Rationale and design of the Nephrotic Syndrome Study Network (NEPTUNE) Match in glomerular diseases: designing the right trial for the right patient, today

Trachtman, Howard; Desmond, Hailey; Williams, Amanda L.; Mariani, Laura H.; Eddy, Sean; Ju, Wenjun; Barisoni, Laura; Ascani, Heather K.; Uhlmann, Wendy R.; Spino, Cathie; Holzman, Lawrence B.; Sedor, John R.; Gadegbeku, Crystal; Subramanian, Lalita; Lienczewski, Chrysta C.; Manieri, Tina; Roberts, Scott J.; Gipson, Debbie S.; Kretzler, Matthias; Massengill, Susan; Lo, Layla; Dell, Katherine; O’Toole, John; Sedor, John; Martin, Blair; Macumber, Ian; Sharma, Silpa; Srivastava, Tarak; Markus, Kelsey; Sethna, Christine; Vento, Suzanne; Canetta, Pietro; Olabisi, Opeyemi; Gbadegesin, Rasheed; Smith, Maurice; Greenbaum, Laurence; Wang, Chia-shi; Yun, Emily; Adler, Sharon; LaPage, Janine; Amarah, Amatur; Itteera, Mathew; Atkinson, Meredith; Williams, Miahje; Lieske, John; Hogan, Marie; Fervenza, Fernando; Selewski, David; Alston, Cheryl; Reidy, Kim; Ross, Michael; Kaskel, Frederick; Flynn, Patricia; Malaga-Dieguez, Laura; Zhdanova, Olga; Pehrson, Laura Jane; Miranda, Melanie; Almaani, Salem; Roberts, Laci; Lafayette, Richard; Dave, Shiktij; Lee, Iris; Shah, Shweta; Batla, Sadaf; Reich, Heather; Hladunewich, Michelle; Ling, Paul; Romano, Martin; Brakeman, Paul; Dylewski, James; Rogers, Nathan; McCarthy, Ellen; Creed, Catherine; Fornoni, Alessia; Bandes, Miguel; Kretzler, Matthias; Mariani, Laura; Modi, Zubin; Williams, A.; Ni, Roxy; Nachman, Patrick; Rheault, Michelle; Kowalski, Amy; Rauwolf, Nicolas; Derebail, Vimal; Gibson, Keisha; Froment, Anne; Kelley, Sara; Holzman, Lawrence; Meyers, Kevin; Kallem, Krishna; Edwards, Aliya; Sharma, Samin; Roehm, Elizabeth; Sambandam, Kamalanathan; Brown, Elizabeth; Hellewege, Jamie; Jefferson, Ashley; Hingorani, Sangeeta; Tuttle, Katherine; Manahan, Linda; Pao, Emily; Kuykendall, Kelli; Lin, Jen Jar; Dharnidharka, Vikas; Kretzler, Matthias; Gillespie, Brenda; Mariani, Laura; Modi, Zubin; Salmon, Eloise; Trachtman, Howard; Mainieri, Tina; Alter, Gabrielle; Arbit, Michael; Desmond, Hailey; Eddy, Sean; Fermin, Damian; Ju, Wenjun; Larkina, Maria; Lienczewski, Chrysta; Scherr, Rebecca; Troost, Jonathan; Williams, Amanda; Zhai, Yan; Kincaid, Colleen; Li, Shengqian; Li, Shannon; Gadegbeku, Crystal; Barisoni, Laura; Sedor, John; Sampson, Matthew G.; Smith, Abigail; Holzman, Lawrence; Zee, Jarcy; Avila-Casado, Carmen; Bagnasco, Serena; Bu, Lihong; Caltharp, Shelley; Cassol, Clarissa; Demeke, Dawit; Gillespie, Brenda; Hassler, Jared; Herlitz, Leal; Hewitt, Stephen; Hodgin, Jeff; Holanda, Danni; Kambham, Neeraja; Lemley, Kevin; Mariani, Laura; Messias, Nidia; Mikhailov, Alexei; Moreno, Vanessa; Najafian, Behzad; Palmer, Matthew; Rosenberg, Avi; Royal, Virginie; Sekulik, Miroslav; Stokes, Barry; Thomas, David; Wu, Ming; Yamashita, Michifumi; Yin, Hong; Zee, Jarcy; Zuo . Cochairs, Yiqin; Barisoni, Laura; Nast, Cynthia

doi:10.1016/j.kint.2023.11.018

Cited by 5 publications

(2 citation statements)

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“…Importantly, it has yet to be systematically demonstrated that the availability of spatial transcriptomic profiling data can positively impact clinical decision making, though anecdotes of such are emerging from KPMP studies [35,72]. A new initiative termed NEPTUNE Match integrates clinical, biomarker, and laboratory data (including several -omics technologies) to identify glomerular disease pathways that may be active in individual patients [73]. This information is then used to guide these individuals toward clinical trials that may be best positioned to address their underlying glomerular disease mechanism.…”

Section: Insights Into Kidney Disease Gleaned From Spatial Transcript...mentioning

confidence: 99%

Challenges and Opportunities for the Clinical Translation of Spatial Transcriptomics Technologies

Smith,

Prince,

MacDonald

et al. 2024

Glomerular Dis

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Background: The first spatially resolved transcriptomics platforms, GeoMx (Nanostring) and Visium (10x Genomics) were launched in 2019 and were recognized as the method of the year by Nature Methods in 2020. The subsequent refinement and expansion of these and other technologies to increase -plex, work with formalin-fixed paraffin-embedded tissue, and analyze protein in addition to gene expression have only added to their significance and impact on the biomedical sciences. In this perspective, we focus on two platforms for spatial transcriptomics, GeoMx and Visium, and how these platforms have been used to provide novel insight into kidney disease. The choice of platform will depend largely on experimental questions and design. The application of these technologies to clinically sourced biopsies presents the opportunity to identify specific tissue biomarkers that help define disease etiology and more precisely target therapeutic interventions in the future. Summary: In this review, we provide a description of the existing and emerging technologies that can be used to capture spatially resolved gene and protein expression data from tissue. These technologies have provided new insight into the spatial heterogeneity of diseases, how reactions to disease are distributed within a tissue, which cells are affected, and molecular pathways that predict disease and response to therapy. Key Message: The upcoming years will see intense use of spatial transcriptomics technologies to better define the pathophysiology of kidney diseases and develop novel diagnostic tests to guide personalized treatments for patients.

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Section: Insights Into Kidney Disease Gleaned From Spatial Transcript...mentioning

confidence: 99%

Challenges and Opportunities for the Clinical Translation of Spatial Transcriptomics Technologies

Smith,

Prince,

MacDonald

et al. 2024

Glomerular Dis

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“…Patients with their biomarker profiles are subsequently matched with molecular targeted therapies to align the right therapy to the right patient. 7 The NEPTUNE-Match platform allows for optimal contribution of the patients with rare disease to the best matching clinical trials. A critical prerequisite is the availability of a trial network recruiting a broad patient population willing to participate in the trial-match process.…”

Section: Randomized Biomarker-stratified Designsmentioning

confidence: 99%

Clinical Trials for Kidney Disease in the Era of Personalized Medicine

Heerspink,

Kretzler

2024

JASN

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Several new effective therapies have emerged in the last 5 years for patients with CKD, including sodium-glucose cotransporter 2 inhibitors and the mineralocorticoid receptor antagonist finerenone. Furthermore, many new therapeutic strategies and interventions are in advanced stages of development to further reduce CKD progression. These new therapies were tested in dedicated randomized controlled trials (RCTs), which provide high-level evidence about the efficacy and safety of existing or novel interventions for the population at large. However, these RCTs did not take into account variability in underlying disease mechanism and response among individuals. However, advancements in the application of high-throughput data-intensive analytical and bioinformatic technologies have revealed a large variation in disease pathophysiology, molecular pathways involved in disease progression, and response to treatment. This is illustrated by a recent kidneytranscriptomic biopsy study demonstrating a large heterogeneity in tissue morphological features and molecular signatures that could not be captured with the current classification system for CKD. 1 Because of the substantial heterogeneity in underlying disease pathophysiology and response to treatment, clinical trials recruit a large number of patients and consequently have become complex and increasingly challenging to manage. With the advent of multiple new effective therapies, the average CKD progression rate is decreasing, which will likely lead to even larger trials to maintain sufficient statistical power. Indeed, the aim of a recently announced clinical trial in nephrology was to recruit 11,000 patients. 2 This appears to be unsustainable for the future.New clinical trial designs should therefore be considered that take into account the variation in therapy response according the concept of personalized medicine. This has the potential of smaller and more efficient clinical trials and better patient outcomes. Some early studies in the nephrology area have explored innovative clinical trial designs and have provided important insights to apply personalized medicine approaches in future clinical trials.

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Urinary Biomarkers: Toward a Liquid Biopsy for Lupus Nephritis

Fava

2024

Arthritis & Rheumatology

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Rationale and design of the Nephrotic Syndrome Study Network (NEPTUNE) Match in glomerular diseases: designing the right trial for the right patient, today

Cited by 5 publications

References 34 publications

Challenges and Opportunities for the Clinical Translation of Spatial Transcriptomics Technologies

Challenges and Opportunities for the Clinical Translation of Spatial Transcriptomics Technologies

Clinical Trials for Kidney Disease in the Era of Personalized Medicine

Urinary Biomarkers: Toward a Liquid Biopsy for Lupus Nephritis

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