{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T08:12:59Z","timestamp":1787731979526,"version":"build-2784847793"},"reference-count":55,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T00:00:00Z","timestamp":1631750400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mineralocorticoid receptor antagonists (MRA) are drugs with a potentially broad spectrum of action. They have been reported to have healing effects in many diseases, such as chronic heart failure, hypertension, or nephrotic syndrome. Numerous studies suggest that mineralocorticoid receptor activation is pathogenic and a progression factor of chronic kidney disease (CKD); however, results of studies on the use of MRA in the treatment of CKD are inconclusive. Current guidelines recommend against the use of MRA in patients with advanced CKD. Although, there is growing interest on their use in this population due to treatment benefits. In this review, we summarize studies which were purposed to evaluate the impact of MRA therapy on CKD patients. Despite many benefits of this treatment e.g., reducing cardiovascular mortality or alleviating proteinuria, steroidal MRA (such as spironolactone or eplerenone) have a low safety profile. They often lead to hyperkalemia complications which are dangerous in patients with CKD, and diabetic nephropathy, especially in hemodialysis patients. Studies on recently developed nonsteroidal MRA showed that they have fewer side effects. In our review, we discuss steroidal and nonsteroidal MRA treatment effects on the estimated glomerular filtration rate (eGFR), proteinuria, the cardiovascular system, and hyperkalemia in CKD patients. We present new content and recent publications in this field.<\/jats:p>","DOI":"10.3390\/ijms22189995","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T21:38:12Z","timestamp":1631828292000},"page":"9995","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Mineralocorticoid Receptor Antagonists\u2014Use in Chronic Kidney Disease"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2965-0069","authenticated-orcid":false,"given":"Wiktoria","family":"Baran","sequence":"first","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. \u017beromskiego 113, 90-549 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4463-2731","authenticated-orcid":false,"given":"Julia","family":"Krzemi\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. \u017beromskiego 113, 90-549 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5432-3612","authenticated-orcid":false,"given":"Magdalena","family":"Szlagor","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. \u017beromskiego 113, 90-549 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Wronka","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. \u017beromskiego 113, 90-549 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-4746","authenticated-orcid":false,"given":"Ewelina","family":"M\u0142ynarska","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. \u017beromskiego 113, 90-549 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Franczyk","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. \u017beromskiego 113, 90-549 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Rysz","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, ul. \u017beromskiego 113, 90-549 \u0141\u00f3d\u017a, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107701","DOI":"10.1016\/j.pharmthera.2020.107701","article-title":"Mineralocorticoid receptor antagonists in patients with chronic kidney disease","volume":"219","author":"Cosimato","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/eurheartj\/ehaa736","article-title":"Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine","volume":"42","author":"Agarwal","year":"2021","journal-title":"Eur. Heart J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1002\/ddr.21760","article-title":"Role of mineralocorticoid receptor antagonists in kidney diseases","volume":"82","author":"Patel","year":"2020","journal-title":"Drug Dev. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ijcard.2015.05.127","article-title":"Safety profile of mineralocorticoid receptor antagonists: Spironolactone and eplerenone","volume":"200","author":"Lainscak","year":"2015","journal-title":"Int. J. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1097\/FJC.0000000000000091","article-title":"Finerenone, a Novel Selective Nonsteroidal Mineralocorticoid Receptor Antagonist Protects From Rat Cardiorenal Injury","volume":"64","author":"Kolkhof","year":"2014","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_6","first-page":"271","article-title":"Steroidal and Novel Non-steroidal Mineralocorticoid Receptor Antagonists in Heart Failure and Cardiorenal Diseases: Comparison at Bench and Bedside","volume":"243","author":"Kolkhof","year":"2016","journal-title":"Heart Fail."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.kint.2019.02.030","article-title":"Mineralocorticoid receptor antagonists and kidney diseases: Pathophysiological basis","volume":"96","author":"Girerd","year":"2019","journal-title":"Kidney Int."},{"key":"ref_8","unstructured":"National Kidney Foundation (2013). KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int., 3, 5\u201314."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1093\/ndt\/gfl309","article-title":"Microalbuminuria and chronic kidney disease as risk factors for cardiovascular disease","volume":"21","author":"Sarafidis","year":"2006","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.nefro.2015.09.008","article-title":"Beneficial long-term effect of aldosterone antagonist added to a traditional blockade of the renin\u2013angiotensin\u2013aldosterone system among patients with obesity and proteinuria","volume":"35","author":"Morales","year":"2015","journal-title":"Nefrolog\u00eda"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1098","DOI":"10.1007\/s10157-015-1106-2","article-title":"Anti-albuminuric effects of spironolactone in patients with type 2 diabetic nephropathy: A multicenter, randomized clinical trial","volume":"19","author":"Kato","year":"2015","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1097\/HJH.0000000000002187","article-title":"Effects of mineralocorticoid receptor antagonists in proteinuric kidney disease","volume":"37","author":"Alexandrou","year":"2019","journal-title":"J. Hypertens."},{"key":"ref_13","first-page":"CD013165","article-title":"Potassium binders for chronic hyperkalaemia in people with chronic kidney disease","volume":"6","author":"Natale","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1080\/14740338.2018.1462335","article-title":"The tolerability and safety profile of patiromer: A novel polymer-based potassium binder for the treatment of hyperkalemia","volume":"17","author":"Pitt","year":"2018","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yang, C.-T., Kor, C.-T., and Hsieh, Y.-P. (2018). Long-Term Effects of Spironolactone on Kidney Function and Hyperkalemia-Associated Hospitalization in Patients with Chronic Kidney Disease. J. Clin. Med., 7.","DOI":"10.3390\/jcm7110459"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.3892\/etm.2013.1335","article-title":"Effect of spironolactone combined with angiotensin-converting enzyme inhibitors and\/or angiotensin II receptor blockers on chronic glomerular disease","volume":"6","author":"Wang","year":"2013","journal-title":"Exp. Ther. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1177\/1470320313481485","article-title":"Evaluation of spironolactone plus hydrochlorothiazide in reducing proteinuria in type 2 diabetic nephropathy","volume":"16","author":"Momeni","year":"2015","journal-title":"J. Renin-Angiotensin-Aldosterone Syst."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/ejhf.1400","article-title":"Renal function stratified dose comparisons of eplerenone versus placebo in the EMPHASIS-HF trial","volume":"21","author":"Ferreira","year":"2019","journal-title":"Eur. J. Heart Fail."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1585","DOI":"10.1016\/j.jacc.2013.04.086","article-title":"Safety and Efficacy of Eplerenone in Patients at High Risk for Hyperkalemia and\/or Worsening Renal Function: Analyses of the EMPHASIS-HF study subgroups (Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure)","volume":"62","author":"Eschalier","year":"2013","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"940","DOI":"10.2215\/CJN.00240106","article-title":"Selective Aldosterone Blockade with Eplerenone Reduces Albuminuria in Patients with Type 2 Diabetes","volume":"1","author":"Epstein","year":"2006","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1159\/000503713","article-title":"Design and Baseline Characteristics of the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease Trial","volume":"50","author":"Bakris","year":"2019","journal-title":"Am. J. Nephrol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1056\/NEJMoa2025845","article-title":"Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes","volume":"383","author":"Bakris","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1001\/jama.2015.10081","article-title":"Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy","volume":"314","author":"Bakris","year":"2015","journal-title":"JAMA"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.2215\/CJN.06870520","article-title":"Esaxerenone (CS-3150) in Patients with Type 2 Diabetes and Microalbuminuria (ESAX-DN)","volume":"15","author":"Ito","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1007\/s10157-020-01963-z","article-title":"Apararenone in patients with diabetic nephropathy: Results of a randomized, double-blind, placebo-controlled phase 2 dose\u2013response study and open-label extension study","volume":"25","author":"Wada","year":"2021","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"American Diabetes Association 10 (2017). Microvascular Complications and Foot Care:Standards of Medical Care in Diabetes\u20142018. Diabetes Care, 41, S105\u2013S118.","DOI":"10.2337\/dc18-S010"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1053\/j.ajkd.2014.08.001","article-title":"Diabetic Kidney Disease: A Report From an ADA Consensus Conference","volume":"64","author":"Tuttle","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Blankenburg, M., Fett, A.-K., Eisenring, S., Haas, G., and Gay, A. (2019). Patient characteristics and initiation of mineralocorticoid receptor antagonists in patients with chronic kidney disease in routine clinical practice in the US: A retrospective cohort study. BMC Nephrol., 20.","DOI":"10.1186\/s12882-019-1348-4"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Blankenburg, M., Kovesdy, C.P., Fett, A.-K., Griner, R.G., and Gay, A. (2020). Disease characteristics and outcomes in patients with chronic kidney disease and type 2 diabetes: A matched cohort study of spironolactone users and non-users. BMC Nephrol., 21.","DOI":"10.1186\/s12882-020-01719-7"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"16626","DOI":"10.1038\/s41598-020-73638-4","article-title":"The effect of aldosterone and aldosterone blockade on the progression of chronic kidney disease: A randomized placebo-controlled clinical trial","volume":"10","author":"Minakuchi","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/jdi.12629","article-title":"Effects of mineralocorticoid receptor antagonists on the progression of diabetic nephropathy","volume":"8","author":"Sun","year":"2017","journal-title":"J. Diabetes Investig."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2823","DOI":"10.1093\/ndt\/gft281","article-title":"Long-term effects of addition of mineralocorticoid receptor antagonist to angiotensin II receptor blocker in patients with diabetic nephropathy: A randomized clinical trial","volume":"28","author":"Esteghamati","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Currie, G., Taylor, A.H.M., Fujita, T., Ohtsu, H., Lindhardt, M., Rossing, P., Boesby, L., Edwards, N.C., Ferro, C., and Townend, J. (2016). Effect of mineralocorticoid receptor antagonists on proteinuria and progression of chronic kidney disease: A systematic review and meta-analysis. BMC Nephrol., 17.","DOI":"10.1186\/s12882-016-0337-0"},{"key":"ref_34","first-page":"296","article-title":"Predicting albuminuria response to spironolactone treatment with urinary proteomics in patients with type 2 diabetes and hypertension","volume":"33","author":"Lindhardt","year":"2017","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.trsl.2020.04.010","article-title":"Baseline urinary metabolites predict albuminuria response to spironolactone in type 2 diabetes","volume":"222","author":"Mulder","year":"2020","journal-title":"Transl. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S2213-8587(20)30026-7","article-title":"Early detection of diabetic kidney disease by urinary proteomics and subsequent intervention with spironolactone to delay progression (PRIORITY): A prospective observational study and embedded randomised placebo-controlled trial","volume":"8","author":"Tofte","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1053\/j.ajkd.2016.04.011","article-title":"The Safety and Efficacy of Mineralocorticoid Receptor Antagonists in Patients Who Require Dialysis: A Systematic Review and Meta-analysis","volume":"68","author":"Quach","year":"2016","journal-title":"Am. J. Kidney Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1111\/jch.12628","article-title":"Long-Term Effects of Low-Dose Spironolactone on Chronic Dialysis Patients: A Randomized Placebo-Controlled Study","volume":"18","author":"Lin","year":"2016","journal-title":"J. Clin. Hypertens."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1177\/1753944715591448","article-title":"Spironolactone is secure and reduces left ventricular hypertrophy in hemodialysis patients","volume":"9","author":"Bazan","year":"2015","journal-title":"Ther. Adv. Cardiovasc. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1161\/CIRCULATIONAHA.120.051898","article-title":"Finerenone and Cardiovascular Outcomes in Patients With Chronic Kidney Disease and Type 2 Diabetes","volume":"143","author":"Filippatos","year":"2021","journal-title":"Circulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1159\/000503712","article-title":"Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial","volume":"50","author":"Ruilope","year":"2019","journal-title":"Am. J. Nephrol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/ndt\/gft409","article-title":"Rationale and design of the Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease Study (MiREnDa)","volume":"29","author":"Hammer","year":"2014","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1016\/j.kint.2018.11.025","article-title":"A randomized controlled trial of the effect of spironolactone on left ventricular mass in hemodialysis patients","volume":"95","author":"Hammer","year":"2019","journal-title":"Kidney Int."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.amjmed.2017.11.011","article-title":"Effect of Patiromer on Hyperkalemia Recurrence in Older Chronic Kidney Disease Patients Taking RAAS Inhibitors","volume":"131","author":"Weir","year":"2018","journal-title":"Am. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.2215\/CJN.12371214","article-title":"The Safety of Eplerenone in Hemodialysis Patients: A Noninferiority Randomized Controlled Trial","volume":"10","author":"Walsh","year":"2015","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1038\/s41440-019-0270-2","article-title":"Efficacy and safety of dosage-escalation of low-dosage esaxerenone added to a RAS inhibitor in hypertensive patients with type 2 diabetes and albuminuria: A single-arm, open-label study","volume":"42","author":"Itoh","year":"2019","journal-title":"Hypertens. Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1161\/CIRCHEARTFAILURE.114.001104","article-title":"Incidence, Predictors, and Outcomes Related to Hypo- and Hyperkalemia in Patients With Severe Heart Failure Treated With a Mineralocorticoid Receptor Antagonist","volume":"7","author":"Vardeny","year":"2014","journal-title":"Circ. Heart Fail."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/nrneph.2012.217","article-title":"Management of hyperkalaemia consequent to mineralocorticoid-receptor antagonist therapy","volume":"8","author":"Roscioni","year":"2012","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.2337\/diacare.28.9.2106","article-title":"Beneficial Effects of Adding Spironolactone to Recommended Antihypertensive Treatment in Diabetic Nephropathy: A randomized, double-masked, cross-over study","volume":"28","author":"Rossing","year":"2005","journal-title":"Diabetes Care"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1016\/j.kint.2018.08.034","article-title":"Safety and cardiovascular efficacy of spironolactone in dialysis-dependent ESRD (SPin-D): A randomized, placebo-controlled, multiple dosage trial","volume":"95","author":"Charytan","year":"2019","journal-title":"Kidney Int."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1053\/j.ajkd.2007.10.040","article-title":"Change in Proteinuria After Adding Aldosterone Blockers to ACE Inhibitors or Angiotensin Receptor Blockers in CKD: A Systematic Review","volume":"51","author":"Bomback","year":"2008","journal-title":"Am. J. Kidney Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2359","DOI":"10.1093\/ndt\/gfg388","article-title":"Safety of low-dose spironolactone administration in chronic haemodialysis patients","volume":"18","author":"Saudan","year":"2003","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s11897-017-0341-0","article-title":"Treatment of Hyperkalemia in Heart Failure","volume":"14","author":"DeFilippis","year":"2017","journal-title":"Curr. Heart Fail. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1007\/s40264-014-0196-1","article-title":"Drug-Induced Hyperkalemia","volume":"37","author":"Badreddine","year":"2014","journal-title":"Drug Saf."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1056\/NEJMoa1410853","article-title":"Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors","volume":"372","author":"Weir","year":"2015","journal-title":"N. Engl. J. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9995\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:00:29Z","timestamp":1760166029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/18\/9995"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,16]]},"references-count":55,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2021,9]]}},"alternative-id":["ijms22189995"],"URL":"https:\/\/doi.org\/10.3390\/ijms22189995","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,16]]}}}