{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T20:00:57Z","timestamp":1786132857652,"version":"build-2736575974"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10","funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SFB\/TRR57 36842431"],"award-info":[{"award-number":["SFB\/TRR57 36842431"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["IRTG2168 272482170"],"award-info":[{"award-number":["IRTG2168 272482170"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["SFB1192 264599542"],"award-info":[{"award-number":["SFB1192 264599542"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["EXC2151 390873048"],"award-info":[{"award-number":["EXC2151 390873048"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003042","name":"Else-Kr\u00f6ner-Fresenius Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003042","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>The advent of second-generation radiofrequency ablation has renewed interest in renal denervation (RDN) to treat patients with drug-resistant arterial hypertension. In this study, we demonstrate that RDN-induced alterations in glomerular perfusion and filtration have hitherto unknown consequences for inflammatory kidney diseases. Denervated kidneys are more susceptible to immune complex GN or endotoxin-induced renal inflammation. In contrast, the improved GFR of denervated kidneys provides relative protection against pyelonephritis, at the cost of higher susceptibility of the contralateral kidney. These effects need to be kept in mind when RDN is considered in patients with hypertension and other conditions. Our findings suggest that unilateral RDN might allow enriching drugs in one kidney.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Renal denervation (RDN) is an invasive intervention to treat drug-resistant arterial hypertension. Its therapeutic value is contentious. Here we examined the effects of RDN on inflammatory and infectious kidney disease models in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Mice were unilaterally or bilaterally denervated, or sham operated, then three disease models were induced: nephrotoxic nephritis (NTN, a model for crescentic GN), pyelonephritis, and acute endotoxemic kidney injury (as a model for septic kidney injury). Analytical methods included measurement of renal glomerular filtration, proteinuria, flow cytometry of renal immune cells, immunofluorescence microscopy, and three-dimensional imaging of optically cleared kidney tissue by light-sheet fluorescence microscopy followed by algorithmic analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Unilateral RDN increased glomerular filtration in denervated kidneys, but decreased it in the contralateral kidneys. In the NTN model, more nephritogenic antibodies were deposited in glomeruli of denervated kidneys, resulting in stronger inflammation and injury in denervated compared with contralateral nondenervated kidneys. Also, intravenously injected LPS increased neutrophil influx and inflammation in the denervated kidneys, both after unilateral and bilateral RDN. When we induced pyelonephritis in bilaterally denervated mice, both kidneys contained less bacteria and neutrophils. In unilaterally denervated mice, pyelonephritis was attenuated and intrarenal neutrophil numbers were lower in the denervated kidneys. The nondenervated contralateral kidneys harbored more bacteria, even compared with sham-operated mice, and showed the strongest influx of neutrophils.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our data suggest that the increased perfusion and filtration in denervated kidneys can profoundly influence concomitant inflammatory diseases. Renal deposition of circulating nephritic material is higher, and hence antibody- and endotoxin-induced kidney injury was aggravated in mice. Pyelonephritis was attenuated in denervated murine kidneys, because the higher glomerular filtration facilitated better flushing of bacteria with the urine, at the expense of contralateral, nondenervated kidneys after unilateral denervation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021010110","type":"journal-article","created":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T15:35:10Z","timestamp":1624030510000},"page":"2445-2453","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":9,"title":["Renal Denervation Exacerbates LPS- and Antibody-induced Acute Kidney Injury, but Protects from Pyelonephritis in Mice"],"prefix":"10.1681","volume":"32","author":[{"given":"Alexander M.C.","family":"B\u00f6hner","sequence":"first","affiliation":[{"name":"Institute for Molecular Medicine and Experimental Immunology, University Hospital of Bonn, Germany"},{"name":"Department of Radiation Oncology, University Hospital of Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice M.","family":"Jacob","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Experimental Immunology, University Hospital of Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1410-7573","authenticated-orcid":false,"given":"Christoph","family":"Heuser","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Experimental Immunology, University Hospital of Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha E.","family":"Stumpf","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Experimental Immunology, University Hospital of Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Effland","sequence":"additional","affiliation":[{"name":"Institute for Applied Mathematics, University of Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeinab","family":"Abdullah","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Experimental Immunology, University Hospital of Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Meyer-Schwesiger","sequence":"additional","affiliation":[{"name":"Institute for Cellular and Integrative Physiology, University Hospital Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"von Vietinghoff","sequence":"additional","affiliation":[{"name":"Nephrology Section, University Hospital of Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6620-2401","authenticated-orcid":false,"given":"Christian","family":"Kurts","sequence":"additional","affiliation":[{"name":"Institute for Molecular Medicine and Experimental Immunology, University Hospital of Bonn, Germany"},{"name":"Department of Microbiology and Immunology, Doherty Institute for Infection and Immunity, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,10]]},"reference":[{"key":"B1-20240826","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1002\/cphy.c100043","article-title":"Neural control of renal function","volume":"1","author":"Johns","year":"2011","journal-title":"Compr Physiol"},{"key":"B2-20240826","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.amjcard.2009.10.027","article-title":"Renal sympathetic denervation and systemic hypertension","volume":"105","author":"Doumas","year":"2010","journal-title":"Am J Cardiol"},{"key":"B3-20240826","first-page":"337","article-title":"Resistant hypertension: An overview","volume":"66","author":"Pedrinelli","year":"2018","journal-title":"Minerva Cardioangiol"},{"key":"B4-20240826","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1161\/HYPERTENSIONAHA.110.163014","article-title":"Catheter-based renal sympathetic denervation for resistant hypertension: Durability of blood pressure reduction out to 24 months","volume":"57","author":"Krum","year":"2011","journal-title":"Hypertension"},{"key":"B5-20240826","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1007\/s00059-012-3689-7","article-title":"Renal denervation: Current state and future perspectives","volume":"37","author":"Kara","year":"2012","journal-title":"Herz"},{"key":"B7-20240826","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1056\/NEJMoa1402670","article-title":"A controlled trial of renal denervation for resistant hypertension","volume":"370","author":"Bhatt","year":"2014","journal-title":"N Engl J Med"},{"key":"B8-20240826","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/s11906-019-1013-0","article-title":"Approaches for the management of resistant hypertension in 2020","volume":"22","author":"Aronow","year":"2020","journal-title":"Curr Hypertens Rep"},{"key":"B9-20240826","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.jash.2016.02.015","article-title":"Evidence for a critical role of the sympathetic nervous system in hypertension","volume":"10","author":"Grassi","year":"2016","journal-title":"J Am Soc Hypertens"},{"key":"B10-20240826","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1016\/j.jcin.2019.02.050","article-title":"Renal denervation for treating hypertension: Current scientific and clinical evidence","volume":"12","author":"Weber","year":"2019","journal-title":"JACC Cardiovasc Interv"},{"key":"B11-20240826","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1016\/j.jacc.2019.04.015","article-title":"Renal denervation update from the International Sympathetic Nervous System Summit: JACC State-of-the-Art Review","volume":"73","author":"Kiuchi","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"B12-20240826","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1016\/S0140-6736(20)30554-7","article-title":"Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): A multicentre, randomised, sham-controlled trial","volume":"395","author":"B\u00f6hm","year":"2020","journal-title":"Lancet"},{"key":"B13-20240826","first-page":"S71","article-title":"Myogenic mechanisms in the kidney","volume":"7","author":"Aukland","year":"1989","journal-title":"J Hypertens Suppl"},{"key":"B14-20240826","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/s12882-017-0586-6","article-title":"The effects of acute renal denervation on kidney perfusion and metabolism in experimental septic shock","volume":"18","author":"Post","year":"2017","journal-title":"BMC Nephrol"},{"key":"B15-20240826","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10286-018-0572-5","article-title":"The renin-angiotensin system in cardiovascular autonomic control: Recent developments and clinical implications","volume":"29","author":"Miller","year":"2019","journal-title":"Clin Auton Res"},{"key":"B16-20240826","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1002\/cphy.c130040","article-title":"Classical renin-angiotensin system in kidney physiology","volume":"4","author":"Sparks","year":"2014","journal-title":"Compr Physiol"},{"key":"B17-20240826","first-page":"40","article-title":"Bidirectional communication between the neuroendocrine system and the immune system: Relevance to health and diseases","volume":"19","author":"ThyagaRajan","year":"2012","journal-title":"Ann Neurosci"},{"key":"B18-20240826","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.cell.2016.04.041","article-title":"Neuro-immune interactions at barrier surfaces","volume":"165","author":"Veiga-Fernandes","year":"2016","journal-title":"Cell"},{"key":"B19-20240826","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.kint.2019.10.032","article-title":"Crosstalk between the nervous system and the kidney","volume":"97","author":"Tanaka","year":"2020","journal-title":"Kidney Int"},{"key":"B20-20240826","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1681\/ASN.2010050548","article-title":"Kidney dendritic cells become pathogenic during crescentic glomerulonephritis with proteinuria","volume":"22","author":"Hochheiser","year":"2011","journal-title":"J Am Soc Nephrol"},{"key":"B21-20240826","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.cellimm.2018.04.009","article-title":"The multifaceted role of the renal mononuclear phagocyte system","volume":"330","author":"Viehmann","year":"2018","journal-title":"Cell Immunol"},{"key":"B22-20240826","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1681\/ASN.2017030270","article-title":"Opposing roles of dendritic cell subsets in experimental GN","volume":"29","author":"Br\u00e4hler","year":"2018","journal-title":"J Am Soc Nephrol"},{"key":"B23-20240826","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1038\/nri3523","article-title":"The immune system and kidney disease: Basic concepts and clinical implications","volume":"13","author":"Kurts","year":"2013","journal-title":"Nat Rev Immunol"},{"key":"B24-20240826","first-page":"23.1","article-title":"Mouse model for pyelonephritis","volume":"Chapter 15","author":"Tittel","year":"2013","journal-title":"Curr Protoc Immunol"},{"key":"B25-20240826","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.lfs.2018.11.061","article-title":"GPR18 expression on PMNs as biomarker for outcome in patient with sepsis","volume":"217","author":"Zhang","year":"2019","journal-title":"Life Sci"},{"key":"B26-20240826","doi-asserted-by":"crossref","first-page":"408","DOI":"10.4049\/jimmunol.1801602","article-title":"An early neutrophil recruitment into the infectious site is critical for bacterial lipoprotein tolerance-afforded protection against microbial sepsis","volume":"204","author":"Chen","year":"2020","journal-title":"J Immunol"},{"key":"B27-20240826","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1681\/ASN.2016020232","article-title":"Fully automated evaluation of total glomerular number and capillary tuft size in nephritic kidneys using lightsheet microscopy","volume":"28","author":"Klingberg","year":"2017","journal-title":"J Am Soc Nephrol"},{"key":"B28-20240826","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat Methods"},{"key":"B29-20240826","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.immuni.2017.01.003","article-title":"CD8+ T cells orchestrate pDC-XCR1+ dendritic cell spatial and functional cooperativity to optimize priming","volume":"46","author":"Brewitz","year":"2017","journal-title":"Immunity"},{"key":"B30-20240826","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1016\/j.celrep.2017.09.082","article-title":"Prolonged IKK\u03b2 inhibition improves ongoing CTL antitumor responses by incapacitating regulatory T cells","volume":"21","author":"Heuser","year":"2017","journal-title":"Cell Rep"},{"key":"B31-20240826","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1681\/ASN.2019121295","article-title":"Unraveling the complexity of the renal mononuclear phagocyte system by genetic cell lineage tracing","volume":"31","author":"B\u00f6hner","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"B32-20240826","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1681\/ASN.2015080873","article-title":"CD103+ kidney dendritic cells protect against crescentic GN by maintaining IL-10-producing regulatory T cells","volume":"27","author":"Evers","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"B33-20240826","doi-asserted-by":"crossref","first-page":"E1064","DOI":"10.3390\/cells8091064","article-title":"Lipocalin-2 (Lcn-2) attenuates polymicrobial sepsis with LPS preconditioning (LPS tolerance) in FcGRIIb deficient lupus mice","volume":"8","author":"Ondee","year":"2019","journal-title":"Cells"},{"key":"B34-20240826","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1681\/ASN.2008050556","article-title":"The IL-23\/Th17 axis contributes to renal injury in experimental glomerulonephritis","volume":"20","author":"Paust","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B35-20240826","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1681\/ASN.2012010040","article-title":"IL-17A production by renal \u03b3\u03b4 T cells promotes kidney injury in crescentic GN","volume":"23","author":"Turner","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"B36-20240826","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1038\/s41581-020-0272-y","article-title":"Kidney dendritic cells: Fundamental biology and functional roles in health and disease","volume":"16","author":"Kurts","year":"2020","journal-title":"Nat Rev Nephrol"},{"key":"B37-20240826","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1038\/nri3712","article-title":"Dendritic cells, monocytes and macrophages: A unified nomenclature based on ontogeny","volume":"14","author":"Guilliams","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B38-20240826","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1093\/cvr\/cvz132","article-title":"Mechanotransduction, immunoregulation, and metabolic functions of CD31 in cardiovascular pathophysiology","volume":"115","author":"Caligiuri","year":"2019","journal-title":"Cardiovasc Res"},{"key":"B39-20240826","doi-asserted-by":"crossref","first-page":"e12483","DOI":"10.1111\/micc.12483","article-title":"Sepsis-induced acute kidney injury: A disease of the microcirculation","volume":"26","author":"Ma","year":"2019","journal-title":"Microcirculation"},{"key":"B40-20240826","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/S0022-3476(98)70018-6","article-title":"Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection","volume":"132","author":"Weirich","year":"1998","journal-title":"J Pediatr"},{"key":"B41-20240826","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.1113\/jphysiol.2013.269654","article-title":"Nociceptive primary afferents: They have a mind of their own","volume":"592","author":"Carlton","year":"2014","journal-title":"J Physiol"},{"key":"B42-20240826","doi-asserted-by":"crossref","first-page":"F822","DOI":"10.1152\/ajprenal.00063.2020","article-title":"Afferent renal innervation in anti-Thy1.1 nephritis in rats","volume":"319","author":"Rodionova","year":"2020","journal-title":"Am J Physiol Renal Physiol"},{"key":"B43-20240826","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.cell.2014.01.006","article-title":"Crosstalk between sentinel and helper macrophages permits neutrophil migration into infected uroepithelium","volume":"156","author":"Schiwon","year":"2014","journal-title":"Cell"},{"key":"B44-20240826","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1007\/BF00779520","article-title":"Efferent nerves of the transplanted reinervated kidney","volume":"51","author":"Lebedev","year":"1961","journal-title":"Bull Exp Biol Med"},{"key":"B45-20240826","first-page":"106","article-title":"Observations on the nature of the enlargement, the regeneration of the nerves, and the function of the canine renal autograft","volume":"32","author":"Couch","year":"1961","journal-title":"Br J Exp Pathol"},{"key":"B46-20240826","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/1523-1747.ep12500043","article-title":"The regeneration of the sympathetic catecholaminergic nerve fibers in the process of burn wound healing in guinea pigs","volume":"32","author":"Kishimoto","year":"1982","journal-title":"J Invest Dermatol"}],"container-title":["Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2021010110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T19:25:05Z","timestamp":1786130705000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.1681\/ASN.2021010110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10]]},"references-count":45,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2021]]}},"URL":"https:\/\/doi.org\/10.1681\/asn.2021010110","relation":{},"ISSN":["1046-6673","1533-3450"],"issn-type":[{"value":"1046-6673","type":"print"},{"value":"1533-3450","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10]]},"assertion":[{"value":"2021-01-27","name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-01","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}