{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:51:00Z","timestamp":1792788660406,"version":"4.5.0"},"reference-count":21,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/R013942\/1"],"award-info":[{"award-number":["MR\/R013942\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["097820"],"award-info":[{"award-number":["097820"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202860"],"award-info":[{"award-number":["202860"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Manchester Academic Healthcare Science Centre","award":["186\/200"],"award-info":[{"award-number":["186\/200"]}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>Background Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are patterns of kidney injury observed in the filtering units of the kidney known as glomeruli. These histological patterns are seen in kidney biopsies from individuals with idiopathic nephrotic syndrome (iNS), which occurs in both children and adults. However, there is some indication that MCD and FSGS are within the same phenotypic spectrum. Methods From the NURTuRE cohort of individuals with NS, we performed laser microdissection and mass spectrometry analysis of kidney biopsy samples to identify proteomic patterns of disease. 56 individuals with iNS segregated by histological pattern (37 MCD and 19 FSGS) across three age groups: early childhood (0\u20136 years), late childhood (6\u201318 years) and adult (&gt;18 years). Results We found no distinct clustering of proteomic profiles between MCD and FSGS, but identified global differences in glomerular cell and extracellular matrix composition related to both histological pattern and age. The proteomic data are available via ProteomeXchange with identifier PXD053362. Conclusions The lack of distinct clustering between MCD and FSGS in our study suggests shared biological processes between these injury patterns of iNS, supporting the hypothesis that they are part of the same disease spectrum. The global differences observed in glomerular cell and extracellular matrix composition suggest involvement of diverse biogeological processes as different patterns of iNS manifests in different age groups. This study also demonstrates the feasibility of pooling bioresources, central processing of heterogeneous tissue samples, and developing laser-microdissection and proteomic analysis methodology.<\/ns3:p>","DOI":"10.12688\/wellcomeopenres.22633.1","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T07:45:09Z","timestamp":1735026309000},"page":"731","update-policy":"https:\/\/doi.org\/10.12688\/wellcomeopenres.crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Proteomic profiling of kidney biopsies in nephrotic 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Unified Renal Translational Research Enterprise: Idiopathic Nephrotic Syndrome (NURTuRE-INS) study.","volume":"17","author":"E Colby","year":"2024","journal-title":"Clin Kidney J."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"1185-1189","DOI":"10.1136\/bmj.39576.709711.80","article-title":"Nephrotic syndrome in adults.","volume":"336","author":"R Hull","year":"2008","journal-title":"BMJ."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"629-639","DOI":"10.1016\/S0140-6736(03)14184-0","article-title":"Nephrotic syndrome in childhood.","volume":"362","author":"A Eddy","year":"2003","journal-title":"Lancet."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"S1-S276","DOI":"10.1016\/j.kint.2021.05.021","article-title":"KDIGO 2021 clinical practice guideline for the management of glomerular diseases","volume":"100","year":"2021","journal-title":"Kidney Int."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"768-776","DOI":"10.1038\/nrneph.2016.147","article-title":"Minimal Change Disease and idiopathic FSGS: manifestations of the same disease.","volume":"12","author":"R Maas","year":"2016","journal-title":"Nat Rev Nephrol."},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"422-433","DOI":"10.1056\/NEJMoa2314471","article-title":"Autoantibodies targeting nephrin in podocytopathies.","volume":"391","author":"F Hengel","year":"2024","journal-title":"N Engl J Med."},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"238-252","DOI":"10.1681\/ASN.2021060794","article-title":"Discovery of autoantibodies targeting nephrin in Minimal Change Disease supports a novel autoimmune etiology.","volume":"33","author":"A Watts","year":"2022","journal-title":"J Am Soc Nephrol."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"750-765","DOI":"10.1038\/s41581-019-0217-5","article-title":"Molecular stratification of Idiopathic Nephrotic Syndrome.","volume":"15","author":"M Saleem","year":"2019","journal-title":"Nat Rev Nephrol."},{"key":"ref-11","doi-asserted-by":"publisher","first-page":"807-819.e1","DOI":"10.1053\/j.ajkd.2021.10.004","article-title":"Quantification of glomerular structural lesions: associations with clinical outcomes and transcriptomic profiles in nephrotic syndrome.","volume":"79","author":"J Hodgin","year":"2022","journal-title":"Am J Kidney Dis."},{"key":"ref-12","doi-asserted-by":"publisher","first-page":"2705-2724","DOI":"10.1681\/ASN.2020030286","article-title":"Extracellular Matrix injury of kidney allografts in antibody-mediated rejection: a proteomics study.","volume":"31","author":"S Clotet-Freixas","year":"2020","journal-title":"J Am Soc Nephrol."},{"key":"ref-13","doi-asserted-by":"publisher","first-page":"2301-2319","DOI":"10.1038\/nprot.2016.136","article-title":"The MaxQuant computational platform for Mass Spectrometry-based shotgun 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Spectrometry shotgun proteomic analysis.","volume":"8","author":"R Sprung","year":"2009","journal-title":"Mol Cell Proteomics."},{"key":"ref-21","article-title":"Proteomic profiling of kidney biopsies in nephrotic syndrome"}],"container-title":["Wellcome Open 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status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.21956\/wellcomeopenres.24934.r116551, Andrea Angeletti, Dialysis and Transplantation Unit, IRCCS Istituto Giannina Gaslini, Genoa, 13 Jan 2025, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-731\/v1#referee-response-116551","order":0,"name":"referee-response-116551","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Anna Shanshan Li<\/b>; \n<i>Posted: 03 Feb 2025<\/i>; We thank the reviewer for their positive evaluation of our manuscript and insightful comments. We especially appreciate the recognition of our innovative methodology and the translational potential of this work, which highlights the impact our approach can have on the field of nephrology. We acknowledge the potential for sample heterogeneity introduced by variations in collection and processing across the different centres. This is an inherent challenge when working with a valuable resource like the NURTURE biorepository. While we could not retrospectively control for these variations, we have transparently identified this as a limitation and advocate for the implementation of standardised protocols in future studies. We also agree that the small sample size, especially in certain subgroups, might limit the broader applicability of our findings. Nonetheless, we believe our study serves as an important proof-of-concept, demonstrating the feasibility and value of applying proteomic analysis to kidney biopsies. These findings pave the way for larger, multi-centre studies with greater statistical power. Due to these limitations, we have been cautious about drawing extensive conclusions or delving too deeply into clinical relevance and negative results. However, we believe this study provides a valuable foundation for future research in this area and are excited about the potential of proteomics to improve our understanding and treatment of nephrotic syndrome. The establishment of a new study with standardised protocols will undoubtedly help overcome the current limitations and contribute to a deeper understanding of the molecular mechanisms underlying nephrotic syndrome.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-731\/v1#referee-comment-6021","order":1,"name":"referee-comment-6021","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.24934.r116557, Manoj Anant Dhanorkar, Nephrology, All India Institute of Medical Sciences, Nagpur, Nagpur, Maharashtra, 13 Jan 2025, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-731\/v1#referee-response-116557","order":2,"name":"referee-response-116557","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Anna Shanshan Li<\/b>; \n<i>Posted: 03 Feb 2025<\/i>; Thank you for taking time to review our manuscript. We have the following responses to the points you have raised. \n<b>Limitation of the study<\/b> Sample Selection: We acknowledge that the information available for sample selection from the NURTuRE repository was limited.&nbsp; However, this limitation is inherent in utilising a pre-existing biorepository.&nbsp; We have stated this limitation in the Discussion section of our manuscript.&nbsp; &nbsp; Clinical Data: Our focus for this paper is to report the proteomic profiles of these biopsies, which provide valuable insights into the molecular landscape of MCD and FSGS. We acknowledge that further details regarding the patients and their clinical course would be valuable. However, as mentioned in the manuscript, the clinical information available in the NURTuRE repository was limited. We have also highlighted this limitation in the Discussion section.&nbsp; &nbsp; \n<b>MCD and FSGS in nephrotic syndrome<\/b> Our findings support the hypothesis that MCD and FSGS may represent different manifestations of the same pathology spectrum.&nbsp; However, this does not necessarily imply that MCD is an earlier stage that inevitably progresses to FSGS.&nbsp; &nbsp; Steroid Resistance: As discussed in our manuscript, there is a difference in the timing of biopsies between children and adults, with children typically undergoing a trial of steroid treatment before a biopsy is considered, while adults tend to be biopsied at the time of disease presentation.&nbsp; It is important to note that steroid resistance is not a reliable distinguishing factor between MCD and FSGS, and this has already been reported in the literature. \n<b>Tissue Proteomics vs. Urine Proteomics:<\/b> It is important to emphasise that tissue proteomics and urine proteomics provide distinct information.&nbsp; Tissue proteomics reflects the protein composition within an organ itself, while urine proteomics captures proteins from multiple tissue origins.&nbsp; Therefore, it is not surprising that our findings may differ from previous studies that have focused on urine proteomics.&nbsp; &nbsp; \n<b>Conclusion:<\/b> We believe that our conclusions are adequately supported by the results of our study.&nbsp; We have identified both significant overlaps and differences in protein expression between MCD and FSGS across different age groups.&nbsp; These findings provide new insights into the molecular landscape of these histological patterns of nephrotic syndrome.","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-731\/v1#referee-comment-6022","order":3,"name":"referee-comment-6022","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.24934.r118273, Robert W Hunter, Royal Infirmary of Edinburgh, Queen\u2019s Medical Research Institute, Edinburgh, 21 Feb 2025, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-731\/v1#referee-response-118273","order":4,"name":"referee-response-118273","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.24934.r116554, Federica Collino, University of Milano, Clinical Sciences and Community Health, Milan, 25 Feb 2025, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/9-731\/v1#referee-response-116554","order":5,"name":"referee-response-116554","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by Wellcome [097820, an Institutional Strategic Support Fund (ISSF) award to the University of Manchester]. RL was supported by a Wellcome Senior Research Fellowship (202860). The NURTuRE Biobank was funded by an MRC Research Grant (MR\/R013942\/1). Funding for the NURTuRE biobank was provided by commercial partners to Kidney Research UK: UCB Biopharma, Evotec International GmbH, AstraZeneca, AbbVie and Travere Therapeutics. Funding was provided through a formal collaboration agreement and awarded to the academic investigators as a research grant after peer review.  Further funding for this project was obtain by an MRC Precision Medicine grant (MR\/R013942\/1) to MS. We also acknowledge support from the Manchester Academic Healthcare Science Centre (MAHSC) (186\/200). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":6,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}