{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:35:35Z","timestamp":1791462935546,"version":"4.3.4"},"reference-count":86,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T00:00:00Z","timestamp":1696982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["AN372\/30-1"],"award-info":[{"award-number":["AN372\/30-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Calcineurin inhibitors (CNI) can suppress allo- and autoimmunity by suppressing T cell function but also have anti-proteinuric effects by stabilizing the cellular components of the kidney\u2019s filtration barrier. Therefore, CNI are used in autoimmune kidney diseases with proteinuria. However, the traditional CNI, cyclosporine A and tacrolimus, have a narrow therapeutic range, need monitoring of drug levels, and their use is associated with nephrotoxicity and metabolic alterations. Voclosporin (VOC), a novel CNI, no longer requires drug level monitoring and seems to lack these adverse effects, although hypertension and drug\u2013drug interactions still occur. VOC demonstrated efficacy superior to standard-of-care in controlling active lupus nephritis in the phase 2 AURA-LV and the phase 3 AURORA-1 trials and was approved for the treatment of active lupus nephritis. However, how to implement VOC into the current and changing treatment landscape of lupus nephritis is still debated. Here, we review the unique chemistry, pharmacology, and toxicity profile of VOC, summarize the efficacy and safety data from the AURA-LV and AURORA-1 trials, and discuss the following four possible options to implement VOC into the management of lupus nephritis, namely regarding B cell-targeting therapy with belimumab (BEL). These include: 1. patient stratification to either VOC or BEL, 2. VOC\/BEL combination therapy, 3. VOC-BEL sequential therapy, or 4. alternative options for the rapid antiproteinuric effect of VOC.<\/jats:p>","DOI":"10.3390\/cells12202440","type":"journal-article","created":{"date-parts":[[2023,10,12]],"date-time":"2023-10-12T03:07:47Z","timestamp":1697080067000},"page":"2440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Voclosporin: Unique Chemistry, Pharmacology and Toxicity Profile, and Possible Options for Implementation into the Management of Lupus Nephritis"],"prefix":"10.3390","volume":"12","author":[{"given":"Ajinath","family":"Kale","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani 333031, Rajasthan, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3291-0450","authenticated-orcid":false,"given":"Vishwadeep","family":"Shelke","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani 333031, Rajasthan, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Lei","sequence":"additional","affiliation":[{"name":"Division of Diabetology, Department of Internal Medicine IV, Hospital of the Ludwig Maximilians University Munich, 333031 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil Bhanudas","family":"Gaikwad","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Birla Institute of Technology and Science Pilani, Pilani Campus, Pilani 333031, Rajasthan, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2434-2956","authenticated-orcid":false,"given":"Hans-Joachim","family":"Anders","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine IV, Hospital of the Ludwig Maximilians University Munich, 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/164_2021_549","article-title":"A Comprehensive Review of Calcineurin Inhibitors Used for Immunosuppression in Cardiac Transplantation","volume":"272","author":"Engwenyu","year":"2022","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_2","unstructured":"Safarini, O.A., Keshavamurthy, C., and Patel, P. (2022). StatPearls, StatPearls Publishing."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.2215\/CJN.13761119","article-title":"The Evolving Role of Calcineurin Inhibitors in Treating Lupus Nephritis","volume":"15","author":"Peleg","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s00467-020-04695-0","article-title":"Calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene mutations: A systematic review","volume":"36","author":"Malakasioti","year":"2021","journal-title":"Pediatr. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"481","DOI":"10.2215\/CJN.04800908","article-title":"Calcineurin inhibitor nephrotoxicity","volume":"4","author":"Naesens","year":"2009","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"84","DOI":"10.2174\/1389200219666181031113505","article-title":"Metabolic Pathway of Cyclosporine A and Its Correlation with Nephrotoxicity","volume":"20","author":"Wu","year":"2019","journal-title":"Curr. Drug Metab."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1097\/TP.0000000000003350","article-title":"Thirty Years of Tacrolimus in Clinical Practice","volume":"105","author":"Ong","year":"2021","journal-title":"Transplantation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1097\/FTD.0000000000000640","article-title":"Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy: Second Consensus Report","volume":"41","author":"Brunet","year":"2019","journal-title":"Ther. Drug Monit."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1080\/17512433.2022.2092470","article-title":"Voclosporin: A novel calcineurin inhibitor for the treatment of lupus nephritis","volume":"15","author":"Lerma","year":"2022","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1007\/s40265-021-01488-z","article-title":"Voclosporin: First Approval","volume":"81","author":"Heo","year":"2021","journal-title":"Drugs"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, W., Shrivastava, M., Lu, H., and Jiang, Y. (2021). Calcium-calcineurin signaling pathway in Candida albicans: A potential drug target. Microbiol. Res., 249.","DOI":"10.1016\/j.micres.2021.126786"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s12964-020-00636-4","article-title":"Calcineurin","volume":"18","author":"Creamer","year":"2020","journal-title":"Cell Commun. Signal."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/bs.pmbts.2019.06.008","article-title":"Calcineurin signaling as a target for the treatment of alcohol abuse and neuroinflammatory disorders","volume":"167","author":"Ronan","year":"2019","journal-title":"Prog. Mol. Biol. Transl. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Ponticelli, C., Reggiani, F., and Moroni, G. (2021). Old and New Calcineurin Inhibitors in Lupus Nephritis. J. Clin. Med., 10.","DOI":"10.3390\/jcm10214832"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1146\/annurev-med-050311-163340","article-title":"Podocyte biology and pathogenesis of kidney disease","volume":"64","author":"Reiser","year":"2013","journal-title":"Annu. Rev. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1159\/000481633","article-title":"A Review of Podocyte Biology","volume":"47","author":"Garg","year":"2018","journal-title":"Am. J. Nephrol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/s41572-020-0196-7","article-title":"Podocytopathies","volume":"6","author":"Kopp","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"12679","DOI":"10.14814\/phy2.12679","article-title":"Role of calcineurin (CN) in kidney glomerular podocyte: CN inhibitor ameliorated proteinuria by inhibiting the redistribution of CN at the slit diaphragm","volume":"4","author":"Wakamatsu","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"32087","DOI":"10.1038\/srep32087","article-title":"Calcineurin inhibitors cyclosporin A and tacrolimus protect against podocyte injury induced by puromycin aminonucleoside in rodent models","volume":"6","author":"Shen","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/path.5512","article-title":"Calcineurin inhibitors ameliorate PAN-induced podocyte injury through the NFAT-Angptl4 pathway","volume":"252","author":"Shen","year":"2020","journal-title":"J. Pathol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2121","DOI":"10.4155\/fmc.15.78","article-title":"Beyond cyclosporine A: Conformation-dependent passive membrane permeabilities of cyclic peptide natural products","volume":"7","author":"Ahlbach","year":"2015","journal-title":"Future Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"17283","DOI":"10.1038\/s41598-018-35645-4","article-title":"Cyclic undecapeptide Cyclosporin A mediated inhibition of amyloid synthesis: Implications in alleviation of amyloid induced neurotoxicity","volume":"8","author":"Kazmi","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_23","first-page":"46","article-title":"Synthesis of ciclosporin and analogues: Structural and conformational requirements for immunosuppressive activity","volume":"38","author":"Wenger","year":"1986","journal-title":"Prog. Allergy"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13131","DOI":"10.1021\/acs.jmedchem.1c00580","article-title":"Cyclosporin Structure and Permeability: From A to Z and Beyond","volume":"64","author":"Corbett","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.1021\/acs.jpcb.7b12419","article-title":"Conformational Flexibility Is a Determinant of Permeability for Cyclosporin","volume":"122","author":"Wang","year":"2018","journal-title":"J. Phys. Chem. B"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103945","DOI":"10.1016\/j.jddst.2022.103945","article-title":"Recent advances in novel formulation approaches for tacrolimus delivery in treatment of various ocular diseases","volume":"78","author":"Kailasam","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1134\/S0003683820060150","article-title":"Biosynthesis of Tacrolimus by the Streptomyces tsukubensis VKM Ac-2618D Strain in the Presence of Polymeric Sorbents and Development of a Method for Its Isolation and Purification","volume":"56","author":"Solionov","year":"2020","journal-title":"Appl. Biochem. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/ja.2012.28","article-title":"Evaluation, synthesis and characterization of tacrolimus impurities","volume":"65","author":"Ferraboschi","year":"2012","journal-title":"J. Antibiot."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1021\/np9007975","article-title":"Synthesis and characterization of an epimer of tacrolimus, an immunosuppressive drug","volume":"73","author":"Skytte","year":"2010","journal-title":"J. Nat. Prod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1107\/S0907444910051905","article-title":"Structural basis for the cyclophilin A binding affinity and immunosuppressive potency of E-ISA247 (voclosporin)","volume":"67","author":"Kuglstatter","year":"2011","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.2147\/OPTH.S11125","article-title":"Oral voclosporin: Novel calcineurin inhibitor for treatment of noninfectious uveitis","volume":"5","author":"Roesel","year":"2011","journal-title":"Clin. Ophthalmol."},{"key":"ref_32","first-page":"542","article-title":"ISAtx-247 (Isotechnika\/Roche)","volume":"5","author":"Dumont","year":"2004","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_33","first-page":"173","article-title":"Cyclosporine Metabolite Profiles in the Blood of Liver Transplant Patients","volume":"20","author":"Wang","year":"1988","journal-title":"Transplant. Proc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1016\/S0041-1345(01)01929-7","article-title":"Cyclosporine A metabolite AM19 as a potential biomarker in urine for CSA nephropathy","volume":"33","author":"Fobker","year":"2001","journal-title":"Transplant. Proc."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1002\/jcph.166","article-title":"Pharmacokinetics of voclosporin in renal impairment and hepatic impairment","volume":"53","author":"Ling","year":"2013","journal-title":"J. Clin. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3925","DOI":"10.2174\/0929867327666201006153202","article-title":"Cyclosporine A: Chemistry and Toxicity\u2014A Review","volume":"28","author":"Patocka","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_37","first-page":"33","article-title":"Cyclosporin therapeutic drug monitoring\u2014An established service revisited","volume":"24","author":"Morris","year":"2003","journal-title":"Clin. Biochem. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1208\/s12248-013-9500-8","article-title":"Population pharmacokinetics of cyclosporine in transplant recipients","volume":"15","author":"Han","year":"2013","journal-title":"AAPS J."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yang, Y., Li, P., Zhang, Z., Wang, Z., Liu, L., and Liu, X. (2020). Prediction of Cyclosporin-Mediated Drug Interaction Using Physiologically Based Pharmacokinetic Model Characterizing Interplay of Drug Transporters and Enzymes. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197023"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/j.fct.2018.06.054","article-title":"Mechanism of cyclosporine A nephrotoxicity: Oxidative stress, autophagy, and signalings","volume":"118","author":"Wu","year":"2018","journal-title":"Food Chem. Toxicol. Int. J. Publ. Br. Ind. Biol. Res. Assoc."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"588","DOI":"10.3389\/fimmu.2019.00588","article-title":"Lessons to Learn From Low-Dose Cyclosporin-A: A New Approach for Unexpected Clinical Applications","volume":"10","author":"Flores","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e13328","DOI":"10.1111\/petr.13328","article-title":"Pharmacokinetics of tacrolimus granules in pediatric de novo liver, kidney, and heart transplantation: The OPTION study","volume":"23","author":"Webb","year":"2019","journal-title":"Pediatr. Transplant."},{"key":"ref_43","first-page":"Cd009864","article-title":"Topical tacrolimus for atopic dermatitis","volume":"2015","author":"Martins","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"342","DOI":"10.2174\/1389200219666180101104159","article-title":"Tacrolimus\u2014Pharmacokinetic Considerations for Clinicians","volume":"19","author":"Tholking","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"513","DOI":"10.2174\/1389200219666180129151948","article-title":"Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of Tacrolimus in Kidney Transplantation","volume":"19","author":"Yu","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1918","DOI":"10.1111\/bcp.14585","article-title":"Monitoring the tacrolimus concentration in peripheral blood mononuclear cells of kidney transplant recipients","volume":"87","author":"Francke","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e14487","DOI":"10.1111\/ctr.14487","article-title":"De novo tacrolimus extended-release tablets (LCPT) versus twice-daily tacrolimus in adult heart transplantation: Results of a single-center non-inferiority matched control trial","volume":"35","author":"Sam","year":"2021","journal-title":"Clin. Transplant."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1687","DOI":"10.1038\/s41598-018-20071-3","article-title":"Increased Exposure of Tacrolimus by Co-administered Mycophenolate Mofetil: Population Pharmacokinetic Analysis in Healthy Volunteers","volume":"8","author":"Kim","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1097\/01.tp.0000167757.63922.42","article-title":"A prospective, randomized trial of tacrolimus in combination with sirolimus or mycophenolate mofetil in kidney transplantation: Results at 1 year","volume":"80","author":"Mendez","year":"2005","journal-title":"Transplantation"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.biopha.2018.03.054","article-title":"Current progress of tacrolimus dosing in solid organ transplant recipients: Pharmacogenetic considerations","volume":"102","author":"Zhang","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"707","DOI":"10.2165\/00002018-200225100-00003","article-title":"Drug interactions with tacrolimus","volume":"25","year":"2002","journal-title":"Drug Saf."},{"key":"ref_52","first-page":"1","article-title":"Two Decades of Tacrolimus in Renal Transplant: Basic Science and Clinical Evidences","volume":"15","author":"Shrestha","year":"2017","journal-title":"Exp. Clin. Transplant."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1016\/S0140-6736(21)00578-X","article-title":"Efficacy and safety of voclosporin versus placebo for lupus nephritis (AURORA 1): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial","volume":"397","author":"Rovin","year":"2021","journal-title":"Lancet"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1613","DOI":"10.1080\/14656566.2018.1516751","article-title":"An evaluation of voclosporin for the treatment of lupus nephritis","volume":"19","author":"Sin","year":"2018","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1093\/ndt\/gfab022","article-title":"Voclosporin: A novel calcineurin inhibitor with no impact on mycophenolic acid levels in patients with SLE","volume":"37","author":"Huizinga","year":"2022","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.jaad.2005.10.061","article-title":"A randomized, multicenter, double-blind, placebo-controlled phase 2 trial of ISA247 in patients with chronic plaque psoriasis","volume":"54","author":"Bissonnette","year":"2006","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1111\/j.1600-6143.2011.03763.x","article-title":"The PROMISE study: A phase 2b multicenter study of voclosporin (ISA247) versus tacrolimus in de novo kidney transplantation","volume":"11","author":"Busque","year":"2011","journal-title":"Am. J. Transplant."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1016\/j.kint.2021.05.021","article-title":"KDIGO Clinical Practice Guideline for the Management of Glomerular Diseases","volume":"100","author":"Rovin","year":"2021","journal-title":"Kidney Int. Suppl."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1038\/s41577-022-00816-y","article-title":"Glomerulonephritis: Immunopathogenesis and immunotherapy","volume":"23","author":"Anders","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1038\/s41572-021-00303-z","article-title":"Membranous nephropathy","volume":"7","author":"Ronco","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1056\/NEJMoa1814427","article-title":"Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy","volume":"381","author":"Fervenza","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.kint.2020.10.014","article-title":"The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy","volume":"99","author":"Logt","year":"2021","journal-title":"Kidney Int."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1136\/annrheumdis-2020-217178","article-title":"Long-term outcome of a randomised controlled trial comparing tacrolimus with mycophenolate mofetil as induction therapy for active lupus nephritis","volume":"79","author":"Mok","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1136\/annrheumdis-2014-206456","article-title":"Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: A randomised controlled trial and long-term follow-up","volume":"75","author":"Mok","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1089\/jop.2020.0005","article-title":"Calcineurin Inhibitor Voclosporin Preserves Corneal Barrier and Conjunctival Goblet Cells in Experimental Dry Eye","volume":"36","author":"Alam","year":"2020","journal-title":"J. Ocul. Pharmacol. Ther."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1167\/iovs.08-1891","article-title":"LX211 (voclosporin) suppresses experimental uveitis and inhibits human T cells","volume":"50","author":"Cunningham","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Liao, R., Liu, Q., Zheng, Z., Fan, J., Peng, W., Kong, Q., He, H., Yang, S., Chen, W., and Tang, X. (2015). Tacrolimus Protects Podocytes from Injury in Lupus Nephritis Partly by Stabilizing the Cytoskeleton and Inhibiting Podocyte Apoptosis. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0132724"},{"key":"ref_68","first-page":"222","article-title":"Experimental treatment of autoimmune MRL-lpr\/lpr mice with immunosuppressive compound FK506","volume":"69","author":"Yamamoto","year":"1990","journal-title":"Immunology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1136\/annrheumdis-2020-216924","article-title":"2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR\/ERA-EDTA) recommendations for the management of lupus nephritis","volume":"79","author":"Fanouriakis","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41572-019-0141-9","article-title":"Lupus nephritis","volume":"6","author":"Anders","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.kint.2018.08.025","article-title":"A randomized, controlled double-blind study comparing the efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active lupus nephritis","volume":"95","author":"Rovin","year":"2019","journal-title":"Kidney Int."},{"key":"ref_72","first-page":"708","article-title":"Voclosporin Is Effective in Achieving Proteinuria Treatment Targets in Lupus Nephritis Defined by EULAR\/ERA Recommendations","volume":"74","author":"Anders","year":"2022","journal-title":"Arthritis Rheumatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/ndt\/gfab351","article-title":"The management of lupus nephritis as proposed by EULAR\/ERA 2019 versus KDIGO 2021","volume":"38","author":"Anders","year":"2021","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"POSO186","DOI":"10.1136\/annrheumdis-2022-eular.4162","article-title":"Voclosporin for lupus nephritis: Results of the two year AURORA 2 continuation study","volume":"81","author":"Saxena","year":"2022","journal-title":"Ann. Rheum. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"999704","DOI":"10.3389\/fimmu.2022.999704","article-title":"Biological drugs for systemic lupus erythematosus or active lupus nephritis and rates of infectious complications. Evidence from large clinical trials","volume":"13","author":"Steiger","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_76","unstructured":"Parikh, S.V., Arriens, C., Yap, E., Piper, K., Huizinga, R., and Leher, H. (2023). Follow-up Kidney Biopsies from the AURORA 2 Clinical Trial Evaluating Voclosporin for the Treatment of Lupus Nephritis. Clin. Congr. Rheumatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1056\/NEJMoa2001180","article-title":"Two-Year, Randomized, Controlled Trial of Belimumab in Lupus Nephritis","volume":"383","author":"Furie","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1649","DOI":"10.1177\/09612033221131183","article-title":"Safety of belimumab in adult patients with systemic lupus erythematosus: Results of a large integrated analysis of controlled clinical trial data","volume":"31","author":"Wallace","year":"2022","journal-title":"Lupus"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1338","DOI":"10.1093\/ndt\/gfv296","article-title":"Histologic versus clinical remission in proliferative lupus nephritis","volume":"32","author":"Malvar","year":"2017","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.kint.2021.09.012","article-title":"The lupus nephritis management renaissance","volume":"101","author":"Malvar","year":"2022","journal-title":"Kidney Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"980079","DOI":"10.3389\/fimmu.2022.980079","article-title":"Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment","volume":"13","author":"Kirou","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.kint.2021.08.027","article-title":"A secondary analysis of the Belimumab International Study in Lupus Nephritis trial examined effects of belimumab on kidney outcomes and preservation of kidney function in patients with lupus nephritis","volume":"101","author":"Rovin","year":"2022","journal-title":"Kidney Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1093\/ndt\/gfaa329","article-title":"SGLT2 inhibition requires reconsideration of fundamental paradigms in chronic kidney disease, \u2018diabetic nephropathy\u2019, IgA nephropathy and podocytopathies with FSGS lesions","volume":"37","author":"Anders","year":"2022","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1436","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in Patients with Chronic Kidney Disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1056\/NEJMoa2204233","article-title":"Empagliflozin in Patients with Chronic Kidney Disease","volume":"388","author":"Herrington","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"385","DOI":"10.2215\/CJN.13030921","article-title":"The Cost-Effectiveness of Belimumab and Voclosporin for Patients with Lupus Nephritis in the United States","volume":"17","author":"Mandrik","year":"2022","journal-title":"Clin. J. Am. Soc. 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