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4. Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Author

Gharavi, Ali, Ahn, Wooin, Appel, Gerald B., Avasare, Rupali S., Babayev, Revekka, Batal, Ibrahim, Bomback, Andrew S., Brown, Eric, Campenot, Eric S., Canetta, Pietro, Chan, Brenda, D’Agati, Vivette D., Fernandez, Hilda, Foroncewicz, Bartosz, Ghiggeri, Gian Marco, Hines, William H., Jain, Namrata G., Kiryluk, Krzysztof, Lin, Fangming, Lugani, Francesca, Marasa, Maddalena, Markowitz, Glen, Mohan, Sumit, Mucha, Krzysztof, Nickolas, Thomas L., Radhakrishnan, Jai, Rao, Maya K., Regunathan-Shenk, Renu, Sanna-Cherchi, Simone, Santoriello, Dominick, Stokes, Michael B., Yu, Natalie, Valeri, Anthony M., Zviti, Ronald, Greenbaum, Larry A., Smoyer, William E., Al-Uzri, Amira, Ashoor, Isa, Aviles, Diego, Baracco, Rossana, Barcia, John, Bartosh, Sharon, Belsha, Craig, Braun, Michael C., Chishti, Aftab, Claes, Donna, Cramer, Carl, Davis, Keefe, Erkan, Elif, Feig, Daniel, Freundlich, Michael, Hanna, Melisha, Hidalgo, Guillermo, Jain, Amrish, Khalid, Myda, Kallash, Mahmoud, Lane, Jerome C., Mahan, John, Mathews, Nisha, Nester, Carla, Pan, Cynthia, Patel, Hiren, Revell, Adelaide, Sreedharan, Rajasree, Steinke, Julia, Wenderfer, Scott E., Wong, Craig S., Falk, Ronald, Cook, William, Derebail, Vimal, Fogo, Agnes, Gasim, Adil, Gehr, Todd, Harris, Raymond, Kidd, Jason, Laurin, Louis-Philippe, Pendergraft, Will, Pichette, Vincent, Powell, Thomas Brian, Renfrow, Matthew B., Royal, Virginie, Holzman, Lawrence B., Adler, Sharon, Alpers, Charles, Matar, Raed Bou, Brown, Elizabeth, Cattran, Daniel, Choi, Michael, Dell, Katherine M., Dukkipati, Ram, Fervenza, Fernando C., Fornoni, Alessia, Gadegbeku, Crystal, Gipson, Patrick, Hasely, Leah, Hingorani, Sangeeta, Hladunewich, Michelle A., Hogan, Jonathan, Jefferson, J. Ashley, Jhaveri, Kenar, Johnstone, Duncan B., Kaskel, Frederick, Kogan, Amy, Kopp, Jeffrey, Lemley, Kevin V., Dieguez, Laura Malaga, Meyers, Kevin, Neu, Alicia, O’Shaughnessy, Michelle Marie, O’Toole, John F., Parekh, Rulan, Reich, Heather, Reidy, Kimberly, Rondon, Helbert, Sambandam, Kamalanathan K., Sedor, John R., Selewski, David T., Sethna, Christine B., Schelling, Jeffrey, Sperati, C. John, Swiatecka-Urban, Agnes, Trachtman, Howard, Tuttle, Katherine R., Weisstuch, Joseph, Zhdanova, Olga, Gillespie, Brenda, Gipson, Debbie S., Kretzler, Matthias, Robinson, Bruce M., Barisoni, Laura, Mansfield, Sarah, Mariani, Laura, Nast, Cynthia C., Wladkowski, Matthew, Zee, Jarcy, Guay-Woodford, Lisa M., Ambruzs, Josephine M., Cai, Yi, Cattran, Daniel C., Chishti, Aftab S., D'Agati, Vivette D., D'Alessandri-Silva, Cynthia J., Gbadegesin, Rasheed A., Hogan, Jonathan J., Iragorri, Sandra, Jennette, J. Charles, Julian, Bruce A., Lafayette, Richard A., Liapis, Helen, Mansfield, Sarah A., Mason, Sherene, Nachman, Patrick H., Nester, Carla M., Noone, Damien G., Novak, Jan, O'Shaughnessy, Michelle M., Reich, Heather N., Rheault, Michelle N., Rizk, Dana V., Saha, Manish K., Sanghani, Neil S., Srivastava, Tarak, Swiatecka-Urban, Agnieszka, Twombley, Katherine, Vasylyeva, Tetyana L., Weaver, Donald J., Yin, Hong, Falk, Ronald J., Gharavi, Ali G., Gillespie, Brenda W., and Flessner, Michael

Published
2018
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8. The role of von Willebrand factor in thrombotic microangiopathy

Author

Noone, Damien G., Riedl, Magdalena, and Licht, Christoph

Subjects
Research, Causes of, Thrombosis -- Causes of -- Research, Endothelium -- Research, Von Willebrand factor -- Research, Thrombocytopenic purpura -- Research
Abstract

Author(s): Damien G. Noone [sup.1] [sup.2] , Magdalena Riedl [sup.3] , Christoph Licht [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] Author Affiliations: (Aff1) 0000 0004 0473 9646, grid.42327.30, Division of Nephrology, The [...], Thrombotic microangiopathy (TMA) is caused by thrombus formation in the microvasculature. The disease spectrum of TMA includes, amongst others, thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS). TTP is caused by defective cleavage of von Willebrand factor (VWF), whereas aHUS is caused by overshooting complement activation and subsequent endothelial cell (EC) injury. Despite their distinct pathophysiology, the clinical manifestation of TTP and aHUS consisting of microangiopathic haemolytic anaemia and thrombocytopenia is often similar and difficult to distinguish. Recent evidence hints at both a genetic and functional link between TTP and aHUS, especially between VWF and the complement system. There is novel in vitro evidence that complement activation not only results in VWF release from ECs, but that VWF also functions as a negative complement regulator, thus protecting the EC surface from ongoing complement attack. Although contrary to previous experimental work suggesting that complement can be activated on VWF multimers, there may be an explanation in vivo that rationalizes these apparently contradictory findings, whereby a system primarily meant to regulate becomes overwhelmed or pathologic in the disease state. The importance of unravelling these recent findings for our understanding of TMA pathology becomes even more evident considering that glomerular ECs express VWF in a heterogeneous pattern with an overall decreased expression level, thus potentially leaving the glomerular ECs vulnerable to complement-mediated injury. Taken together, these findings support the concept that TTP and aHUS represent two extreme ends of a TMA disease spectrum rather than isolated disease entities.

Published
2018
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10. Von Willebrand factor regulates complement on endothelial cells

Author

Noone, Damien G., Riedl, Magdalena, Pluthero, Fred G., Bowman, Mackenzie L., Liszewski, M. Kathryn, Lu, Lily, Quan, Yi, Balgobin, Steve, Schneppenheim, Reinhard, Schneppenheim, Sonja, Budde, Ulrich, James, Paula, Atkinson, John P., Palaniyar, Nades, Kahr, Walter H.A., and Licht, Christoph

Published
2016
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15. Implementing a fluid volume management program to decrease intra-dialytic hypotensive events in a paediatric in-centre haemodialysis unit: a quality improvement project

Author

Snauwaert, Evelien, primary, Wagner, Stéphanie, additional, Jawa, Natasha A., additional, Bruno, Valentina, additional, McKay, Ashlene, additional, Kirpalani, Amrit, additional, Nemec, Rosaleen, additional, Teoh, Chia Wei, additional, Harvey, Elizabeth A., additional, Zappitelli, Michael, additional, Licht, Christoph, additional, and Noone, Damien G., additional

Published
2021
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17. Wide variation in glucocorticoid dosing in paediatric ANCA-associated vasculitis with renal disease: a paediatric vasculitis initiative study

Author

Chen, Audrea, primary, Mammen, Cherry, additional, Guzman, Jaime, additional, Al-Abadi, Eslam, additional, Benseler, Susanne M., additional, Berard, Roberta A., additional, Gerstbacher, Dana, additional, Heshin-Bekenstein, Merav, additional, Kim, Susan, additional, Klein-Gitelman, Marisa, additional, Chavan, Pallavi Pimpale, additional, James, Karen E., additional, Martin, Neil, additional, McErlane, Flora, additional, Myrup, Charlotte, additional, Noone, Damien G., additional, Raghuram, Jyothi, additional, Shenoi, Susan, additional, Sivaraman, Vidya, additional, Tanner, Tamara, additional, Yeung, Rae S.M., additional, Cabral, David A., additional, and Morishita, Kimberly A., additional

Published
2021
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18. Assessing nephrology competence in general paediatrics—A survey of general paediatricians, paediatric nephrologists, residents, and program directors.

Author

Kirpalani, Amrit, Prasad, Charushree, Jawa, Natasha A, Atkinson, Adelle R, Feldman, Mark, Jeffers, Justin M, and Noone, Damien G

Subjects
KIDNEY disease treatments, CHRONIC kidney failure, HOSPITAL medical staff, CONFIDENCE intervals, KIDNEY stones, PEDIATRICS, EXECUTIVES, KIDNEY transplantation, SURVEYS, CONTINUING medical education, CLINICAL competence, SCALE analysis (Psychology), DESCRIPTIVE statistics, ACUTE kidney failure, CHILDREN
Abstract

Objective The objective of this study was to identify nephrology topics of lowest perceived competency and importance for general paediatricians. Methods Surveys were distributed to general paediatricians, paediatric residents, paediatric residency program directors, and paediatric nephrologists. Perceived importance and competence were rated on a 5-point Likert scale. Means and 95% confidence intervals were calculated. Results Mean perceived competency from general paediatricians across all nephrology domains was 3.0, 95%CI (2.9 to 3.1) and mean importance was 3.2, 95%CI (3.1 to 3.3). Domains scoring below the means for competence and importance, respectively were kidney stones (2.5, 95%CI [2.2 to 2.7]) and 2.6, 95%CI [2.3 to 2.8]), acute kidney injury (2.5, 95%CI [2.2 to 2.8] and 2.4, 95%CI [2.1 to 2.8]), chronic kidney disease (1.9, 95%CI [1.7 to 2.2] and 2.1, 95%CI [1.8 to 2.4]), tubular disorders (1.8, 95%CI [1.6 to 2.0] and 2.0, 95%CI [1.8 to 2.3]), and kidney transplant (1.6, 95%CI [1.4 to 1.8] and 1.7, 95%CI [1.4 to 1.9]). Residents, program directors, and paediatric nephrologists agreed that stones, chronic kidney disease, tubular disorders, and transplant were of lower importance. However, acute kidney injury was the domain with the largest discrepancy in perceived importance between residents (4.4, 95%CI [4.2 to 4.6]), nephrologists (4.2, 95%CI [3.8 to 4.6]), and program directors (4.2, 95%CI [3.7 to 4.7]) compared to general paediatricians ([2.4, 95%CI [2.1 to 2.8]; P<0.05). Conclusion Paediatricians did not believe acute kidney injury was important to their practice, despite expert opinion and evidence of long-term consequences. Educational interventions must address deficits in crucial domains of renal health in paediatrics. [ABSTRACT FROM AUTHOR]

Published
2022
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20. Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Author

Selewski, David T., primary, Ambruzs, Josephine M., additional, Appel, Gerald B., additional, Bomback, Andrew S., additional, Matar, Raed Bou, additional, Cai, Yi, additional, Cattran, Daniel C., additional, Chishti, Aftab S., additional, D'Agati, Vivette D., additional, D'Alessandri-Silva, Cynthia J., additional, Gbadegesin, Rasheed A., additional, Hogan, Jonathan J., additional, Iragorri, Sandra, additional, Jennette, J. Charles, additional, Julian, Bruce A., additional, Khalid, Myda, additional, Lafayette, Richard A., additional, Liapis, Helen, additional, Lugani, Francesca, additional, Mansfield, Sarah A., additional, Mason, Sherene, additional, Nachman, Patrick H., additional, Nast, Cynthia C., additional, Nester, Carla M., additional, Noone, Damien G., additional, Novak, Jan, additional, O'Shaughnessy, Michelle M., additional, Reich, Heather N., additional, Rheault, Michelle N., additional, Rizk, Dana V., additional, Saha, Manish K., additional, Sanghani, Neil S., additional, Sperati, C. John, additional, Sreedharan, Rajasree, additional, Srivastava, Tarak, additional, Swiatecka-Urban, Agnieszka, additional, Twombley, Katherine, additional, Vasylyeva, Tetyana L., additional, Weaver, Donald J., additional, Yin, Hong, additional, Zee, Jarcy, additional, Falk, Ronald J., additional, Gharavi, Ali G., additional, Gillespie, Brenda W., additional, Gipson, Debbie S., additional, Greenbaum, Larry A., additional, Holzman, Lawrence B., additional, Kretzler, Matthias, additional, Robinson, Bruce M., additional, Smoyer, William E., additional, Flessner, Michael, additional, Guay-Woodford, Lisa M., additional, Kiryluk, Krzysztof, additional, Gharavi, Ali, additional, Ahn, Wooin, additional, Avasare, Rupali S., additional, Babayev, Revekka, additional, Batal, Ibrahim, additional, Brown, Eric, additional, Campenot, Eric S., additional, Canetta, Pietro, additional, Chan, Brenda, additional, D’Agati, Vivette D., additional, Fernandez, Hilda, additional, Foroncewicz, Bartosz, additional, Ghiggeri, Gian Marco, additional, Hines, William H., additional, Jain, Namrata G., additional, Lin, Fangming, additional, Marasa, Maddalena, additional, Markowitz, Glen, additional, Mohan, Sumit, additional, Mucha, Krzysztof, additional, Nickolas, Thomas L., additional, Radhakrishnan, Jai, additional, Rao, Maya K., additional, Regunathan-Shenk, Renu, additional, Sanna-Cherchi, Simone, additional, Santoriello, Dominick, additional, Stokes, Michael B., additional, Yu, Natalie, additional, Valeri, Anthony M., additional, Zviti, Ronald, additional, Al-Uzri, Amira, additional, Ashoor, Isa, additional, Aviles, Diego, additional, Baracco, Rossana, additional, Barcia, John, additional, Bartosh, Sharon, additional, Belsha, Craig, additional, Braun, Michael C., additional, Chishti, Aftab, additional, Claes, Donna, additional, Cramer, Carl, additional, Davis, Keefe, additional, Erkan, Elif, additional, Feig, Daniel, additional, Freundlich, Michael, additional, Hanna, Melisha, additional, Hidalgo, Guillermo, additional, Jain, Amrish, additional, Kallash, Mahmoud, additional, Lane, Jerome C., additional, Mahan, John, additional, Mathews, Nisha, additional, Nester, Carla, additional, Pan, Cynthia, additional, Patel, Hiren, additional, Revell, Adelaide, additional, Steinke, Julia, additional, Wenderfer, Scott E., additional, Wong, Craig S., additional, Falk, Ronald, additional, Cook, William, additional, Derebail, Vimal, additional, Fogo, Agnes, additional, Gasim, Adil, additional, Gehr, Todd, additional, Harris, Raymond, additional, Kidd, Jason, additional, Laurin, Louis-Philippe, additional, Pendergraft, Will, additional, Pichette, Vincent, additional, Powell, Thomas Brian, additional, Renfrow, Matthew B., additional, Royal, Virginie, additional, Adler, Sharon, additional, Alpers, Charles, additional, Brown, Elizabeth, additional, Cattran, Daniel, additional, Choi, Michael, additional, Dell, Katherine M., additional, Dukkipati, Ram, additional, Fervenza, Fernando C., additional, Fornoni, Alessia, additional, Gadegbeku, Crystal, additional, Gipson, Patrick, additional, Hasely, Leah, additional, Hingorani, Sangeeta, additional, Hladunewich, Michelle A., additional, Hogan, Jonathan, additional, Jefferson, J. Ashley, additional, Jhaveri, Kenar, additional, Johnstone, Duncan B., additional, Kaskel, Frederick, additional, Kogan, Amy, additional, Kopp, Jeffrey, additional, Lemley, Kevin V., additional, Dieguez, Laura Malaga-, additional, Meyers, Kevin, additional, Neu, Alicia, additional, O’Shaughnessy, Michelle Marie, additional, O’Toole, John F., additional, Parekh, Rulan, additional, Reich, Heather, additional, Reidy, Kimberly, additional, Rondon, Helbert, additional, Sambandam, Kamalanathan K., additional, Sedor, John R., additional, Selewski, David T., additional, Sethna, Christine B., additional, Schelling, Jeffrey, additional, Swiatecka-Urban, Agnes, additional, Trachtman, Howard, additional, Tuttle, Katherine R., additional, Weisstuch, Joseph, additional, Zhdanova, Olga, additional, Gillespie, Brenda, additional, Barisoni, Laura, additional, Mansfield, Sarah, additional, Mariani, Laura, additional, and Wladkowski, Matthew, additional

Published
2018
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22. A curious case of growth failure and hypercalcemia: Answers

Author

Downie, Mallory L., primary, Mulder, Jaap, additional, Schneider, Rayfel, additional, Lim, Lillian, additional, Tehrani, Nasrin, additional, Wasserman, Jonathan D., additional, Fuchs, Shai, additional, John, Rohan, additional, Noone, Damien G., additional, and Hebert, Diane, additional

Published
2017
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23. A curious case of growth failure and hypercalcemia: Questions

Author

Downie, Mallory L., primary, Mulder, Jaap, additional, Schneider, Rayfel, additional, Lim, Lillian, additional, Tehrani, Nasrin, additional, Wasserman, Jonathan D., additional, Fuchs, Shai, additional, John, Rohan, additional, Noone, Damien G., additional, and Hebert, Diane, additional

Published
2017
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25. Genetic Determinants of Lupus Nephritis and Kidney Function in Systemic Lupus Erythematosus

Author

Khursigara, Magdalena Riedl, Gold, Nicholas, Dominguez, Daniela, Levy, Deborah, Noone, Damien G., Cao, Jingjing, Urowitz, Murray B., Onel, Karen S., Harvey, Elizabeth A., Lee, Chia-Chi J., Jefferies, Caroline, Wither, Joan, Kamen, Diane L., Pope, Janet, Peschken, Christine A., Petri, Michelle, Goldman, Daniel W., Tang, Thai-Son, Ishimori, Mariko, Knight, Andrea, Silverman, Earl, and Hiraki, Linda T.

Published
2023
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28. Hypertension in pediatric patients with chronic kidney disease: management challenges.

Author

Gallibois, Claire M., Jawa, Natasha A., and Noone, Damien G.

Subjects
HYPERTENSION, CHRONIC kidney failure in children, ALDOSTERONE, BLOOD pressure, HYPERKALEMIA
Abstract

In contrast to adults where hypertension is a leading cause of chronic kidney disease, in pediatrics, hypertension is predominantly a sequela, however, an important one that, like in adults, is likely associated with a more rapid decline in kidney function or progression of chronic kidney disease to end stage. There is a significant issue with unrecognized, or masked, hypertension in childhood chronic kidney disease. Recent evidence and, therefore, guidelines now suggest targeting a blood pressure of <50th percentile for age, sex, and height in children with proteinuria and chronic kidney disease. This often cannot be achieved by monotherapy and additional agents need to be added. Blockade of the renin angiotensin aldosterone system represents the mainstay of therapy, although often limited by the side effect of hyperkalemia. The addition of a diuretic, at least in the earlier stages of chronic kidney disease, might help mitigate this problem. [ABSTRACT FROM AUTHOR]

Published
2017
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31. Wide variation in glucocorticoid dosing in paediatric ANCA-associated vasculitis with renal disease: a paediatric vasculitis initiative study.

Author

Chen A, Mammen C, Guzman J, Al-Abadi E, Benseler SM, Berard RA, Gerstbacher D, Heshin-Bekenstein M, Kim S, Klein-Gitelman M, Chavan PP, James KE, Martin N, McErlane F, Myrup C, Noone DG, Raghuram J, Shenoi S, Sivaraman V, Tanner T, Yeung RSM, Cabral DA, and Morishita KA

Subjects
Adolescent, Adult, Antibodies, Antineutrophil Cytoplasmic, Child, Female, Glucocorticoids therapeutic use, Humans, Immunosuppressive Agents therapeutic use, Male, Remission Induction, Rituximab therapeutic use, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Microscopic Polyangiitis
Abstract

Objectives: High-dose glucocorticoids for remission-induction of ANCA-associated vasculitis are recommended and commonly used in adults, but recent studies suggest lower glucocorticoid doses can reduce toxicity without reducing efficacy. No paediatric-specific data exists to inform optimal glucocorticoid dosing in paediatric ANCA-associated vasculitis (pAAV). Our objectives were to describe glucocorticoid use in pAAV-related renal disease, and to explore associations between glucocorticoid dose, baseline patient characteristics and 12-month outcomes., Methods: Youth <18 years with pAAV, biopsy-confirmed pauci-immune glomerulonephritis and 12-month follow-up data were included from an international paediatric vasculitis registry. Presenting features and 12-month outcomes (eGFR, glucocorticoid-related adverse effects), were compared between patients receiving no, low-moderate (≤90mg/kg) and high (>90mg/kg) cumulative intravenous methylprednisolone (IVMP), and low (<0.5mg/kg/day prednisone equivalent), moderate (0.5-1.5mg/kg/day) and high (>1.5mg/kg/day) starting doses of oral glucocorticoids., Results: Among 131 patients (101 granulomatosis with polyangiitis, 30 microscopic polyangiitis), 27 (21%) received no IVMP, 64 (49%) low-moderate and 29 (22%) high-dose IVMP, while 9 (7%) received low, 75 (57%) moderate and 47 (36%) high initial doses of oral glucocorticoids. Renal failure at diagnosis (p=0.022) and plasmapheresis use (p=0.0001) were associated with high-dose IVMP. Rates of glucocorticoid-related adverse effects ranged from 15-31% across dose levels, and glucocorticoid dosing did not associate with 12-month outcomes., Conclusions: Glucocorticoid dosing for pAAV-related renal disease was highly variable, and rates of adverse effects were high across all dosing groups. A significant proportion of patients received oral glucocorticoid or IVMP doses that were discordant with current adult guidelines. Higher glucocorticoid doses did not associate with improved outcomes.

Published
2022
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32. Paediatric-to-adult transition experience in vasculitis: report of a model of care and outcomes.

Author

Mulla I, Yeung RSM, Noone DG, Bell-Peter A, and Pagnoux C

Subjects
Adolescent, Adult, Child, Humans, Recurrence, Retrospective Studies, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis drug therapy, Takayasu Arteritis drug therapy, Transition to Adult Care
Abstract

Objectives: Transitioning from paediatric to adult care can be challenging. Whereas transition models of care have been shared in some rheumatological conditions, reported experience in vasculitis is lacking., Methods: Retrospective chart review of adolescents aged 16-18 years assessed at the vasculitis transition clinic by paediatric and adult rheumatologists, and then scheduled for follow-up at the Adult Vasculitis Clinic (Toronto, Canada) from January 2013 until May 2020., Results: Twenty-eight patients were seen at the transition clinic and included. Mean age at transition was 17 years and 11 (± SD 2) months, with a mean follow up from diagnosis of 32 (± 24) months. Most patients had ANCA-associated vasculitis (N=19, 39%), followed by Takayasu's arteritis (N=4, 14%); all but one were in remission at the time of transition. Twenty-six (93%) patients showed up for their first booked adult visit (two did not, were called and rebooked), after a mean of 4 (± 2) months after transition clinic. Subsequently, two patients missed 1 appointment, and three missed ≥ 2 appointments; only one (4%) stopped coming, while in remission for >2 years post-transition. Five (18%) patients were identified to have medication non-adherence after transition. With a mean follow up post-transition of 32 (± 25) months, 7 (25%) patients had minor and five (18%) had major relapses, at a mean of 17 (± 9) and 25 (± 15) months post-transition, respectively (compared to 12 (43%) and 9 (32%) prior to transition). At their last visit, all were in remission, 18 (64%) off glucocorticoids, and damage had remained stable., Conclusions: This model of care of vasculitis transition clinic resulted in favourable outcomes, as reflected by continuity of follow-up, and no increased risk of relapse.

Published
2022
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