{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T21:59:24Z","timestamp":1788472764229,"version":"build-2803163510"},"reference-count":36,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Diabetic nephropathy (DN) is one of the key causes of end-stage kidney disease worldwide, especially in developed countries. The classic pathogenic development of DN is characterized by microalbuminuria which would progress to nephrotic-range proteinuria and loss of kidney function. The degree of albuminuria is considered an independent risk factor for all-cause mortality in patients with DN. It is now well established that albuminuria stems from disruptions in podocyte structure and function. Podocytes play a major role in the glomerular filtration barrier. The nephrin protein has been identified as a core component of the slit diaphragm in podocytes, and as such, the downregulation of nephrin expression has been described well in various proteinuric glomerulopathies, including DN. Previous studies have shown that the presence of urinary nephrin potentially signifies an early marker of podocyte injury in DN. More recently, there have been increasing bodies of evidence which suggest that circulating autoantibodies targeting nephrin contributes to the pathogenesis of podocytopathies. However, the functional significance of these circulating autoantibodies in patients with DN is not well understood. In this review, we aim to evaluate the significance of nephrin dysregulation in the pathogenesis of DN based on the current available literature and provide an overview on the application of circulating anti-nephrin autoantibodies in relation to its diagnostic as well as prognostic role in podocytopathies, including DN.<\/jats:p>","DOI":"10.3390\/antib14010025","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T07:31:42Z","timestamp":1741764702000},"page":"25","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Is There a Diagnostic and Prognostic Role for Anti-Nephrin Autoantibodies in Diabetic Nephropathy?"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5000-6808","authenticated-orcid":false,"given":"Han Sean","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4561-0844","authenticated-orcid":false,"given":"Henry H. L.","family":"Wu","sequence":"additional","affiliation":[{"name":"Renal Research Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, The University of Sydney, Sydney, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arvind","family":"Ponnusamy","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Lancashire Teaching Hospitals NHS Foundation Trust, Preston PR2 9HT, UK"},{"name":"Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M1 7HR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Alderson","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK"},{"name":"Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M1 7HR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3973-6595","authenticated-orcid":false,"given":"Rajkumar","family":"Chinnadurai","sequence":"additional","affiliation":[{"name":"Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK"},{"name":"Faculty of Biology, Medicine and Health, The University of Manchester, Manchester M1 7HR, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group (2022). KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int., 102, S1\u2013S127.","DOI":"10.1016\/j.kint.2022.06.008"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e269","DOI":"10.1016\/j.amjmed.2019.10.042","article-title":"Albuminuria and Risk of Cardiovascular Events and Mortality in a General Population of Patients with Type 2 Diabetes Without Cardiovascular Disease: A Danish Cohort Study","volume":"133","author":"Fangel","year":"2020","journal-title":"Am. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e2225821","DOI":"10.1001\/jamanetworkopen.2022.25821","article-title":"Association of Albuminuria and Regression of Chronic Kidney Disease in Adults with Newly Diagnosed Moderate to Severe Chronic Kidney Disease","volume":"5","author":"Pasternak","year":"2022","journal-title":"JAMA Netw. Open"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Heyman, S.N., Raz, I., Dwyer, J.P., Weinberg Sibony, R., Lewis, J.B., and Abassi, Z. (2022). Diabetic Proteinuria Revisited: Updated Physiologic Perspectives. Cells, 11.","DOI":"10.3390\/cells11182917"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.4103\/0366-6999.247197","article-title":"Clinicopathological Features of Nondiabetic Renal Diseases from Different Age Groups: An Observational Cross-sectional Study","volume":"131","author":"Liu","year":"2018","journal-title":"Chin. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.krcp.2013.07.002","article-title":"Nondiabetic kidney diseases in type 2 diabetic patients","volume":"32","author":"Kim","year":"2013","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"358","DOI":"10.4103\/0971-4065.103912","article-title":"Nondiabetic kidney disease in type 2 diabetic patients: A single center experience","volume":"22","author":"Das","year":"2012","journal-title":"Indian J. Nephrol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3346\/jkms.2011.26.2.258","article-title":"Cystatin C as an early biomarker of nephropathy in patients with type 2 diabetes","volume":"26","author":"Jeon","year":"2011","journal-title":"J. Korean Med. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1159\/000507858","article-title":"Significance of Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for the Diagnosis of Diabetic Kidney Disease: A Systematic Review and Meta-Analysis","volume":"45","author":"He","year":"2020","journal-title":"Kidney Blood Press. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/ki.2015.314","article-title":"Increased plasma kidney injury molecule-1 suggests early progressive renal decline in non-proteinuric patients with type 1 diabetes","volume":"89","author":"Nowak","year":"2016","journal-title":"Kidney Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1681\/ASN.2011060628","article-title":"Circulating TNF receptors 1 and 2 predict stage 3 CKD in type 1 diabetes","volume":"23","author":"Gohda","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/S1097-2765(00)80057-X","article-title":"Positionally cloned gene for a novel glomerular protein--nephrin--is mutated in congenital nephrotic syndrome","volume":"1","author":"Lenkkeri","year":"1998","journal-title":"Mol. Cell"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"7962","DOI":"10.1073\/pnas.96.14.7962","article-title":"Nephrin is specifically located at the slit diaphragm of glomerular podocytes","volume":"96","author":"Ruotsalainen","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Martin, C.E., and Jones, N. (2018). Nephrin Signaling in the Podocyte: An Updated View of Signal Regulation at the Slit Diaphragm and Beyond. Front. Endocrinol., 9.","DOI":"10.3389\/fendo.2018.00302"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1053\/snep.2002.34724","article-title":"Role of nephrin in renal disease including diabetic nephropathy","volume":"22","author":"Cooper","year":"2002","journal-title":"Semin. Nephrol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2637","DOI":"10.1093\/hmg\/10.23.2637","article-title":"Defective nephrin trafficking caused by missense mutations in the NPHS1 gene: Insight into the mechanisms of congenital nephrotic syndrome","volume":"10","author":"Liu","year":"2001","journal-title":"Hum. Mol. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1038\/labinvest.3780332","article-title":"Changes in the expression of nephrin gene and protein in experimental diabetic nephropathy","volume":"81","author":"Aaltonen","year":"2001","journal-title":"Lab. Investig."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1097\/00004872-200205000-00034","article-title":"Modulation of nephrin in the diabetic kidney: Association with systemic hypertension and increasing albuminuria","volume":"20","author":"Forbes","year":"2002","journal-title":"J. Hypertens."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.2337\/diabetes.52.4.1023","article-title":"Nephrin expression is reduced in human diabetic nephropathy: Evidence for a distinct role for glycated albumin and angiotensin II","volume":"52","author":"Doublier","year":"2003","journal-title":"Diabetes"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Jim, B., Ghanta, M., Qipo, A., Fan, Y., Chuang, P.Y., Cohen, H.W., Abadi, M., Thomas, D.B., and He, J.C. (2012). Dysregulated nephrin in diabetic nephropathy of type 2 diabetes: A cross sectional study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036041"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2969","DOI":"10.2337\/diabetes.52.12.2969","article-title":"Nephrinuria in diabetic nephropathy of type 1 diabetes","volume":"52","author":"Forsblom","year":"2003","journal-title":"Diabetes"},{"key":"ref_22","first-page":"83","article-title":"Urinary nephrin is earlier, more sensitive and specific marker of diabetic nephropathy than microalbuminuria","volume":"39","author":"Kostovska","year":"2020","journal-title":"J. Med. Biochem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1055\/s-0042-1757718","article-title":"Urinary Nephrin is a Sensitive Marker to Predict Early Onset of Nephropathy in Type 2 Diabetes Mellitus","volume":"14","author":"Veluri","year":"2022","journal-title":"J. Lab. Physicians"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1681\/ASN.2021060794","article-title":"Discovery of Autoantibodies Targeting Nephrin in Minimal Change Disease Supports a Novel Autoimmune Etiology","volume":"33","author":"Watts","year":"2022","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"332","DOI":"10.2215\/CJN.05000516","article-title":"Minimal Change Disease","volume":"12","author":"Vivarelli","year":"2017","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2207","DOI":"10.1093\/ndt\/gfu355","article-title":"Permeability factors in idiopathic nephrotic syndrome: Historical perspectives and lessons for the future","volume":"29","author":"Maas","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1172\/JCI7728","article-title":"Nephritogenic mAb 5-1-6 is directed at the extracellular domain of rat nephrin","volume":"104","author":"Topham","year":"1999","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1159\/000479935","article-title":"New Anti-Nephrin Antibody Mediated Podocyte Injury Model Using a C57BL\/6 Mouse Strain","volume":"138","author":"Takeuchi","year":"2018","journal-title":"Nephron"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"710","DOI":"10.2215\/CJN.08500815","article-title":"Anti-CD20 Antibodies for Idiopathic Nephrotic Syndrome in Children","volume":"11","author":"Ravani","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1001\/jamapediatrics.2018.1323","article-title":"Efficacy of Rituximab vs Tacrolimus in Pediatric Corticosteroid-Dependent Nephrotic Syndrome: A Randomized Clinical Trial","volume":"172","author":"Basu","year":"2018","journal-title":"JAMA Pediatr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1056\/NEJMoa2314471","article-title":"Autoantibodies Targeting Nephrin in Podocytopathies","volume":"391","author":"Hengel","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/s41581-024-00873-7","article-title":"Anti-nephrin autoantibodies: A paradigm shift in podocytopathies","volume":"20","author":"Cui","year":"2024","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa0810457","article-title":"M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy","volume":"361","author":"Beck","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1056\/NEJMoa0910500","article-title":"Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis","volume":"363","author":"Pedchenko","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.kint.2023.11.022","article-title":"A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence","volume":"105","author":"Shirai","year":"2024","journal-title":"Kidney Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1093\/ndt\/gfl486","article-title":"Circulating antibodies to nephrin in patients with type 1 diabetes","volume":"22","author":"Aaltonen","year":"2007","journal-title":"Nephrol. Dial. Transplant."}],"container-title":["Antibodies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4468\/14\/1\/25\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:51:17Z","timestamp":1760028677000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4468\/14\/1\/25"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,12]]},"references-count":36,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["antib14010025"],"URL":"https:\/\/doi.org\/10.3390\/antib14010025","relation":{},"ISSN":["2073-4468"],"issn-type":[{"value":"2073-4468","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,12]]}}}