{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:32Z","timestamp":1791331232132,"version":"4.3.1"},"reference-count":49,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T00:00:00Z","timestamp":1617667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research program, University Medical Center, University of G\u00f6ttingen","award":["1403720"],"award-info":[{"award-number":["1403720"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Renal involvement is a common and severe complication of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), potentially resulting in a pauci-immune necrotizing and crescentic ANCA glomerulonephritis (GN) with acute kidney injury (AKI), end-stage renal disease (ESRD) or death. There is recent evidence that the degree of proteinuria at diagnosis is associated with long-term renal outcome in ANCA GN. Therefore, we here aimed to systematically describe the association between proteinuria and clinicopathological characteristics in 53 renal biopsies with ANCA GN and corresponding urinary samples at admission. Methods: A total number of 53 urinary samples at admission and corresponding renal biopsies with confirmed renal involvement of AAV were retrospectively included from 2015 to 2021 in a single-center study. Results: Proteinuria correlated with myeloperoxidase (MPO) subtype, diagnosis of microscopic polyangiitis (MPA) and severe deterioration of kidney function. Proteinuria was most prominent in sclerotic class ANCA GN and ANCA renal risk score (ARRS) high risk attributed to nonselective proteinuria, including both glomerular and tubular proteinuria. Finally, there was no association between proteinuria and systemic disease activity, suggesting that proteinuria reflected specific renal involvement in AAV rather that systemic disease activity. Conclusions: In conclusion, proteinuria correlated with distinct clinicopathological characteristics in ANCA GN, mostly attributed to a reduced fraction of normal glomeruli. Furthermore, proteinuria in ANCA GN reflected specific renal involvement in AAV rather than systemic disease activity. Therefore, urinary findings could further improve our understanding of mechanisms promoting kidney injury and progression of ANCA GN.<\/jats:p>","DOI":"10.3390\/jcm10071538","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T10:34:12Z","timestamp":1617705252000},"page":"1538","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Proteinuria Indicates Decreased Normal Glomeruli in ANCA-Associated Glomerulonephritis Independent of Systemic Disease Activity"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8724-4803","authenticated-orcid":false,"given":"D\u00e9sir\u00e9e","family":"Tampe","sequence":"first","affiliation":[{"name":"Department of Nephrology and Rheumatology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6065-5680","authenticated-orcid":false,"given":"Peter","family":"Korsten","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Str\u00f6bel","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2843-3567","authenticated-orcid":false,"given":"Samy","family":"Hakroush","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4357-9863","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Tampe","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, University Medical Center G\u00f6ttingen, 37075 G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/art.37715","article-title":"2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides","volume":"65","author":"Jennette","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1053\/j.ajkd.2015.03.025","article-title":"Characteristics and Outcomes of Granulomatosis With Polyangiitis (Wegener) and Microscopic Polyangiitis Requiring Renal Replacement Therapy: Results From the European Renal Association-European Dialysis and Transplant Association Registry","volume":"66","author":"Hruskova","year":"2015","journal-title":"Am. J. Kidney Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13613-017-0262-9","article-title":"Patients with ANCA-associated vasculitis admitted to the intensive care unit with acute vasculitis manifestations: A retrospective and comparative multicentric study","volume":"7","author":"Demiselle","year":"2017","journal-title":"Ann. Intensive Care"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1751","DOI":"10.1046\/j.1523-1755.1999.00758.x","article-title":"Kidney biopsy as a predictor for renal outcome in ANCA-associated necrotizing glomerulonephritis","volume":"56","author":"Bajema","year":"1999","journal-title":"Kidney Int."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1046\/j.1523-1755.2002.00605.x","article-title":"Determinants of outcome in ANCA-associated glomerulonephritis: A prospective clinico-histopathological analysis of 96 patients","volume":"62","author":"Hauer","year":"2002","journal-title":"Kidney Int."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1681\/ASN.2005080870","article-title":"Clinical and histologic determinants of renal outcome in ANCA-associated vasculitis: A prospective analysis of 100 patients with severe renal involvement","volume":"17","author":"Hauer","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1989","DOI":"10.1093\/oxfordjournals.ndt.a027086","article-title":"The renal histopathology in systemic vasculitis: An international survey study of inter- and intra-observer agreement","volume":"11","author":"Bajema","year":"1996","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1681\/ASN.2010050477","article-title":"Histopathologic classification of ANCA-associated glomerulonephritis","volume":"21","author":"Berden","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2343","DOI":"10.1093\/ndt\/gfr643","article-title":"Re-evaluation of the histopathologic classification of ANCA-associated glomerulonephritis: A study of 121 patients in a single center","volume":"27","author":"Chang","year":"2012","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Ellis, C.L., Manno, R.L., Havill, J.P., Racusen, L.C., and Geetha, D. (2013). Validation of the new classification of pauci-immune glomerulonephritis in a United States cohort and its correlation with renal outcome. BMC Nephrol., 14.","DOI":"10.1186\/1471-2369-14-210"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Togashi, M., Komatsuda, A., Nara, M., Omokawa, A., Okuyama, S., Sawada, K., and Wakui, H. (2013). Validation of the 2010 histopathological classification of ANCA-associated glomerulonephritis in a Japanese single-center cohort. Mod. Rheumatol.","DOI":"10.1007\/s10165-013-0877-0"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1097\/01.mnh.0000444818.95496.a4","article-title":"Histopathological classification of antineutrophil cytoplasmic antibody-associated glomerulonephritis: An update","volume":"23","author":"Rahmattulla","year":"2014","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"905","DOI":"10.2215\/CJN.08290813","article-title":"Predictors of treatment outcomes in ANCA-associated vasculitis with severe kidney failure","volume":"9","author":"Lee","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.humpath.2016.01.015","article-title":"The predictive value of kidney biopsy in renal vasculitis: A multicenter cohort study","volume":"52","author":"Villacorta","year":"2016","journal-title":"Hum. Pathol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1016\/j.humpath.2014.02.017","article-title":"Validation of a histopathologic classification scheme for antineutrophil cytoplasmic antibody-associated glomerulonephritis","volume":"45","author":"Nohr","year":"2014","journal-title":"Hum. Pathol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1684","DOI":"10.2215\/CJN.01210214","article-title":"The new histopathologic classification of ANCA-associated GN and its association with renal outcomes in childhood","volume":"9","author":"Noone","year":"2014","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1093\/ndt\/gfu084","article-title":"ANCA serotype and histopathological classification for the prediction of renal outcome in ANCA-associated glomerulonephritis","volume":"29","author":"Quintana","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1681\/ASN.2012090912","article-title":"Estimating renal survival using the ANCA-associated GN classification","volume":"24","author":"Hilhorst","year":"2013","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Iwakiri, T., Fujimoto, S., Kitagawa, K., Furuichi, K., Yamahana, J., Matsuura, Y., Yamashita, A., Uezono, S., Shimao, Y., and Hisanaga, S. (2013). Validation of a newly proposed histopathological classification in Japanese patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis. BMC Nephrol., 14.","DOI":"10.1186\/1471-2369-14-125"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1053\/j.ajkd.2013.08.025","article-title":"Histopathologic and clinical predictors of kidney outcomes in ANCA-associated vasculitis","volume":"63","author":"Ford","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1007\/s00296-014-3041-z","article-title":"Histopathological classification of pauci-immune glomerulonephritis and its impact on outcome","volume":"34","author":"Naidu","year":"2014","journal-title":"Rheumatol. Int."},{"key":"ref_22","first-page":"S56","article-title":"Predictors of renal survival in ANCA-associated vasculitis. Validation of a histopatological classification schema and review of the literature","volume":"33","author":"Moroni","year":"2015","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Andreiana, I., Stancu, S., Avram, A., Taran, L., and Mircescu, G. (2015). ANCA positive crescentic glomerulonephritis outcome in a Central East European cohort: A retrospective study. BMC Nephrol., 16.","DOI":"10.1186\/s12882-015-0091-8"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1093\/ndt\/gfu237","article-title":"Long-term outcome of anti-neutrophil cytoplasm antibody-associated glomerulonephritis: Evaluation of the international histological classification and other prognostic factors","volume":"30","author":"Tanna","year":"2015","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1805","DOI":"10.1007\/s10067-016-3195-z","article-title":"Clinical presentation and outcome prediction of clinical, serological, and histopathological classification schemes in ANCA-associated vasculitis with renal involvement","volume":"35","year":"2016","journal-title":"Clin. Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"i31","DOI":"10.1093\/ndt\/gfv035","article-title":"Twenty-five years of RENHIS: A history of histopathological studies within EUVAS","volume":"30","author":"Ferrario","year":"2015","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.2215\/CJN.04800516","article-title":"Prognostic Value of Histologic Classification of ANCA-Associated Glomerulonephritis","volume":"11","author":"Bjorneklett","year":"2016","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"304","DOI":"10.3899\/jrheum.160866","article-title":"Histopathological Classification and Renal Outcome in Patients with Antineutrophil Cytoplasmic Antibodies-associated Renal Vasculitis: A Study of 186 Patients and Metaanalysis","volume":"44","author":"Chen","year":"2017","journal-title":"J. Rheumatol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1016\/j.kint.2018.07.020","article-title":"Development and validation of a renal risk score in ANCA-associated glomerulonephritis","volume":"94","author":"Brix","year":"2018","journal-title":"Kidney Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1093\/ndt\/gfh563","article-title":"Histological and clinical predictors of early and late renal outcome in ANCA-associated vasculitis","volume":"20","author":"Neumann","year":"2005","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1681\/ASN.V9101915","article-title":"Determinants of renal outcome in anti-myeloperoxidase-associated necrotizing crescentic glomerulonephritis","volume":"9","author":"Franssen","year":"1998","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"622028","DOI":"10.3389\/fmed.2020.622028","article-title":"Histopathological findings predict renal recovery in severe ANCA-associated vasculitis requiring intensive care treatment","volume":"7","author":"Hakroush","year":"2020","journal-title":"Front. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.3389\/fimmu.2019.01405","article-title":"Podocytes and Proteinuria in ANCA-Associated Glomerulonephritis: A Case-Control Study","volume":"10","author":"Neeskens","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"Levey","year":"2009","journal-title":"Ann. Intern. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1136\/ard.2008.101279","article-title":"Modification and validation of the Birmingham Vasculitis Activity Score (version 3)","volume":"68","author":"Mukhtyar","year":"2009","journal-title":"Ann. Rheum. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/ki.2010.165","article-title":"Normalization of urinary biomarkers to creatinine during changes in glomerular filtration rate","volume":"78","author":"Waikar","year":"2010","journal-title":"Kidney Int."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"186","DOI":"10.7326\/0003-4819-98-2-186","article-title":"Proteinuria: Diagnostic principles and procedures","volume":"98","author":"Abuelo","year":"1983","journal-title":"Ann. Intern. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.amjhyper.2007.01.010","article-title":"Alpha-1 microglobulin as a new inflammatory marker in newly diagnosed hypertensive patients","volume":"20","author":"Vyssoulis","year":"2007","journal-title":"Am. J. Hypertens."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1080\/00365517609055274","article-title":"Progression of nephropathy in long-term diabetics with proteinuria and effect of initial anti-hypertensive treatment","volume":"36","author":"Mogensen","year":"1976","journal-title":"Scand. J. Clin. Lab. Investig."},{"key":"ref_40","first-page":"207","article-title":"Membranous nephropathy long-term follow-up and association with neoplasia","volume":"44","author":"Row","year":"1975","journal-title":"QJM Int. J. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1159\/000168199","article-title":"Proteinuria and progression in human glomerular diseases","volume":"10","author":"Cameron","year":"1990","journal-title":"Am. J. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1007\/BF02374501","article-title":"The course of kidney function in type 2 (non-insulin-dependent) diabetic patients with diabetic nephropathy","volume":"36","author":"Gall","year":"1993","journal-title":"Diabetologia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1056\/NEJM199311113292004","article-title":"The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group","volume":"329","author":"Lewis","year":"1993","journal-title":"N. Engl. J. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/ki.1995.246","article-title":"Progression of overt nephropathy in non-insulin-dependent diabetes","volume":"47","author":"Myers","year":"1995","journal-title":"Kidney Int."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1046\/j.1464-5491.1999.00063.x","article-title":"Natural course of kidney function in Type 2 diabetic patients with diabetic nephropathy","volume":"16","author":"Christensen","year":"1999","journal-title":"Diabet. Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/ncpneph0915","article-title":"Remission of proteinuria in primary glomerulonephritis: We know the goal but do we know the price?","volume":"4","author":"Philibert","year":"2008","journal-title":"Nat. Clin. Pract. Nephrol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1093\/clinchem\/37.5.621","article-title":"Albuminuria vs urinary total protein for detecting chronic renal disorders","volume":"37","author":"Shihabi","year":"1991","journal-title":"Clin. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1093\/ndt\/gfu042","article-title":"Repeat protocol renal biopsy in ANCA-associated renal vasculitis","volume":"29","author":"Hruskova","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1080\/0886022X.2018.1487865","article-title":"Clinical and pathologic characteristics of pauci-immune anti-myeloperoxidase antibody associated glomerulonephritis with nephrotic range proteinuria","volume":"40","author":"Xu","year":"2018","journal-title":"Ren. Fail."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/7\/1538\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:11:26Z","timestamp":1760364686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/7\/1538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,6]]},"references-count":49,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,4]]}},"alternative-id":["jcm10071538"],"URL":"https:\/\/doi.org\/10.3390\/jcm10071538","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,6]]}}}