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Article ; Online: Corrigendum to Novel Treatment Paradigms: Focal Segmental Glomerulosclerosis Kidney International Reports, Volume 8, Issue 1, January 2023, Pages 30-35.

de Cos, Marina / Meliambro, Kristin / Campbell, Kirk N

Kidney international reports

2023 Volume 8, Issue 4, Page(s) 949

Abstract: This corrects the article DOI: 10.1016/j.ekir.2022.10.004.]. ...

Abstract	[This corrects the article DOI: 10.1016/j.ekir.2022.10.004.].
Language	English
Publishing date	2023-01-25
Publishing country	United States
Document type	Published Erratum
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2023.01.026
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Article ; Online: Novel Treatment Paradigms: Focal Segmental Glomerulosclerosis.

de Cos, Marina / Meliambro, Kristin / Campbell, Kirk N

Kidney international reports

2022 Volume 8, Issue 1, Page(s) 30–35

Abstract: Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of injury defined by the presence of sclerosis in some (segmental) of certain glomeruli (focal). On electron microscopy, it is characterized by a variable degree of podocyte foot process ... ...

Abstract	Focal segmental glomerulosclerosis (FSGS) is a histologic pattern of injury defined by the presence of sclerosis in some (segmental) of certain glomeruli (focal). On electron microscopy, it is characterized by a variable degree of podocyte foot process effacement and gaps in the coverage of the glomerular basement membrane. The pattern of injury occurs when podocytes, highly differentiated cells with limited regenerative capacity, are reduced in number. The heterogeneity in underlying causes of podocyte loss results in equally variable clinical phenotypes. Recent work acknowledging advances in defining the genetic and immunologic basis of disease has redefined the classification of FSGS. Unprecedented clinical trial activity and efficacy of repurposed agents presents hope for improved therapeutic options. This minireview summarizes recent advances with a focus on novel treatment paradigms in FSGS.
Language	English
Publishing date	2022-10-08
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2022.10.004
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Article ; Online: Hippo pathway deficiency and recovery from heart failure after myocardial infarction: potential implications for kidney disease.

Meliambro, Kristin / Campbell, Kirk N

Kidney international

2018 Volume 93, Issue 2, Page(s) 290–292

MeSH term(s)	Heart Failure ; Heart Failure, Systolic ; Humans ; Infarction ; Kidney Diseases ; Myocardial Infarction ; Protein-Serine-Threonine Kinases
Chemical Substances	Hippo protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2018-02-01
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2017.12.001
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Zs.A 797: Show issues

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Article ; Online: Therapy for Proliferative Lupus Nephritis.

Meliambro, Kristin / Campbell, Kirk N / Chung, Miriam

Rheumatic diseases clinics of North America

2018 Volume 44, Issue 4, Page(s) 545–560

Abstract: Proliferative lupus nephritis requires prompt diagnosis and treatment with immunosuppressive therapy. Cyclophosphamide is the longest studied agent, but mycophenolate mofetil has recently emerged as an efficacious induction and maintenance treatment that ...

Abstract	Proliferative lupus nephritis requires prompt diagnosis and treatment with immunosuppressive therapy. Cyclophosphamide is the longest studied agent, but mycophenolate mofetil has recently emerged as an efficacious induction and maintenance treatment that does not impart the risk of infertility. However, overall remission rates remain suboptimal and there is a need for improved therapeutic options. To this end, ongoing clinical studies are focusing on agents that target key molecules and pathways implicated in the pathogenesis of lupus nephritis based on previous animal and human studies. This article reviews key findings of trials supporting established induction and maintenance treatment regimens along with novel therapeutic investigations.
MeSH term(s)	Humans ; Immunosuppressive Agents/classification ; Immunosuppressive Agents/pharmacology ; Lupus Nephritis/diagnosis ; Lupus Nephritis/immunology ; Lupus Nephritis/therapy ; Maintenance Chemotherapy/methods ; Remission Induction/methods ; Therapies, Investigational
Chemical Substances	Immunosuppressive Agents
Language	English
Publishing date	2018-09-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	92118-x
ISSN	1558-3163 ; 0889-857X
ISSN (online)	1558-3163
ISSN	0889-857X
DOI	10.1016/j.rdc.2018.06.002
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Article ; Online: Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis.

Moledina, Dennis G / Obeid, Wassim / Smith, Rex N / Rosales, Ivy / Sise, Meghan E / Moeckel, Gilbert / Kashgarian, Michael / Kuperman, Michael / Campbell, Kirk N / Lefferts, Sean / Meliambro, Kristin / Bitzer, Markus / Perazella, Mark A / Luciano, Randy L / Pober, Jordan S / Cantley, Lloyd G / Colvin, Robert B / Wilson, F Perry / Parikh, Chirag R

The Journal of clinical investigation

2024 Volume 134, Issue 6

MeSH term(s)	Humans ; Nephritis, Interstitial/diagnosis ; Biomarkers ; Acute Disease ; Chemokine CXCL9
Chemical Substances	Biomarkers ; CXCL9 protein, human ; Chemokine CXCL9
Language	English
Publishing date	2024-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI180583
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Ua VI Zs.184: Show issues

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Article ; Online: Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis.

Kidney international reports

2024 Volume 9, Issue 5, Page(s) 1354–1368

Abstract: Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease leading to end-stage kidney disease (ESKD), is characterized by podocyte injury and depletion, whereas minimal change disease (MCD) has better outcomes ... ...

Abstract	Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease leading to end-stage kidney disease (ESKD), is characterized by podocyte injury and depletion, whereas minimal change disease (MCD) has better outcomes despite podocyte injury. Identifying mechanisms capable of preventing podocytopenia during injury could transform FSGS to an "MCD-like" state. Preclinical data have reported conversion of an MCD-like injury to one with podocytopenia and FSGS by inhibition of AMP-kinase (AMPK) in podocytes. Conversely, in FSGS, AMPK-activation using metformin (MF) mitigated podocytopenia and azotemia. Observational studies also support beneficial effects of MF on proteinuria and chronic kidney disease (CKD) outcomes in diabetes. A randomized controlled trial (RCT) to test MF in podocyte injury with FSGS has not yet been conducted. Methods: We report the rationale and design of phase 2, double-blind, placebo-controlled RCT evaluating the efficacy and safety of MF as adjunctive therapy in FSGS. By randomizing 30 patients with biopsy-confirmed FSGS to MF or placebo (along with standard immunosuppression), we will study mechanistic biomarkers that correlate with podocyte injury or depletion and evaluate outcomes after 6 months. We specifically integrate novel urine, blood, and tissue markers as surrogates for FSGS progression along with unbiased profiling strategies. Results and conclusion: Our phase 2 trial will provide insight into the potential efficacy and safety of MF as adjunctive therapy in FSGS-a crucial step to developing a larger phase 3 study. The mechanistic assays here will guide the design of other FSGS trials and contribute to understanding AMPK activation as a potential therapeutic target in FSGS. By repurposing an inexpensive agent, our results will have implications for FSGS treatment in resource-poor settings.
Language	English
Publishing date	2024-02-13
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2024.02.006
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Article ; Online: Urinary Plasminogen as a Marker of Disease Progression in Human Glomerular Disease.

American journal of kidney diseases : the official journal of the National Kidney Foundation

2024

Abstract: Rationale & objective: Glomerular disorders have a highly variable clinical course, and biomarkers that reflect the molecular mechanisms underlying their progression are needed. Based on our previous work identifying plasminogen as a direct cause of ... ...

Abstract	Rationale & objective: Glomerular disorders have a highly variable clinical course, and biomarkers that reflect the molecular mechanisms underlying their progression are needed. Based on our previous work identifying plasminogen as a direct cause of podocyte injury, we designed this study to test the association between urine plasmin(ogen) (ie, plasmin and its precursor plasminogen) and end-stage kidney disease (ESKD). Study design: Multicenter cohort study. Setting & participants: 1,010 patients enrolled in the CureGN Cohort with biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A nephropathy). Predictors: The main predictor was urine plasmin(ogen) at baseline. Levels were measured by an electrochemiluminescent immunoassay developed de novo. Traditional clinical and analytical characteristics were used for adjustment. The ratio of urine plasmin(ogen)/expected plasmin(ogen) was evaluated as a predictor in a separate model. Outcome: Progression to ESKD. Analytical approach: Cox regression was used to examine the association between urinary plasmin(ogen) and time to ESKD. Urinary markers were log Results: Adjusted Log Limitations: Single plasmin(ogen) determination does not allow for the study of changes over time. The use of a cohort of mostly white patients and the restriction to patients with 3 glomerular disorders limits the external validity of our analysis. Conclusions: Urinary plasmin(ogen) and the ratio of measured/expected plasmin(ogen) are independently associated with ESKD in a cohort of patients with glomerular disease. Taken together with our previous experimental findings, urinary plasmin(ogen) could be a useful biomarker in prognostic decision making and a target for the development of novel therapies in patients with proteinuria and glomerular disease. Plain-language summary: Glomerular diseases are an important cause of morbidity and mortality in patients of all ages. Knowing the individual risk of progression to dialysis or transplantation would help to plan the follow-up and treatment of these patients. Our work studies the usefulness of urinary plasminogen as a marker of progression in this context, since previous studies indicate that plasminogen may be involved in the mechanisms responsible for the progression of these disorders. Our work in a sample of 1,010 patients with glomerular disease demonstrates that urinary plasminogen (as well as the ratio of measured to expected plasminogen) is associated with the risk of progression to end-stage kidney disease. Urine plasminogen exhibited good performance and, if further validated, could enable risk stratification for timely interventions in patients with proteinuria and glomerular disease.
Language	English
Publishing date	2024-03-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2024.01.520
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Zs.A 1669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 468: Show issues

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Article ; Online: KIBRA upregulation increases susceptibility to podocyte injury and glomerular disease progression.

Meliambro, Kristin / Yang, Yanfeng / de Cos, Marina / Rodriguez Ballestas, Estefania / Malkin, Caroline / Haydak, Jonathan / Lee, John R / Salem, Fadi / Mariani, Laura H / Gordon, Ronald E / Basgen, John M / Wen, Huei Hsun / Fu, Jia / Azeloglu, Evren U / He, John Cijiang / Wong, Jenny S / Campbell, Kirk N

JCI insight

2023 Volume 8, Issue 7

Abstract: Despite recent progress in the identification of mediators of podocyte injury, mechanisms underlying podocyte loss remain poorly understood, and cell-specific therapy is lacking. We previously reported that kidney and brain expressed protein (KIBRA), ... ...

Abstract	Despite recent progress in the identification of mediators of podocyte injury, mechanisms underlying podocyte loss remain poorly understood, and cell-specific therapy is lacking. We previously reported that kidney and brain expressed protein (KIBRA), encoded by WWC1, promotes podocyte injury in vitro through activation of the Hippo signaling pathway. KIBRA expression is increased in the glomeruli of patients with focal segmental glomerulosclerosis, and KIBRA depletion in vivo is protective against acute podocyte injury. Here, we tested the consequences of transgenic podocyte-specific WWC1 expression in immortalized human podocytes and in mice, and we explored the association between glomerular WWC1 expression and glomerular disease progression. We found that KIBRA overexpression in immortalized human podocytes promoted cytoplasmic localization of Yes-associated protein (YAP), induced actin cytoskeletal reorganization, and altered focal adhesion expression and morphology. WWC1-transgenic (KIBRA-overexpressing) mice were more susceptible to acute and chronic glomerular injury, with evidence of YAP inhibition in vivo. Of clinical relevance, glomerular WWC1 expression negatively correlated with renal survival among patients with primary glomerular diseases. These findings highlight the importance of KIBRA/YAP signaling to the regulation of podocyte structural integrity and identify KIBRA-mediated injury as a potential target for podocyte-specific therapy in glomerular disease.
MeSH term(s)	Humans ; Mice ; Animals ; Podocytes/metabolism ; Up-Regulation ; Kidney Glomerulus/metabolism ; Signal Transduction ; Kidney Diseases/genetics ; Kidney Diseases/metabolism ; Disease Progression ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism
Chemical Substances	WWC1 protein, human ; Intracellular Signaling Peptides and Proteins
Language	English
Publishing date	2023-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.165002
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Article ; Online: Repository Corticotropin Injections Promote Clinical Remission and Regulatory T Cell Expansion in Membranous Nephropathy.

Hartzell, Susan / Sanchez-Russo, Luis / Pecchio, Isabella Perez / Okoroafor, Ibeawuchi / Meliambro, Kristin / Bin, Sofia / Fribourg, Miguel / Cantarelli, Chiara / Campbell, Kirk N / Cravedi, Paolo

Kidney international reports

2021 Volume 6, Issue 9, Page(s) 2491–2495

Language	English
Publishing date	2021-06-22
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2021.06.010
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Article ; Online: Association of Vaccination with the Persistence of Post-COVID Symptoms.

Wisnivesky, Juan P / Govindarajulu, Usha / Bagiella, Emilia / Goswami, Ruchir / Kale, Minal / Campbell, Kirk N / Meliambro, Kristin / Chen, Zijian / Aberg, Judith A / Lin, Jenny J

Journal of general internal medicine

2022 Volume 37, Issue 7, Page(s) 1748–1753

Abstract: Background: Patients who have had COVID-19 often report persistent symptoms after resolution of their acute illness. Recent reports suggest that vaccination may be associated with improvement in post-acute symptoms. We used data from a prospective ... ...

Abstract	Background: Patients who have had COVID-19 often report persistent symptoms after resolution of their acute illness. Recent reports suggest that vaccination may be associated with improvement in post-acute symptoms. We used data from a prospective cohort to assess differences in post-acute sequelae of COVID (PASC) among vaccinated vs. unvaccinated patients. Methods: We used data from a cohort of COVID-19 patients enrolled into a prospective registry established at a tertiary care health system in New York City. Participants underwent a baseline evaluation before COVID-19 vaccines were available and were followed 6 months later. We compared unadjusted and propensity score-adjusted baseline to 6-month change for several PASC-related symptoms and measures: anosmia, respiratory (cough, dyspnea, phlegm, wheezing), depression, anxiety, post-traumatic stress disorder (PTSD; COVID-19-related and other trauma), and quality-of-life domains among participants who received vs. those who did not receive COVID-19 vaccination. Results: The study included 453 COVID-19 patients with PASC, of which 324 (72%) were vaccinated between the baseline and 6-month visit. Unadjusted analyses did not show significant differences in the baseline to 6-month change in anosmia, respiratory symptoms, depression, anxiety, PTSD, or quality of life (p > 0.05 for all comparisons) among vaccinated vs. unvaccinated patients. Similar results were found in propensity-adjusted comparisons and in secondary analyses based on the number of vaccine doses received. Conclusions: Our findings suggest that COVID vaccination is not associated with improvement in PASC. Additional studies are needed to better understand the mechanisms underlying PASC and to develop effective treatments.
MeSH term(s)	Anosmia ; COVID-19/epidemiology ; COVID-19/prevention & control ; COVID-19 Vaccines ; Disease Progression ; Humans ; Quality of Life ; SARS-CoV-2 ; Vaccination
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2022-03-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	639008-0
ISSN	1525-1497 ; 0884-8734
ISSN (online)	1525-1497
ISSN	0884-8734
DOI	10.1007/s11606-022-07465-w
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