Inflammatory and lipotoxicity mechanisms in obesity related CKD
| datacite.rights | http://purl.org/coar/access_right/c_abf2 | |
| dc.contributor.author | Rico Fontalvo, Jorge | |
| dc.contributor.author | Raad Sarabia, Maria | |
| dc.contributor.author | Montejo Hernández, Juan | |
| dc.contributor.author | Rodríguez Yanez, Tomas | |
| dc.contributor.author | Caparroso Ramos, Lacides Rafael | |
| dc.contributor.author | Parra Sánchez, Paula | |
| dc.contributor.author | Ovalle Gomez, Ana Alejandra | |
| dc.contributor.author | Jiménez Quintero, Javier | |
| dc.contributor.author | Daza Ornedo, Rodríguez | |
| dc.date.accessioned | 2026-01-19T19:22:14Z | |
| dc.date.available | 2026-01-19T19:22:14Z | |
| dc.date.issued | 2026 | |
| dc.description.abstract | Obesity has been a systemic disease that has been underrecognized for years. Obesity-related chronic kidney disease (Ob-CKD) is a multifaceted disorder that affects patients with CKD to varying degrees. Among the structural changes associated with obesity, obesity-related glomerulopathy (ORG) stands out (glomerular hypertrophy, podocytopathy, mesangial matrix expansion, focal segmental glomerulosclerosis, tubulointerstitial fibrosis, vascular lesions, and tubular atrophy) associated with other kidney diseases. There are direct and indirect mechanisms that affect the kidneys of obese patients. Among the direct mechanisms, several effects may occur: hyperfiltration, activation of the reninangiotensin- aldosterone system (RAAS), inflammation, lipotoxicity, and neurohormonal activation. This is a narrative review that will detail the inflammatory and lipotoxicity mechanisms involved in the genesis of Ob-CKD. | eng |
| dc.format.mimetype | ||
| dc.identifier.citation | Rico-Fontalvo J, Raad-Sarabia M, Montejo Hernández J, Rodríguez Yánez T, Caparroso Ramos LR, Parra Sánchez P, Ovalle Gomez AA, Quintero JJ and Daza-Arnedo R (2026) Inflammatory and lipotoxicity mechanisms in obesity related CKD. Front. Nephrol. 5:1684004. doi: 10.3389/fneph.2025.1684004 | |
| dc.identifier.doi | 10.3389/fneph.2025.1684004 | |
| dc.identifier.issn | 28130626 (Impreso) | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12442/17292 | |
| dc.identifier.url | https://www.frontiersin.org/journals/nephrology/articles/10.3389/fneph.2025.1684004/full | |
| dc.language.iso | eng | |
| dc.publisher | Frontiers Media | spa |
| dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International | eng |
| dc.rights.accessrights | info:eu-repo/semantics/openAccess | |
| dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | |
| dc.source | Frontiers in Nephrology | eng |
| dc.source | Front. Nephrol. | eng |
| dc.source | Vol. 5 No. Año 2026 | spa |
| dc.subject.keywords | Inflammation | eng |
| dc.subject.keywords | Lipotoxicity | eng |
| dc.subject.keywords | Cytokines | eng |
| dc.subject.keywords | Obesity | eng |
| dc.subject.keywords | Chronic kidney disease | eng |
| dc.title | Inflammatory and lipotoxicity mechanisms in obesity related CKD | eng |
| dc.type.driver | info:eu-repo/semantics/article | |
| dc.type.spa | Artículo científico | |
| dcterms.references | Nawaz S, Chinnadurai R, Al-Chalabi S, Evans P, Kalra PA, Syed AA, et al. Obesity and chronic kidney disease: A current review. Obes Sci Pract. (2022) 9:61–74. doi: 10.1002/osp4.629 | eng |
| dcterms.references | Rico-Fontalvo J, Ciudin A, Correa-Rotter R, Dı́az-Crespo FJ, Bonanno C, Lecube A, et al. SEN, SLANH, andSEEDOConsensus report on Obesity related kidney disease. Proposal for a new classification. Kidney Int. (2025) 108:572–83. doi: 10.1016/j.kint.2025.06.013 | eng |
| dcterms.references | Lu JL, Kalantar-Zadeh K, Ma JZ, Quarles LD, Kovesdy CP. Association of body mass index with outcomes in patients with CKD. J Am Soc Nephrol JASN. (2014) 25:2088–96. doi: 10.1681/ASN.2013070754 | eng |
| dcterms.references | Bello AK, Alrukhaimi M, Ashuntantang GE, Basnet S, Rotter RC, Douthat WG, et al. Complications of chronic kidney disease: current state, knowledge gaps, and strategy for action. Kidney Int Suppl. (2017) 7:122–9. doi: 10.1016/j.kisu.2017.07.007 | eng |
| dcterms.references | Aristizábal-Colorado D, Corredor-Rengifo D, Sierra-Castillo S, López-Corredor C, Vernaza-Trujillo DA, Weir-Restrepo D, et al. A decade of progress in type 2 diabetes and cardiovascular disease: advances in SGLT2 inhibitors and GLP-1 receptor agonists – a comprehensive review. Front Endocrinol. (2025) 16:1605746. doi: 10.3389/ fendo.2025.1605746 | eng |
| dcterms.references | Hojs R, Ekart R, Bevc S, Vodošek Hojs N. Chronic kidney disease and obesity. Nephron. (2023) 147:660–4. doi: 10.1159/000531379 | eng |
| dcterms.references | Hall JE. The kidney, hypertension, and obesity. Hypertens Dallas Tex 1979. (2003) 41:625–33. doi: 10.1161/01.HYP.0000052314.95497.78 | eng |
| dcterms.references | Haruhara K, Okabayashi Y, Sasaki T, Kubo E, D’Agati VD, Bertram JF, et al. Podocyte density as a predictor of long-term kidney outcome in obesity-related glomerulopathy. Kidney Int. (2024) 106:496–507. doi: 10.1016/j.kint.2024.05.025 | eng |
| dcterms.references | Hall JE, Mouton AJ, da Silva AA, Omoto ACM, Wang Z, Li X, et al. Obesity, kidney dysfunction, and inflammation: interactions in hypertension. Cardiovasc Res. (2021) 117:1859–76. doi: 10.1093/cvr/cvaa336 | eng |
| dcterms.references | Ellington AA, Malik AR, Klee GG, Turner ST, Rule AD, Mosley TH, et al. Association of plasma resistin with glomerular filtration rate and albuminuria in hypertensive adults. Hypertens Dallas Tex 1979. (2007) 50:708–14. doi: 10.1161/ HYPERTENSIONAHA.107.095257 | eng |
| dcterms.references | Rico-Fontalvo J, Daza-Arnedo R, Rodrı́guez-Yanez T, Osorio W, Suarez- Romero B, Soto O, et al. Obesidad y enfermedad renal crónica. Una mirada desde los mecanismos fisiopatológicos.: Revisión narrativa. Rev Soc Ecuat Nefrol Diálisis Traspl. (2022) 10:97–107. doi: 10.56867/32 | spa |
| dcterms.references | Pereira MJ, Mathioudaki A, Otero AG, Duvvuri PP, Vranic M, Sedigh A, et al. Renal sinus adipose tissue: exploratory study of metabolic features and transcriptome compared with omental and subcutaneous adipose tissue. Obes Silver Spring Md. (2024) 32:1870–84. doi: 10.1002/oby.24114 | eng |
| dcterms.references | Martin-Taboada M, Vila-Bedmar R, Medina-Gómez G. From obesity to chronic kidney disease: how can adipose tissue affect renal function? Nephron. (2021) 145:609– 13. doi: 10.1159/000515418 | eng |
| dcterms.references | Rico-Fontalvo J, Daza-Arnedo R, Montejo-Hernandez J, Cardona-Blanco M, Rodrı́guez-Yanez T. Reflexiones de la enfermedad renal crónica asociada a obesidad: de una vieja relación causal hasta un enfoque basado en la fenotipificación. Rev Soc Ecuat Nefrol Diálisis Traspl. (2022) 10:137–9. doi: 10.56867/37 | spa |
| dcterms.references | Zbrzeźniak-Suszczewicz J, Winiarska A, Perkowska-Ptasińska A, Stompór T. Obesity-related glomerulosclerosis—How adiposity damages the kidneys. Int J Mol Sci. (2025) 26:6247. doi: 10.3390/ijms26136247 | eng |
| dcterms.references | León-Román J, López-Martı́nez M, Esteves A, Ciudin A, Núñez-Delgado S, Á lvarez T, et al. Obesity-related kidney disease: A growing threat to renal health. Int J Mol Sci. (2025) 26:6641. doi: 10.3390/ijms26146641 | eng |
| dcterms.references | D’Agati VD, Chagnac A, de Vries APJ, Levi M, Porrini E, Herman-Edelstein M, et al. Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat Rev Nephrol. (2016) 12:453–71. doi: 10.1038/nrneph.2016.75 | eng |
| dcterms.references | Yang S, Cao C, Deng T, Zhou Z. Obesity-related glomerulopathy: A latent change in obesity requiring more attention. Kidney Blood Press Res. (2020) 45:510–22. doi: 10.1159/000507784 | eng |
| dcterms.references | Daza-Arnedo R, Rico-Fontalvo J, Aroca-Martı́nez G, Rodrı́guez-Yanez T, Martı́nez-Ávila MC, Almanza-Hurtado A, et al. Insulin and the kidneys: a contemporary view on the molecular basis. Front Nephrol. (2023) 3:1133352. doi: 10.3389/fneph.2023.1133352 | eng |
| dcterms.references | Kambham N, Markowitz GS, Valeri AM, Lin J, D’Agati VD. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int. (2001) 59:1498–509. doi: 10.1046/ j.1523-1755.2001.0590041498.x | eng |
| dcterms.references | Tobar A, Ori Y, Benchetrit S, Milo G, Herman-Edelstein M, Zingerman B, et al. Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria. PloS One. (2013) 8:e75547. doi: 10.1371/ journal.pone.0075547 | eng |
| dcterms.references | Chen Y, Dabbas W, Gangemi A, Benedetti E, Lash J, Finn PW, et al. Obesity management and chronic kidney disease. Semin Nephrol. (2021) 41:392–402. doi: 10.1016/j.semnephrol.2021.06.010 | eng |
| dcterms.references | Neeland IJ, Poirier P, Després JP. Cardiovascular and metabolic heterogeneity of obesity: clinical challenges and implications for management. Circulation. (2018) 137:1391–406. doi: 10.1161/CIRCULATIONAHA.117.029617 | eng |
| dcterms.references | Garbarino J, Sturley SL. Saturated with fat: new perspectives on lipotoxicity. Curr Opin Clin Nutr Metab Care. (2009) 12:110–6. doi: 10.1097/MCO.0b013e32832182ee | eng |
| dcterms.references | Sweiss N, Sharma K. Adiponectin effects on the kidney. Best Pract Res Clin Endocrinol Metab. (2014) 28:71–9. doi: 10.1016/j.beem.2013.08.002 | eng |
| dcterms.references | Ren L, Cui H, Wang Y, Ju F, Cai Y, Gang X, et al. The role of lipotoxicity in kidney disease: From molecular mechanisms to therapeutic prospects. BioMed Pharmacother Biomedecine Pharmacother. (2023) 161:114465. doi: 10.1016/ j.biopha.2023.114465 | eng |
| dcterms.references | Opazo-Rı́os L, Mas S, Marı́n-Royo G, Mezzano S, Gómez-Guerrero C, Moreno JA, et al. Lipotoxicity and diabetic nephropathy: novel mechanistic insights and therapeutic opportunities. Int J Mol Sci. (2020) 21:E2632. doi: 10.3390/ijms21072632 | eng |
| dcterms.references | Zhu Q, Scherer PE. Immunologic and endocrine functions of adipose tissue: implications for kidney disease. Nat Rev Nephrol. (2018) 14:105–20. doi: 10.1038/ nrneph.2017.157 | eng |
| dcterms.references | Li LO, Klett EL, Coleman RA. Acyl-CoA synthesis, lipid metabolism and lipotoxicity. Biochim Biophys Acta. (2010) 1801:246–51. doi: 10.1016/ j.bbalip.2009.09.024 | eng |
| dcterms.references | Jorge RF, Rodrigo DA, Tomas RY, Maria Cristina MA, Jose C, Maria Ximena CB, et al. Inflammation and diabetic kidney disease: new perspectives. J BioMed Res Environ Sci. (2022) 3:779–86. doi: 10.37871/jbres1513 | eng |
| dcterms.references | Schelling JR. The contribution of lipotoxicity to diabetic kidney disease. Cells. (2022) 11:3236. doi: 10.3390/cells11203236 | eng |
| dcterms.references | Ali MM, Parveen S, Williams V, Dons R, Uwaifo GI. Cardiometabolic comorbidities and complications of obesity and chronic kidney disease (CKD). J Clin Transl Endocrinol. (2024) 36:100341. doi: 10.1016/j.jcte.2024.100341 | eng |
| dcterms.references | Stasi A, Cosola C, Caggiano G, Cimmarusti MT, Palieri R, Acquaviva PM, et al. Obesity-related chronic kidney disease: principal mechanisms and new approaches in nutritional management. Front Nutr. (2022) 9:925619. doi: 10.3389/fnut.2022.925619 | eng |
| dcterms.references | Wang Y, Liu T, Wu Y, Wang L, Ding S, Hou B, et al. Lipid homeostasis in diabetic kidney disease. Int J Biol Sci. (2024) 20:3710–24. doi: 10.7150/ijbs.95216 | eng |
| dcterms.references | Yoshioka K, Hirakawa Y, Kurano M, Ube Y, Ono Y, Kojima K, et al. Lysophosphatidylcholine mediates fast decline in kidney function in diabetic kidney disease. Kidney Int. (2022) 101:510–26. doi: 10.1016/j.kint.2021.10.039 | eng |
| dcterms.references | Nicholson RJ, Pezzolesi MG, Summers SA. Rotten to the cortex: ceramidemediated lipotoxicity in diabetic kidney disease. Front Endocrinol. (2020) 11:622692. doi: 10.3389/fendo.2020.622692 | eng |
| dcterms.references | Zuo F, Wang Y, Xu X, Ding R, Tang W, Sun Y, et al. CCDC92 deficiency ameliorates podocyte lipotoxicity in diabetic kidney disease. Metabolism. (2024) 150:155724. doi: 10.1016/j.metabol.2023.155724 | eng |
| dcterms.references | Herman-Edelstein M, Scherzer P, Tobar A, Levi M, Gafter U. Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J Lipid Res. (2014) 55:561–72. doi: 10.1194/jlr.P040501 | eng |
| dcterms.references | Chen Y, Deb DK, Fu X, Yi B, Liang Y, Du J, et al. ATP-citrate lyase is an epigenetic regulator to promote obesity-related kidney injury. FASEB J. (2019) 33:9602–15. doi: 10.1096/fj.201900213R | eng |
| dcterms.references | Yamamoto T, Takabatake Y, Takahashi A, Kimura T, Namba T, Matsuda J, et al. High-fat diet-induced lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in the kidney. J Am Soc Nephrol JASN. (2017) 28:1534–51. doi: 10.1681/ ASN.2016070731 | eng |
| dcterms.references | Chae SY, Kim Y, Park CW. Oxidative stress induced by lipotoxicity and renal hypoxia in diabetic kidney disease and possible therapeutic interventions: targeting the lipid metabolism and hypoxia. Antioxid Basel Switz. (2023) 12:2083. doi: 10.3390/ antiox12122083 | eng |
| dcterms.references | Minami S, Sakai S, Yamamoto T, Takabatake Y, Namba-Hamano T, Takahashi A, et al. FGF21 and autophagy coordinately counteract kidney disease progression during aging and obesity. Autophagy. (2024) 20:489–504. doi: 10.1080/ 15548627.2023.2259282 | eng |
| dcterms.references | Fazeli SA, Nourollahi S, Alirezaei A, Mirhashemi S, Davarian A, Hosseini I. Perirenal adipose tissue: clinical implication and therapeutic interventions. Indian J Nephrol. (2024) 34:573–82. doi: 10.25259/ijn_532_23 | eng |
| dcterms.references | Ozbek L, Abdel-Rahman SM, Unlu S, Guldan M, Copur S, Burlacu A, et al. Exploring adiposity and chronic kidney disease: clinical implications, management strategies, prognostic considerations. Med (Mex). (2024) 60:1668. doi: 10.3390/ medicina60101668 | eng |
| dcterms.references | D’Marco L, Salazar J, Cortez M, Salazar M, Wettel M, Lima-Martı́nez M, et al. Perirenal fat thickness is associated with metabolic risk factors in patients with chronic kidney disease. Kidney Res Clin Pract. (2019) 38:365–72. doi: 10.23876/j.krcp.18.0155 | eng |
| dcterms.references | Martinez-Sanchez N, Sweeney O, Sidarta-Oliveira D, Caron A, Stanley SA, Domingos AI. The sympathetic nervous system in the 21st century: Neuroimmune interactions in metabolic homeostasis and obesity. Neuron. (2022) 110:3597–626. doi: 10.1016/j.neuron.2022.10.017 | eng |
| dcterms.references | Ouchi N, Walsh K. Adiponectin as an anti-inflammatory factor. Clin Chim Acta Int J Clin Chem. (2007) 380:24–30. doi: 10.1016/j.cca.2007.01.026 | eng |
| dcterms.references | Vilariño-Garcı́a T, Polonio-González ML, Pérez-Pérez A, Ribalta J, Arrieta F, Aguilar M, et al. Role of leptin in obesity, cardiovascular disease, and type 2 diabetes. Int J Mol Sci. (2024) 25:2338. doi: 10.3390/ijms25042338 | eng |
| dcterms.references | Selvarajah V, Robertson D, Hansen L, Jermutus L, Smith K, Coggi A, et al. A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease. Kidney Int. (2024) 106:1170–80. doi: 10.1016/j.kint.2024.08.023 | eng |
| dcterms.references | Radwan RM, Lee YA, Kotecha P, Wright DR, Hernandez I, Ramon R, et al. Regional trends and disparities in newer GLP1 receptor agonist initiation among realworld adult patients eligible for obesity treatment. Diabetes Obes Metab. (2025) 27:3113–23. doi: 10.1111/dom.16318 | eng |
| dcterms.references | Al-Ozairi E, Narula K, Miras AD, Taghadom E, Samad AE, Al Kandari J, et al. Obesity Treatments to Improve Type 1 Diabetes (OTID): a randomized controlled trial of the combination of glucagon-like peptide 1 analogues and sodium-glucose cotransporter 2 inhibitors-protocol for Obesity Treatments to Improve Type 1 Diabetes (the OTID trial). Trials. (2024) 25:129. doi: 10.1186/s13063-024-07930-3 | eng |
| dcterms.references | Patel R, Wadid M, Makwana B, Kumar A, Khadke S, Bhatti A, et al. GLP-1 receptor agonists among patients with overweight or obesity, diabetes, and HFpEF on SGLT2 inhibitors. JACC Heart Fail. (2024) 12:1814–26. doi: 10.1016/j.jchf.2024.07.006 | eng |
| dcterms.references | Gourdy P, Darmon P, Dievart F, Halimi JM, Guerci B. Combining glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) in patients with type 2 diabetes mellitus (T2DM). Cardiovasc Diabetol. (2023) 22:79. doi: 10.1186/s12933-023-01798-4 | eng |
| dcterms.references | Aristizábal-Colorado D, Ocampo-Posada M, Rivera-Martı́nez WA, Corredor- Rengifo D, Rico-Fontalvo J, Gómez-Mesa JE, et al. SGLT2 inhibitors and how they work beyond the glucosuric effect. State of the art. Am J Cardiovasc Drugs Drugs Devices Interv. (2024) 24:707–18. doi: 10.1007/s40256-024-00673-1 | eng |
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