcia S., Litwin M., Mazur A., Pall D., Seeman T., Sinha M. D., Simonetti G., Stabouli S., Wuhl E., Lurbe, E, Mancia, G, Calpe, J, Drozdz, D, Erdine, S, Fernandez-Aranda, F, Hadjipanayis, A, Hoyer, P, Jankauskiene, A, Jimenez-Murcia, S, Litwin, M, Mazur, A, Pall, D, Seeman, T, Sinha, M, Simonetti, G, Stabouli, S, Wuhl, E, Lurbe E., Mancia G., Calpe J., Drozdz D., Erdine S., Fernandez-Aranda F., Hadjipanayis A., Hoyer P. F., Jankauskiene A., Jimenez-Murcia S., Litwin M., Mazur A., Pall D., Seeman T., Sinha M. D., Simonetti G., Stabouli S., and Wuhl E.

Abstract

The joint statement is a synergistic action between HyperChildNET and the European Academy of Pediatrics about the diagnosis and management of hypertension in youth, based on the European Society of Hypertension Guidelines published in 2016 with the aim to improve its implementation. The first and most important requirement for the diagnosis and management of hypertension is an accurate measurement of office blood pressure that is currently recommended for screening, diagnosis, and management of high blood pressure in children and adolescents. Blood pressure levels should be screened in all children starting from the age of 3 years. In those children with risk factors for high blood pressure, it should be measured at each medical visit and may start before the age of 3 years. Twenty-four-hour ambulatory blood pressure monitoring is increasingly recognized as an important source of information as it can detect alterations in circadian and short-term blood pressure variations and identify specific phenotypes such as nocturnal hypertension or non-dipping pattern, morning blood pressure surge, white coat and masked hypertension with prognostic significance. At present, home BP measurements are generally regarded as useful and complementary to office and 24-h ambulatory blood pressure for the evaluation of the effectiveness and safety of antihypertensive treatment and furthermore remains more accessible in primary care than 24-h ambulatory blood pressure. A grading system of the clinical evidence is included.

Published
2023

2. Joint statement for assessing and managing high blood pressure in children and adolescents: Chapter 2. How to manage high blood pressure in children and adolescents

Author

Wuhl, E, Calpe, J, Drozdz, D, Erdine, S, Fernandez-Aranda, F, Hadjipanayis, A, Hoyer, P, Jankauskiene, A, Jimenez-Murcia, S, Litwin, M, Mancia, G, Mazur, A, Pall, D, Seeman, T, Sinha, M, Simonetti, G, Stabouli, S, Lurbe, E, Wuhl E., Calpe J., Drozdz D., Erdine S., Fernandez-Aranda F., Hadjipanayis A., Hoyer P. F., Jankauskiene A., Jimenez-Murcia S., Litwin M., Mancia G., Mazur A., Pall D., Seeman T., Sinha M. D., Simonetti G., Stabouli S., Lurbe E., Wuhl, E, Calpe, J, Drozdz, D, Erdine, S, Fernandez-Aranda, F, Hadjipanayis, A, Hoyer, P, Jankauskiene, A, Jimenez-Murcia, S, Litwin, M, Mancia, G, Mazur, A, Pall, D, Seeman, T, Sinha, M, Simonetti, G, Stabouli, S, Lurbe, E, Wuhl E., Calpe J., Drozdz D., Erdine S., Fernandez-Aranda F., Hadjipanayis A., Hoyer P. F., Jankauskiene A., Jimenez-Murcia S., Litwin M., Mancia G., Mazur A., Pall D., Seeman T., Sinha M. D., Simonetti G., Stabouli S., and Lurbe E.

Abstract

The joint statement is a synergistic action between HyperChildNET and the European Academy of Pediatrics about the diagnosis and management of hypertension in youth, based on the European Society of Hypertension Guidelines published in 2016 with the aim to improve its implementation. Arterial hypertension is not only the most important risk factor for cardiovascular morbidity and mortality, but also the most important modifiable risk factor. Early hypertension-mediated organ damage may already occur in childhood. The duration of existing hypertension plays an important role in risk assessment, and structural and functional organ changes may still be reversible or postponed with timely treatment. Therefore, appropriate therapy should be initiated in children as soon as the diagnosis of arterial hypertension has been confirmed and the risk factors for hypertension-mediated organ damage have been thoroughly evaluated. Lifestyle measures should be recommended in all hypertensive children and adolescents, including a healthy diet, regular exercise, and weight loss, if appropriate. If lifestyle changes in patients with primary hypertension do not result in normalization of blood pressure within six to twelve months or if secondary or symptomatic hypertension or hypertension-mediated organ damage is already present, pharmacologic therapy is required. Regular follow-up to assess blood pressure control and hypertension-mediated organ damage and to evaluate adherence and side effects of pharmacologic treatment is required. Timely multidisciplinary evaluation is recommended after the first suspicion of hypertension. A grading system of the clinical evidence is included.

Published
2023

3. HyperChildNET: A European Network Moving Forward in the Field of Pediatric Hypertension

Author

Lurbe, E, Mancia, G, Drozdz, D, Erdine, S, Fernandez-Aranda, F, Litwin, M, Sinha, M, Simonetti, G, Stabouli, S, Wuhl, E, Lurbe E., Mancia G., Drozdz D., Erdine S., Fernandez-Aranda F., Litwin M., Sinha M. D., Simonetti G., Stabouli S., Wuhl E., Lurbe, E, Mancia, G, Drozdz, D, Erdine, S, Fernandez-Aranda, F, Litwin, M, Sinha, M, Simonetti, G, Stabouli, S, Wuhl, E, Lurbe E., Mancia G., Drozdz D., Erdine S., Fernandez-Aranda F., Litwin M., Sinha M. D., Simonetti G., Stabouli S., and Wuhl E.

Published
2023

5. A Lifestyle Intervention in Pregnancy Prevents Maternal Obesity-Related Cardiac Remodelling in 3-Year-Old Children of UPBEAT RCT: A Case Control Study

Author

Taylor, Paul David, primary, Gu, Haotian, additional, Saunders, Hannah, additional, Fiori, Federico, additional, Dalrymple, Kathryn V., additional, Sethupathi, Priyanka, additional, Miller, Faith, additional, Jones, B, additional, Vieira, Matias Costa, additional, Singh, Claire, additional, Briley, Annette, additional, Seed, Paul, additional, Pasupathy, Dharmintra, additional, Santosh, Palmela J., additional, Groves, Alan M., additional, Sinha, M D, additional, Chowienczyk, Phillip J., additional, Poston, Lucilla, additional, and Consortium, UPBEAT, additional

Published
2020
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8. Biomarkers of tolerance in kidney transplantation - are we predicting tolerance or response to immunosuppressive treatment?

Author

Rebollo‐Mesa, I., Nova‐Lamperti, E., Mobillo, P., Runglall, M., Christakoudi, S., Norris, S., Smallcombe, N., Kamra, Y., Hilton, R., Bhandari, S., Baker, R., Berglund, D., Carr, S., Game, D., Griffin, S., Kalra, P. A., Lewis, R., Mark, P. B., Marks, S., Macphee, I., McKane, W., Mohaupt, M. G., Pararajasingam, R., Kon, S. P., Serón, D., Sinha, M. D., Tucker, B., Viklický, O., Lechler, R. I., Lord, G. M., and Hernandez‐Fuentes, M. P.

Subjects
Graft Rejection, Male, translational research/science, kidney transplantation/nephrology, Kidney Function Tests, OPERATIONAL TOLERANCE, Risk Factors, molecular biology, Prospective Studies, immunobiology, GENE-EXPRESSION, B-Lymphocytes, tolerance, Graft Survival, SIGNATURE, 11 Medical And Health Sciences, Middle Aged, Clinical Science, Prognosis, RENAL-TRANSPLANT, TNF-ALPHA, REJECTION, B-CELLS, biomarker, Female, Original Article, Transplantation Tolerance, Life Sciences & Biomedicine, Immunosuppressive Agents, Glomerular Filtration Rate, Adult, ALLOGRAFT, Indices of Tolerance EU Consortium, kidney (allograft) function/dysfunction, Immune Tolerance, Humans, Aged, Immunosuppression Therapy, Transplantation, Science & Technology, Original Articles, Kidney Transplantation, RECIPIENTS, Case-Control Studies, T-CELLS, Kidney Failure, Chronic, Surgery, Biomarkers, RD, Follow-Up Studies
Abstract

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell–related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group—namely, the tolerant recipients—were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS‐independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross‐validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management., The relationship between B cell gene expression and transplantation tolerance is confounded by the effects of immunosuppressive drugs, and correcting for this effect on gene expression is possible, exposing an equally accurate signature of tolerance. See page 3320 for Markmann's editorial.

Published
2016

9. Distributed expertise: qualitative study of a B ritish network of multidisciplinary teams supporting parents of children with chronic kidney disease

Author

Swallow, V., primary, Smith, T., additional, Webb, N. J. A., additional, Wirz, L., additional, Qizalbash, L., additional, Brennan, E., additional, Birch, A., additional, Sinha, M. D., additional, Krischock, L., additional, Voort, J., additional, King, D., additional, Lambert, H., additional, Milford, D. V., additional, Crowther, L., additional, Saleem, M., additional, Lunn, A., additional, and Williams, J., additional

Published
2014
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10. Underweight, overweight and obesity in paediatric dialysis and renal transplant patients

Author

Bonthuis, M., primary, van Stralen, K. J., additional, Verrina, E., additional, Groothoff, J. W., additional, Alonso Melgar, A., additional, Edefonti, A., additional, Fischbach, M., additional, Mendes, P., additional, Molchanova, E. A., additional, Paripovic, D., additional, Peco-Antic, A., additional, Printza, N., additional, Rees, L., additional, Rubik, J., additional, Stefanidis, C. J., additional, Sinha, M. D., additional, Zagozdzon, I., additional, Jager, K. J., additional, and Schaefer, F., additional

Published
2013
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11. Paediatric nephrology - A

Author

Okamoto, S., primary, Sakama, T., additional, Nakamura, S., additional, Niimura, F., additional, Sahin, S., additional, Ertan, P., additional, Evrengul, H., additional, Horasan, G., additional, Dede, B., additional, Berdeli, A., additional, Yildiz, N., additional, Cicek Deniz, N., additional, Asadov, R., additional, Yucelten, D., additional, Alpay, H., additional, Prado, G., additional, Schoeneman, M., additional, Mongia, A., additional, Paudyal, B., additional, Feygina, V., additional, Norin, A., additional, Hochman, D., additional, Tawadrous, H., additional, Bansilal, V., additional, Topaloglu, R., additional, Gulhan, B., additional, Bilginer, Y., additional, Celebi Tayfur, A., additional, Yildiz, C., additional, Ozaltin, F., additional, Duzova, A., additional, Ozen, S., additional, Aki, T., additional, Besbas, N., additional, Komaki, F., additional, Hamasaki, Y., additional, Ishikura, K., additional, Hamada, R., additional, Sakai, T., additional, Hataya, H., additional, Ogata, K., additional, Fukuzawa, R., additional, Ando, T., additional, Honda, M., additional, Malke, A., additional, Silska-Dittmar, M., additional, Soltysiak, J., additional, Blumczynski, A., additional, Ostalska-Nowicka, D., additional, Zachwieja, J., additional, Tabel, Y., additional, Oncul, M., additional, Elmas, A., additional, Kavaz, A., additional, Ozcakar, Z. B., additional, Bulum, B., additional, Ekim, M., additional, Yalcinkaya, F., additional, Prikhodina, L., additional, Turpitko, O., additional, Dlin, V., additional, Gheith, O., additional, Alotaibi, T., additional, Nampoory, N., additional, Mosaad, A., additional, Halim, M., additional, Saied, T., additional, Abou Ateya, H., additional, Adel, H., additional, Mozarei, I., additional, Neir, P., additional, Uemura, O., additional, Ito, S., additional, Wada, N., additional, Hattori, M., additional, Ohashi, Y., additional, Tanaka, R., additional, Nakanishi, K., additional, Kaneko, T., additional, Golovachova, V., additional, Odinets, Y., additional, Laszki-Szczachor, K., additional, Polak-Jonkisz, D., additional, Sobieszczanska, M., additional, Rusiecki, L., additional, Zwolinska, D., additional, Ninchoji, T., additional, Kaitoh, H., additional, Matsunoshita, N., additional, Nozu, K., additional, Yoshikawa, N., additional, Iijima, K., additional, Maglalang-Reed, O. M., additional, Elises, J. S., additional, Zamora, M. N. V., additional, Pasco, P., additional, Arejola-Tan, A., additional, Alparslan, C., additional, Dogan, S. M., additional, Kose, E., additional, Elmas, C., additional, Kilinc, S., additional, Arslan, N., additional, Kebabci, E., additional, Karaca, C., additional, Yavascan, O., additional, Aksu, N., additional, Minson, S., additional, Munoz, M., additional, Vergara, I., additional, Mraz, M., additional, Vaughan, R., additional, Rees, L., additional, Olsburgh, J., additional, Calder, F., additional, Shroff, R., additional, Zaicova, N., additional, Lavrenchuk, O., additional, Viktoria, D., additional, Savchenko, V., additional, Bagdasarova, I., additional, Doyon, A., additional, Bayazit, A., additional, Canpolat, N., additional, Kracht, D., additional, Litwin, M., additional, Ranchin, B., additional, Sozeri, B., additional, Wuhl, E., additional, Zeller, R., additional, Melk, A., additional, Querfeld, U., additional, Schaefer, F., additional, Sinha, M. D., additional, Turner, C., additional, Booth, C. J., additional, Goldsmith, D. J. A., additional, and Simpson, J. M., additional

Published
2013
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14. Paediatric nephrology

Author

Shi, H., primary, Wen, J., additional, LI, Z., additional, Elsayed, M., additional, Kamal, K., additional, Shi, H., additional, El Shal, A., additional, Youssef, D., additional, Caubet, C., additional, Lacroix, C., additional, Benjamin, B., additional, Bandin, F., additional, Bascands, J.-L., additional, Monsarrat, B., additional, Decramer, S., additional, Schanstra, J., additional, Laetitia, D.-B., additional, Ulinski, T., additional, Aoun, B., additional, Ozdemir, K., additional, Dincel, N., additional, Sozeri, B., additional, Mir, S., additional, Berdeli, A., additional, Akyigit, F., additional, Mizerska-Wasiak, M., additional, Panczyk-Tomaszewska, M., additional, Szymanik-Grzelak, H., additional, Roszkowska-Blaim, M., additional, Jamin, A., additional, Dehoux, L., additional, Monteiro, R. C., additional, Deschenes, G., additional, Bouts, A., additional, Davin, J.-C., additional, Dorresteijn, E., additional, Schreuder, M., additional, Lilien, M., additional, Oosterveld, M., additional, Kramer, S., additional, Gruppen, M., additional, Pintos-Morell, G., additional, Ramaswami, U., additional, Parini, R., additional, Rohrbach, M., additional, Kalkum, G., additional, Beck, M., additional, Carter, M., additional, Antwi, S., additional, Callegari, J., additional, Kotanko, P., additional, Levin, N. W., additional, Rumjon, A., additional, Macdougall, I. C., additional, Turner, C., additional, Booth, C. J., additional, Goldsmith, D., additional, Sinha, M. D., additional, Camilla, R., additional, Loiacono, E., additional, Donadio, M. E., additional, Conrieri, M., additional, Bianciotto, M., additional, Bosetti, F. M., additional, Peruzzi, L., additional, Conti, G., additional, Bitto, A., additional, Amore, A., additional, Coppo, R., additional, Maldyk, J., additional, Chou, H.-H., additional, Chiou, Y.-Y., additional, Bochniewska, V., additional, Jobs, K., additional, Jung, A., additional, Fallahzadeh Abarghooei, M. H., additional, Zare, J., additional, Sedighi Goorabi, V., additional, Derakhshan, A., additional, Basiratnia, M., additional, Fallahzadeh Abarghooei, M. A., additional, Hosseini Al-Hashemi, G., additional, Fallahzadeh Abarghooei, F., additional, Kluska-Jozwiak, A., additional, Soltysiak, J., additional, Lipkowska, K., additional, Silska, M., additional, Fichna, P., additional, Skowronska, B., additional, Stankiewicz, W., additional, Ostalska-Nowicka, D., additional, Zachwieja, J., additional, Girisgen, L., additional, Sonmez, F., additional, Yenisey, C., additional, Kis, E., additional, Cseprekal, O., additional, Kerti, A., additional, Szabo, A., additional, Salvi, P., additional, Benetos, A., additional, Tulassay, T., additional, Reusz, G., additional, Makulska, I., additional, Szczepanska, M., additional, Drozdz, D., additional, Zwolnska, D., additional, Tolstova, E., additional, Anis, L., additional, Alber, B., additional, Edouard, B., additional, Gerard, C., additional, Seni, K., additional, Dunia Julienne Hadiza, T., additional, Christian, S., additional, Benoit, T., additional, Francois, B., additional, Adama, L., additional, Rosenberg, A., additional, Munro, J., additional, Murray, K., additional, Wainstein, B., additional, Ziegler, J., additional, Singh-Grewal, D., additional, Boros, C., additional, Adib, N., additional, Elliot, E., additional, Fahy, R., additional, Mackie, F., additional, Kainer, G., additional, Polak-Jonkisz, D., additional, Zwolinska, D., additional, Laszki-Szczachor, K., additional, Janocha, A., additional, Rusiecki, L., additional, Sobieszczanska, M., additional, Garzotto, F., additional, Ricci, Z., additional, Clementi, A., additional, Cena, R., additional, Kim, J. C., additional, Zanella, M., additional, Ronco, C., additional, Purzyc, L., additional, Peco-Antic, A., additional, Kotur-Stevuljevic, J., additional, Paripovic, D., additional, Scekic, G., additional, Milosevski-Lomic, G., additional, Bogicevic, D., additional, Spasojevic-Dimitrijeva, B., additional, Hassan, R., additional, El-Husseini, A., additional, Sobh, M., additional, Ghoneim, M., additional, Harambat, J., additional, Bonthuis, M., additional, Van Stralen, K. J., additional, Ariceta, G., additional, Battelino, N., additional, Jahnukainen, T., additional, Sandes, A. R., additional, Combe, C., additional, Jager, K. J., additional, Verrina, E., additional, Schaefer, F., additional, Espindola, R., additional, Bacchetta, J., additional, Cochat, P., additional, Stefanis, C., additional, Leroy, S., additional, Fernandez-Lopez, A., additional, Nikfar, R., additional, Romanello, C., additional, Bouissou, F., additional, Gervaix, A., additional, Gurgoze, M., additional, Bressan, S., additional, Smolkin, V., additional, Tuerlinkx, D., additional, Stefanidis, C., additional, Vaos, G., additional, Leblond, P., additional, Gungor, F., additional, Gendrel, D., additional, Chalumeau, M., additional, Rawlins, D., additional, Simpson, J. M., additional, Arnaud, G., additional, Anne, M., additional, Stephanie, T., additional, Flavio, B., additional, Veronique, F. B., additional, Stephane, D., additional, Mumford, L., additional, Marks, S., additional, Ahmad, N., additional, Maxwell, H., additional, Tizard, J., additional, Vidal, E., additional, Amigoni, A., additional, Varagnolo, M., additional, Benetti, E., additional, Ghirardo, G., additional, Brugnolaro, V., additional, Murer, L., additional, Christine, G., additional, Degi, A., additional, Szabo, A. J., additional, Reusz, G. S., additional, Vidoni, A., additional, Ramondo, G., additional, and Miotto, D., additional

Published
2012
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17. Prophylactic Ureteric Stents in Renal Transplant Recipients: A Multicenter Randomized Controlled Trial of Early Versus Late Removal

Author

Patel, P., Rebollo‐Mesa, I., Ryan, E., Sinha, M. D., Marks, S. D., Banga, N., Macdougall, I. C., Webb, M. C., Koffman, G., and Olsburgh, J.

Abstract

Prophylactic ureteric stenting in renal transplantation reduces major urological complications; however, morbidity is related to the indwelling duration of a stent. We aimed to determine the optimal duration for stents in this clinical setting. Patients (aged 2–75 years) from six UKhospitals who were undergoing renal transplantation were recruited and randomly assigned to either early stent removal at 5 days (without cystoscopy) or late removal at 6 weeks after transplantation (with cystoscopy). The primary outcome was a composite of stent‐related complications defined as pain, visible hematuria, migration, fragmentation, and urinary tract infections (UTIs) within 3 mo of transplantation. Between May 2010 and Nov 2013, we randomly assigned 227 participants, with 205 included in the final analysis of the primary outcome. Stent‐related complications were significantly higher in the late versus early stent removal groups (36 of 126 [28.6%] vs. 6 of 79 [7.6%]; p < 0.001). The majority of stent complications consisted of UTIs, with an incidence of 31 of 126 (24.6%) in the late group compared with 6 of 79 (7.6%) in the early group (p = 0.004). We found early stent removal on day 5 significantly reduced stent‐related complications and improved quality of life in the first 3 mo after transplantation (ISRCTN09184595). In this randomized controlled trial, the authors determine that early prophylactic stent removal in renal transplant recipients at 5 days is beneficial, in terms of stent‐related complications and quality of life, compared to stent removal at 6 weeks.

Published
2017
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19. CKD / Mineral bone disease

Author

Goto, S., primary, Fujii, H., additional, Kono, K., additional, Nakai, K., additional, Hamada, Y., additional, Yamato, H., additional, Shinohara, M., additional, Kitazawa, R., additional, Kitazawa, S., additional, Nishi, S., additional, Fukagawa, M., additional, Stevens, K., additional, Beattie, E., additional, Sands, W., additional, Delles, C., additional, Jardine, A., additional, Masai, H., additional, Joki, N., additional, Kunimasa, T., additional, Furuhashi, T., additional, Fukuda, H., additional, Sugi, K., additional, Moroi, M., additional, Sinha, M. D., additional, Turner, C., additional, Dalton, R. N., additional, Rasmussen, P., additional, Waller, S., additional, Booth, C. J., additional, Goldsmith, D. J., additional, Van Zuilen, A., additional, Blankestijn, P., additional, Van Buren, M., additional, Ten Dam, M., additional, Kaasjager, H., additional, Ligtenberg, G., additional, Sijpkens, Y., additional, Sluiter, H., additional, Van de Ven, P., additional, Vervoort, G., additional, Vleming, L., additional, Bots, M., additional, and Wetzels, J., additional

Published
2011
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28. Exploring the relevance of NUP93 variants in steroid-resistant nephrotic syndrome using next generation sequencing and a fly kidney model.

Author

Bierzynska, A., Bull, K., Miellet, S., Dean, P., Neal, C., Colby, E., McCarthy, H. J., Hegde, S., Sinha, M. D., Bugarin Diz, C., Stirrups, K., Megy, K., Mapeta, R., Penkett, C., Marsh, S., Forrester, N., Afzal, M., Stark, H., BioResource, N., Williams, M., Welsh, G. I., Koziell, A. B., Hartley, Paul S., Saleem, M. A., Bierzynska, A., Bull, K., Miellet, S., Dean, P., Neal, C., Colby, E., McCarthy, H. J., Hegde, S., Sinha, M. D., Bugarin Diz, C., Stirrups, K., Megy, K., Mapeta, R., Penkett, C., Marsh, S., Forrester, N., Afzal, M., Stark, H., BioResource, N., Williams, M., Welsh, G. I., Koziell, A. B., Hartley, Paul S., and Saleem, M. A.

Abstract

BACKGROUND: Variants in genes encoding nuclear pore complex (NPC) proteins are a newly identified cause of paediatric steroid-resistant nephrotic syndrome (SRNS). Recent reports describing NUP93 variants suggest these could be a significant cause of paediatric onset SRNS. We report NUP93 cases in the UK and demonstrate in vivo functional effects of Nup93 depletion in a fly (Drosophila melanogaster) nephrocyte model. METHODS: Three hundred thirty-seven paediatric SRNS patients from the National cohort of patients with Nephrotic Syndrome (NephroS) were whole exome and/or whole genome sequenced. Patients were screened for over 70 genes known to be associated with Nephrotic Syndrome (NS). D. melanogaster Nup93 knockdown was achieved by RNA interference using nephrocyte-restricted drivers. RESULTS: Six novel homozygous and compound heterozygous NUP93 variants were detected in 3 sporadic and 2 familial paediatric onset SRNS characterised histologically by focal segmental glomerulosclerosis (FSGS) and progressing to kidney failure by 12 months from clinical diagnosis. Silencing of the two orthologs of human NUP93 expressed in D. melanogaster, Nup93-1, and Nup93-2 resulted in significant signal reduction of up to 82% in adult pericardial nephrocytes with concomitant disruption of NPC protein expression. Additionally, nephrocyte morphology was highly abnormal in Nup93-1 and Nup93-2 silenced flies surviving to adulthood. CONCLUSION: We expand the spectrum of NUP93 variants detected in paediatric onset SRNS and demonstrate its incidence within a national cohort. Silencing of either D. melanogaster Nup93 ortholog caused a severe nephrocyte phenotype, signaling an important role for the nucleoporin complex in podocyte biology. A higher resolution version of the Graphical abstract is available as Supplementary information.

29. HyperChildNET COST Action CA19115: report of the task force.

Author

Lurbe E, Mancia G, Drozdz D, Erdine S, Fernandez-Aranda F, Litwin M, Sinha MD, Simonetti G, Stabouli S, and Wühl E

Subjects
Humans, Adolescent, Child, Advisory Committees, Cardiovascular Diseases, Europe, Hypertension
Abstract

Purpose: Despite dramatic medical advances over the last few decades, cardiovascular disease remains a leading cause of death globally. High BP is clearly established, but modifiable, risk factor for early disability and death. Although most of the adverse outcomes occur in adulthood it has become clear that high BP is a life course problem that can become evident in early life however, relatively little attention has been paid to the problem of high BP in children and adolescents. Materials and methods: Being aware of the problem and the needs, the Task Force of the ESH Guidelines in children and adolescents took the initiative to move forward in the field, identifying the COST Action program. A proposal, HyperChildNET, was submitted, approved and funded for 4 years starting in October 2020. Results: The aim of the Action has been to establish a European sustainable and multidisciplinary network of researchers, clinicians, early career investigators, health economists, decision-makers, regulatory bodies, and medical devices manufacturers under the umbrella of the European Commission in order to acquire a holistic understanding of those factors affecting high BP in children and adolescents in order to propose and implement preventive and corrective actions. All the activities carried out during the 4 years are described. Conclusions: HyperChildNET offers a European perspective of the issue giving us the opportunity to develop new strategies and objectives moving forward in the field.

Published
2024
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30. Biomarkers of Tolerance in Kidney Transplantation: Are We Predicting Tolerance or Response to Immunosuppressive Treatment?

Author

Rebollo-Mesa I, Nova-Lamperti E, Mobillo P, Runglall M, Christakoudi S, Norris S, Smallcombe N, Kamra Y, Hilton R, Bhandari S, Baker R, Berglund D, Carr S, Game D, Griffin S, Kalra PA, Lewis R, Mark PB, Marks S, Macphee I, McKane W, Mohaupt MG, Pararajasingam R, Kon SP, Serón D, Sinha MD, Tucker B, Viklický O, Lechler RI, Lord GM, and Hernandez-Fuentes MP

Subjects
Adult, Aged, B-Lymphocytes drug effects, B-Lymphocytes immunology, B-Lymphocytes metabolism, Case-Control Studies, Female, Follow-Up Studies, Glomerular Filtration Rate, Graft Rejection drug therapy, Graft Rejection etiology, Graft Rejection metabolism, Graft Survival drug effects, Humans, Immune Tolerance drug effects, Kidney Failure, Chronic complications, Kidney Failure, Chronic surgery, Kidney Function Tests, Male, Middle Aged, Prognosis, Prospective Studies, Risk Factors, Biomarkers metabolism, Graft Rejection diagnosis, Graft Survival immunology, Immune Tolerance immunology, Immunosuppressive Agents therapeutic use, Kidney Transplantation adverse effects
Abstract

We and others have previously described signatures of tolerance in kidney transplantation showing the differential expression of B cell-related genes and the relative expansions of B cell subsets. However, in all of these studies, the index group-namely, the tolerant recipients-were not receiving immunosuppression (IS) treatment, unlike the rest of the comparator groups. We aimed to assess the confounding effect of these regimens and develop a novel IS-independent signature of tolerance. Analyzing gene expression in three independent kidney transplant patient cohorts (232 recipients and 14 tolerant patients), we have established that the expression of the previously reported signature was biased by IS regimens, which also influenced transitional B cells. We have defined and validated a new gene expression signature that is independent of drug effects and also differentiates tolerant patients from healthy controls (cross-validated area under the receiver operating characteristic curve [AUC] = 0.81). In a prospective cohort, we have demonstrated that the new signature remained stable before and after steroid withdrawal. In addition, we report on a validated and highly accurate gene expression signature that can be reliably used to identify patients suitable for IS reduction (approximately 12% of stable patients), irrespective of the IS drugs they are receiving. Only a similar approach will make the conduct of pilot clinical trials for IS minimization safe and hence allow critical improvements in kidney posttransplant management., (© 2016 The Authors. American Journal of Transplantation published by Wiley Periodicals, Inc. on behalf of American Society of Transplant Surgeons.)

Published
2016
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31. Mitochondrial disorders and general anaesthesia: a case series and review.

Author

Footitt EJ, Sinha MD, Raiman JA, Dhawan A, Moganasundram S, and Champion MP

Subjects
Adolescent, Anesthesia, General methods, Biopsy, Child, Child, Preschool, Female, Humans, Infant, Infant, Newborn, Male, Mitochondrial Diseases diagnosis, Mitochondrial Diseases pathology, Postoperative Complications, Retrospective Studies, Anesthesia, General adverse effects, Mitochondrial Diseases complications
Abstract

Patients with mitochondrial disease are at risk of metabolic decompensation and often require general anaesthesia (GA) as part of their diagnostic work up and subsequent management. However, the evidence base for the use of GA is limited and inconclusive. We have documented the practice and outcome in the use of GA in paediatric patients with mitochondrial disease using a retrospective case review study of 38 mitochondrial patients who had undergone 58 anaesthetics within the regional metabolic service for the period 1989-2005. A variety of anaesthetic agents were used and the pattern of use reflects that seen in standard paediatric practice. There were no episodes of malignant hyperthermia and no documented intraoperative events attributable to the GA. Three postoperative adverse events were noted; one episode of hypovolaemia, one episode of acute on chronic renal failure, and one episode of metabolic decompensation 12 h post-muscle biopsy. Despite theoretical concern about this group of patients, adverse events after GA are rare and in most cases unrelated to the anaesthesia. Further prospective studies of GA in mitochondrial disease are required to create evidence-based clinical guidelines for safe practice.

Published
2008
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