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image of Molecular Insight into Obesity-Associated Nephropathy: Clinical Implications and Possible Strategies for its Management

Abstract

Obesity is a significant health concern due to its rapid increase worldwide. It has been linked to the pathogenic factors of renal diseases, cancer, cardiovascular diseases, hypertension, dyslipidemia, and type 2 diabetes. Notably, obesity raises the likelihood of developing chronic kidney disease (CKD), leading to higher adult mortality and morbidity rates. This study explores the molecular mechanisms that underlie obesity-associated nephropathy and its clinical implications. Obesity-Associated Nephropathy (OAN) develops and worsens due to insulin resistance and hyperinsulinemia, which promote renal sodium reabsorption, glomerular hyperfiltration, and hypertension, leading to progressive kidney damage. Renal damage is further aggravated by persistent inflammation and redox damage, mediated by adipokines and proinflammatory cytokines, such as TNF-α and IL-6. Furthermore, stimulation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) intensifies glomerular hypertension and fibrosis. These elements cause glomerular hyperfiltration, renal hypertrophy, and progressive kidney damage. Clinical manifestations of obesity-associated nephropathy include proteinuria, reduced glomerular filtration rate (GFR), and ultimately, CKD. Management strategies currently focus on lifestyle modifications, such as weight loss through diet and exercise, which have been effective in reducing proteinuria and improving GFR. Pharmacological treatments targeting metabolic pathways, including GLP-1 receptor agonists and SGLT2 inhibitors, have shown renoprotective properties. Additionally, traditional RAAS inhibitors offer therapeutic benefits. Early detection and comprehensive management of OAN are essential to prevent its progression and lessen the burden of CKD.

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2024-10-14
2024-11-14

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References

  1. Consultation W.H.O.E. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004 363 9403 157 163 10.1016/S0140‑6736(03)15268‑3 14726171
    [Google Scholar]
  2. Tavassoly I. Barbieri V. van Hasselt C. Martinez P. Sobie E.A. Hansen J. Azeloglu E. Goldfarb J. Sanseau P. Rajpal D.K. Iyengar R. A tissue-and organ-based cell biological atlas of obesity-related human genes and cellular pathways. bioRxiv 2020 10.1101/2020.03.16.993824
    [Google Scholar]
  3. Consultation W.H. Obesity: Preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ. Tech. Rep. Ser. 2000 894 i xii, 1-253 11234459
    [Google Scholar]
  4. El Nahas A.M. Bello A.K. Chronic kidney disease: The global challenge. Lancet 2005 365 9456 331 340 10.1016/S0140‑6736(05)17789‑7 15664230
    [Google Scholar]
  5. Li P.K. Burdmann E.A. Mehta R.L. Acute kidney injury: Global health alert. Arab J. Nephrol. Transplant. 2013 6 2 75 81 23795368
    [Google Scholar]
  6. Preble W. Obesity: Observations on one thousand cases. Boston Med. Surg. J. 1923 188 17 617 621 10.1056/NEJM192304261881701
    [Google Scholar]
  7. Hsu C. McCulloch C.E. Iribarren C. Darbinian J. Go A.S. Body mass index and risk for end-stage renal disease. Ann. Intern. Med. 2006 144 1 21 28 10.7326/0003‑4819‑144‑1‑200601030‑00006 16389251
    [Google Scholar]
  8. Alizadeh S. Esmaeili H. Alizadeh M. Daneshzad E. Sharifi L. Radfar H. Radaei M.K. Metabolic phenotypes of obese, overweight, and normal weight individuals and risk of chronic kidney disease: a systematic review and meta-analysis. Arch. Endocrinol. Metab. 2019 63 4 427 437 10.20945/2359‑3997000000149 31365625
    [Google Scholar]
  9. Maalouf N.M. Sakhaee K. Parks J.H. Coe F.L. Adams-Huet B. Pak C.Y.C. Association of urinary pH with body weight in nephrolithiasis. Kidney Int. 2004 65 4 1422 1425 10.1111/j.1523‑1755.2004.00522.x 15086484
    [Google Scholar]
  10. Siener R. Glatz S. Nicolay C. Hesse A. The role of overweight and obesity in calcium oxalate stone formation. Obes. Res. 2004 12 1 106 113 10.1038/oby.2004.14 14742848
    [Google Scholar]
  11. Tessaro C.Z.W. Ramos C.I. Heilberg I.P. Influence of nutritional status, laboratory parameters and dietary patterns upon urinary acid excretion in calcium stone formers. J. Bras. Nefrol. 2018 40 1 35 43 10.1590/2175‑8239‑jbn‑3814 29796583
    [Google Scholar]
  12. Poore W. Boyd C.J. Singh N.P. Wood K. Gower B. Assimos D.G. Obesity and its impact on kidney stone formation. Rev. Urol. 2020 22 1 17 23 32523467
    [Google Scholar]
  13. Fox C.S. Larson M.G. Leip E.P. Culleton B. Wilson P.W. Levy D. Predictors of new-onset kidney disease in a community-based population. JAMA 2004 291 7 844 850 10.1001/jama.291.7.844 14970063
    [Google Scholar]
  14. Johnson R.J. Sanchez-Lozada L.G. Nakagawa T. The effect of fructose on renal biology and disease. J. Am. Soc. Nephrol. 2010 21 12 2036 2039 10.1681/ASN.2010050506 21115612
    [Google Scholar]
  15. Aston L.M. Glycaemic index and metabolic disease risk. Proc. Nutr. Soc. 2006 65 1 125 134 10.1079/PNS2005485 16441952
    [Google Scholar]
  16. Rüster C Wolf G The role of the renin-angiotensin-aldosterone system in obesity-related renal diseases. Semin Nephrol. 2013 33 1 44 53 10.1016/j.semnephrol.2012.12.002
    [Google Scholar]
  17. Rubin-Kelley V.E. Jevnikar A.M. Antigen presentation by renal tubular epithelial cells. J. Am. Soc. Nephrol. 1991 2 1 13 26 10.1681/ASN.V2113 1912411
    [Google Scholar]
  18. Declèves A.E. Mathew A.V. Cunard R. Sharma K. AMPK mediates the initiation of kidney disease induced by a high-fat diet. J. Am. Soc. Nephrol. 2011 22 10 1846 1855 10.1681/ASN.2011010026 21921143
    [Google Scholar]
  19. Chen S. Zhou S. Wu B. Zhao Y. Liu X. Liang Y. Shao X. Holthöfer H. Zou H. Association between metabolically unhealthy overweight/obesity and chronic kidney disease: The role of inflammation. Diabetes Metab. 2014 40 6 423 430 10.1016/j.diabet.2014.08.005 25451190
    [Google Scholar]
  20. Wang H. Li J. Gai Z. Kullak-Ublick G.A. Liu Z. TNF-α deficiency prevents renal inflammation and oxidative stress in obese mice. Kidney Blood Press. Res. 2017 42 3 416 427 10.1159/000478869 28683439
    [Google Scholar]
  21. Wen Y. Lu X. Ren J. Privratsky J.R. Yang B. Rudemiller N.P. Zhang J. Griffiths R. Jain M.K. Nedospasov S.A. Liu B.C. Crowley S.D. KLF4 in macrophages attenuates TNFα-mediated kidney injury and fibrosis. J. Am. Soc. Nephrol. 2019 30 10 1925 1938 10.1681/ASN.2019020111 31337692
    [Google Scholar]
  22. Therrien F.J. Agharazii M. Lebel M. Larivière R. Neutralization of tumor necrosis factor-alpha reduces renal fibrosis and hypertension in rats with renal failure. Am. J. Nephrol. 2012 36 2 151 161 10.1159/000340033 22813949
    [Google Scholar]
  23. Eo H. Park J.E. Jeon Y. Lim Y. Ameliorative effect of ecklonia cava polyphenol extract on renal inflammation associated with aberrant energy metabolism and oxidative stress in high fat diet-induced obese mice. J. Agric. Food Chem. 2017 65 19 3811 3818 10.1021/acs.jafc.7b00357 28459555
    [Google Scholar]
  24. Kizer J.R. Adiponectin, cardiovascular disease, and mortality: Parsing the dual prognostic implications of a complex adipokine. Metabolism 2014 63 9 1079 1083 10.1016/j.metabol.2014.06.011 25038728
    [Google Scholar]
  25. Song S.H. Oh T.R. Choi H.S. Kim C.S. Ma S.K. Oh K.H. Ahn C. Kim S.W. Bae E.H. High serum adiponectin as a biomarker of renal dysfunction: Results from the KNOW-CKD study. Sci. Rep. 2020 10 1 5598 10.1038/s41598‑020‑62465‑2 32221363
    [Google Scholar]
  26. Kim-Mitsuyama S. Soejima H. Yasuda O. Node K. Jinnouchi H. Yamamoto E. Sekigami T. Ogawa H. Matsui K. Total adiponectin is associated with incident cardiovascular and renal events in treated hypertensive patients: subanalysis of the ATTEMPT-CVD randomized trial. Sci. Rep. 2019 9 1 16589 10.1038/s41598‑019‑52977‑x 31719604
    [Google Scholar]
  27. Jia T. Carrero J.J. Lindholm B. Stenvinkel P. The complex role of adiponectin in chronic kidney disease. Biochimie 2012 94 10 2150 2156 10.1016/j.biochi.2012.02.024 22980197
    [Google Scholar]
  28. Kim Y. Park C.W. Mechanisms of adiponectin action: Implication of adiponectin receptor agonism in diabetic kidney disease. Int. J. Mol. Sci. 2019 20 7 1782 10.3390/ijms20071782 30974901
    [Google Scholar]
  29. La Russa D. Marrone A. Mandalà M. Macirella R. Pellegrino D. Antioxidant/anti-inflammatory effects of caloric restriction in an aged and obese rat model: The role of adiponectin. Biomedicines 2020 8 12 532 10.3390/biomedicines8120532 33255520
    [Google Scholar]
  30. Câmara N.O.S. Iseki K. Kramer H. Liu Z.H. Sharma K. Kidney disease and obesity: Epidemiology, mechanisms and treatment. Nat. Rev. Nephrol. 2017 13 3 181 190 10.1038/nrneph.2016.191 28090083
    [Google Scholar]
  31. McArdle M.A. Finucane O.M. Connaughton R.M. McMorrow A.M. Roche H.M. Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies. Front. Endocrinol. (Lausanne) 2013 4 52 10.3389/fendo.2013.00052 23675368
    [Google Scholar]
  32. Ahmad I. Zelnick L.R. Robinson N.R. Hung A.M. Kestenbaum B. Utzschneider K.M. Kahn S.E. de Boer I.H. Chronic kidney disease and obesity bias surrogate estimates of insulin sensitivity compared with the hyperinsulinemic euglycemic clamp. Am. J. Physiol. Endocrinol. Metab. 2017 312 3 E175 E182 10.1152/ajpendo.00394.2016 28073780
    [Google Scholar]
  33. de Boer I.H. Zelnick L. Afkarian M. Ayers E. Curtin L. Himmelfarb J. Ikizler T.A. Kahn S.E. Kestenbaum B. Utzschneider K. Impaired glucose and insulin homeostasis in moderate-severe CKD. J. Am. Soc. Nephrol. 2016 27 9 2861 2871 10.1681/ASN.2015070756 26823551
    [Google Scholar]
  34. Du H. Wang Q. Yang X. Fu brick tea alleviates chronic kidney disease of rats with high fat diet consumption through attenuating insulin resistance in skeletal muscle. J. Agric. Food Chem. 2019 67 10 2839 2847 10.1021/acs.jafc.8b06927 30829482
    [Google Scholar]
  35. Hall J.E. do Carmo J.M. da Silva A.A. Wang Z. Hall M.E. Obesity-Induced Hypertension. Circ. Res. 2015 116 6 991 1006 10.1161/CIRCRESAHA.116.305697 25767285
    [Google Scholar]
  36. Tain Y.L. Lin Y.J. Sheen J.M. Yu H.R. Tiao M.M. Chen C.C. Tsai C.C. Huang L.T. Hsu C.N. High fat diets sex-specifically affect the renal transcriptome and program obesity, kidney injury, and hypertension in the offspring. Nutrients 2017 9 4 357 10.3390/nu9040357 28368364
    [Google Scholar]
  37. Ohashi N. Ishigaki S. Isobe S. The pivotal role of melatonin in ameliorating chronic kidney disease by suppression of the renin–angiotensin system in the kidney. Hypertens. Res. 2019 42 6 761 768 10.1038/s41440‑018‑0186‑2 30610209
    [Google Scholar]
  38. Passos-Silva D.G. Brandan E. Santos R.A.S. Angiotensins as therapeutic targets beyond heart disease. Trends Pharmacol. Sci. 2015 36 5 310 320 10.1016/j.tips.2015.03.001 25847571
    [Google Scholar]
  39. Liao W.H. Suendermann C. Steuer A.E. Pacheco Lopez G. Odermatt A. Faresse N. Henneberg M. Langhans W. Aldosterone deficiency in mice burdens respiration and accentuates diet-induced hyperinsulinemia and obesity. JCI Insight 2018 3 14 e99015 10.1172/jci.insight.99015 30046010
    [Google Scholar]
  40. van Zonneveld A.J. Rabelink T.J. Mesangial cells defy LDL receptor paradigm. Kidney Int. 2001 60 5 2037 2038 10.1046/j.1523‑1755.2001.00023.x 11703627
    [Google Scholar]
  41. Li Z. Woollard J.R. Wang S. Korsmo M.J. Ebrahimi B. Grande J.P. Textor S.C. Lerman A. Lerman L.O. Increased glomerular filtration rate in early metabolic syndrome is associated with renal adiposity and microvascular proliferation. Am. J. Physiol. Renal Physiol. 2011 301 5 F1078 F1087 10.1152/ajprenal.00333.2011 21775485
    [Google Scholar]
  42. Nishi H. Higashihara T. Inagi R. Lipotoxicity in kidney, heart, and skeletal muscle dysfunction. Nutrients 2019 11 7 1664 10.3390/nu11071664 31330812
    [Google Scholar]
  43. Mount P. Davies M. Choy S.W. Cook N. Power D. Obesity-related chronic kidney disease—the role of lipid metabolism. Metabolites 2015 5 4 720 732 10.3390/metabo5040720 26690487
    [Google Scholar]
  44. Yang X. Okamura D.M. Lu X. Chen Y. Moorhead J. Varghese Z. Ruan X.Z. CD36 in chronic kidney disease: Novel insights and therapeutic opportunities. Nat. Rev. Nephrol. 2017 13 12 769 781 10.1038/nrneph.2017.126 28919632
    [Google Scholar]
  45. Opazo-Ríos L. Mas S. Marín-Royo G. Mezzano S. Gómez-Guerrero C. Moreno J.A. Egido J. Lipotoxicity and diabetic nephropathy: novel mechanistic insights and therapeutic opportunities. Int. J. Mol. Sci. 2020 21 7 2632 10.3390/ijms21072632 32290082
    [Google Scholar]
  46. Adeosun S.O. Gordon D.M. Weeks M.F. Moore K.H. Hall J.E. Hinds T.D. Jr Stec D.E. Loss of biliverdin reductase-A promotes lipid accumulation and lipotoxicity in mouse proximal tubule cells. Am. J. Physiol. Renal Physiol. 2018 315 2 F323 F331 10.1152/ajprenal.00495.2017 29631357
    [Google Scholar]
  47. Weinberg J.M. Lipotoxicity. Kidney Int. 2006 70 9 1560 1566 10.1038/sj.ki.5001834 16955100
    [Google Scholar]
  48. Katsoulieris E. Mabley J.G. Samai M. Sharpe M.A. Green I.C. Chatterjee P.K. Lipotoxicity in renal proximal tubular cells: Relationship between endoplasmic reticulum stress and oxidative stress pathways. Free Radic. Biol. Med. 2010 48 12 1654 1662 10.1016/j.freeradbiomed.2010.03.021 20363316
    [Google Scholar]
  49. Horton J.D. Shah N.A. Warrington J.A. Anderson N.N. Park S.W. Brown M.S. Goldstein J.L. Combined analysis of oligonucleotide microarray data from transgenic and knockout mice identifies direct SREBP target genes. Proc. Natl. Acad. Sci. USA 2003 100 21 12027 12032 10.1073/pnas.1534923100 14512514
    [Google Scholar]
  50. Tominaga T. Dutta R.K. Joladarashi D. Doi T. Reddy J.K. Kanwar Y.S. Transcriptional and translational modulation of myo-inositol oxygenase (Miox) by fatty acids: Implications in renal tubular injury induced in obesity and diabetes. J. Biol. Chem. 2016 291 3 1348 1367 10.1074/jbc.M115.698191 26578517
    [Google Scholar]
  51. Zhu Q. Scherer P.E. Immunologic and endocrine functions of adipose tissue: Implications for kidney disease. Nat. Rev. Nephrol. 2018 14 2 105 120 10.1038/nrneph.2017.157 29199276
    [Google Scholar]
  52. Chen Y. Varghese Z. Ruan X.Z. The molecular pathogenic role of inflammatory stress in dysregulation of lipid homeostasis and hepatic steatosis. Genes Dis. 2014 1 1 106 112 10.1016/j.gendis.2014.07.007 30258859
    [Google Scholar]
  53. Kang H.M. Ahn S.H. Choi P. Ko Y.A. Han S.H. Chinga F. Park A.S.D. Tao J. Sharma K. Pullman J. Bottinger E.P. Goldberg I.J. Susztak K. Defective fatty acid oxidation in renal tubular epithelial cells has a key role in kidney fibrosis development. Nat. Med. 2015 21 1 37 46 10.1038/nm.3762 25419705
    [Google Scholar]
  54. Yang P. Xiao Y. Luo X. Zhao Y. Zhao L. Wang Y. Wu T. Wei L. Chen Y. Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice. J. Lipid Res. 2017 58 7 1417 1427 10.1194/jlr.M076216 28536108
    [Google Scholar]
  55. Rosca M.G. Vazquez E.J. Chen Q. Kerner J. Kern T.S. Hoppel C.L. Oxidation of fatty acids is the source of increased mitochondrial reactive oxygen species production in kidney cortical tubules in early diabetes. Diabetes 2012 61 8 2074 2083 10.2337/db11‑1437 22586586
    [Google Scholar]
  56. Giacco F. Brownlee M. Oxidative stress and diabetic complications. Circ. Res. 2010 107 9 1058 1070 10.1161/CIRCRESAHA.110.223545 21030723
    [Google Scholar]
  57. Straznicky N.E. Grima M.T. Lambert E.A. Eikelis N. Dawood T. Lambert G.W. Nestel P.J. Masuo K. Sari C.I. Chopra R. Mariani J.A. Schlaich M.P. Exercise augments weight loss induced improvement in renal function in obese metabolic syndrome individuals. J. Hypertens. 2011 29 3 553 564 10.1097/HJH.0b013e3283418875 21119532
    [Google Scholar]
  58. Friedman A.N. Chambers M. Kamendulis L.M. Temmerman J. Short-term changes after a weight reduction intervention in advanced diabetic nephropathy. Clin. J. Am. Soc. Nephrol. 2013 8 11 1892 1898 10.2215/CJN.04010413 23929927
    [Google Scholar]
  59. Gong C. Kim Y.K. Woeller C.F. Tang Y. Maquat L.E. SMD and NMD are competitive pathways that contribute to myogenesis: effects on PAX3 and myogenin mRNAs. Genes Dev. 2009 23 1 54 66 10.1101/gad.1717309 19095803
    [Google Scholar]
  60. Kassem M.A.M. Durda M.A. Stoicea N. Cavus O. Sahin L. Rogers B. The impact of bariatric surgery on type 2 diabetes mellitus and the management of hypoglycemic events. Front. Endocrinol. (Lausanne) 2017 8 37 10.3389/fendo.2017.00037 28298900
    [Google Scholar]
  61. Ritz E. Bariatric surgery and the kidney—much benefit, but also potential harm. Clin. Kidney J. 2013 6 4 368 372 10.1093/ckj/sfs161 27293562
    [Google Scholar]
  62. Bellini M.I. Paoletti F. Herbert P.E. Obesity and bariatric intervention in patients with chronic renal disease. J. Int. Med. Res. 2019 47 6 2326 2341 10.1177/0300060519843755 31006298
    [Google Scholar]
  63. Weisinger J.R. Kempson R.L. Eldridge F.L. Swenson R.S. The nephrotic syndrome: a complication of massive obesity. Ann. Intern. Med. 1974 81 4 440 447 10.7326/0003‑4819‑81‑4‑440 4416380
    [Google Scholar]
  64. Chagnac A. Herman M. Zingerman B. Erman A. Rozen-Zvi B. Hirsh J. Gafter U. Obesity-induced glomerular hyperfiltration: Its involvement in the pathogenesis of tubular sodium reabsorption. Nephrol. Dial. Transplant. 2008 23 12 3946 3952 10.1093/ndt/gfn379 18622024
    [Google Scholar]
  65. Wuerzner G. Pruijm M. Maillard M. Bovet P. Renaud C. Burnier M. Bochud M. Marked association between obesity and glomerular hyperfiltration: A cross-sectional study in an African population. Am. J. Kidney Dis. 2010 56 2 303 312 10.1053/j.ajkd.2010.03.017 20538392
    [Google Scholar]
  66. Chagnac A. Weinstein T. Herman M. Hirsh J. Gafter U. Ori Y. The effects of weight loss on renal function in patients with severe obesity. J. Am. Soc. Nephrol. 2003 14 6 1480 1486 10.1097/01.ASN.0000068462.38661.89 12761248
    [Google Scholar]
  67. Chagnac A. Weinstein T. Korzets A. Ramadan E. Hirsch J. Gafter U. Glomerular hemodynamics in severe obesity. Am. J. Physiol. Renal Physiol. 2000 278 5 F817 F822 10.1152/ajprenal.2000.278.5.F817 10807594
    [Google Scholar]
  68. Hall J. Mechanisms of abnormal renal sodium handling in obesity hypertension. Am. J. Hypertens. 1997 10 12 49S 55S 10.1016/S0895‑7061(97)00075‑7 9160781
    [Google Scholar]
  69. Szeto H.H. Liu S. Soong Y. Alam N. Prusky G.T. Seshan S.V. Protection of mitochondria prevents high-fat diet–induced glomerulopathy and proximal tubular injury. Kidney Int. 2016 90 5 997 1011 10.1016/j.kint.2016.06.013 27519664
    [Google Scholar]
  70. 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 3 561 572 10.1194/jlr.P040501 24371263
    [Google Scholar]
  71. Chen H.M. Chen Y. Zhang Y.D. Zhang P.P. Chen H.P. Wang Q.W. Li L.S. Liu Z.H. Evaluation of metabolic risk marker in obesity-related glomerulopathy. J. Ren. Nutr. 2011 21 4 309 315 10.1053/j.jrn.2010.06.019 20833076
    [Google Scholar]
  72. Tsuboi N. Koike K. Hirano K. Utsunomiya Y. Kawamura T. Hosoya T. Clinical features and long-term renal outcomes of Japanese patients with obesity-related glomerulopathy. Clin. Exp. Nephrol. 2013 17 3 379 385 10.1007/s10157‑012‑0719‑y 23135866
    [Google Scholar]
  73. Pehlivan E. Ozen G. Taskapan H. Gunes G. Sahin I. Çolak C. Identifying the determinants of microalbuminuria in obese patients in primary care units: The effects of blood pressure, random plasma glucose and other risk factors. J. Endocrinol. Invest. 2016 39 1 73 82 10.1007/s40618‑015‑0331‑6 26093468
    [Google Scholar]
  74. Hashimoto Y. Tanaka M. Okada H. Senmaru T. Hamaguchi M. Asano M. Yamazaki M. Oda Y. Hasegawa G. Toda H. Nakamura N. Fukui M. Metabolically healthy obesity and risk of incident CKD. Clin. J. Am. Soc. Nephrol. 2015 10 4 578 583 10.2215/CJN.08980914 25635035
    [Google Scholar]
  75. WenYuan LW Lin Central obesity and albuminuria: Both cross- sectional and longitudinal studies in Chinese PLoS One. 2012 7 12 e47960
    [Google Scholar]
  76. Filler G. Lepage N. Should the Schwartz formula for estimation of GFR be replaced by cystatin C formula? Pediatr. Nephrol. 2003 18 10 981 985 10.1007/s00467‑003‑1271‑5 12920638
    [Google Scholar]
  77. Groesbeck D. Köttgen A. Parekh R. Selvin E. Schwartz G.J. Coresh J. Furth S. Age, gender, and race effects on cystatin C levels in US adolescents. Clin. J. Am. Soc. Nephrol. 2008 3 6 1777 1785 10.2215/CJN.00840208 18815241
    [Google Scholar]
  78. Hogg R.J. Portman R.J. Milliner D. Lemley K.V. Eddy A. Ingelfinger J. Evaluation and management of proteinuria and nephrotic syndrome in children: Recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics 2000 105 6 1242 1249 10.1542/peds.105.6.1242 10835064
    [Google Scholar]
  79. Abitbol C.L. Chandar J. Onder A.M. Nwobi O. Montané B. Zilleruelo G. Profiling proteinuria in pediatric patients. Pediatr. Nephrol. 2006 21 7 995 1002 10.1007/s00467‑006‑0103‑9 16773413
    [Google Scholar]
  80. Vejakama P. Ingsathit A. McKay G.J. Maxwell A.P. McEvoy M. Attia J. Thakkinstian A. Treatment effects of renin-angiotensin aldosterone system blockade on kidney failure and mortality in chronic kidney disease patients. BMC Nephrol. 2017 18 1 342 10.1186/s12882‑017‑0753‑9 29187194
    [Google Scholar]
  81. Tsuboi N. Utsunomiya Y. Kanzaki G. Koike K. Ikegami M. Kawamura T. Hosoya T. Low glomerular density with glomerulomegaly in obesity-related glomerulopathy. Clin. J. Am. Soc. Nephrol. 2012 7 5 735 741 10.2215/CJN.07270711 22403274
    [Google Scholar]
  82. Li H. Li M. Liu P. Wang Y. Zhang H. Li H. Yang S. Song Y. Yin Y. Gao L. Cheng S. Cai J. Tian G. Telmisartan ameliorates nephropathy in metabolic syndrome by reducing leptin release from perirenal adipose tissue. Hypertension 2016 68 2 478 490 10.1161/HYPERTENSIONAHA.116.07008 27296996
    [Google Scholar]
  83. Garg R. Adler G.K. Aldosterone and the mineralocorticoid receptor: risk factors for cardiometabolic disorders. Curr. Hypertens. Rep. 2015 17 7 52 10.1007/s11906‑015‑0567‑8 26068659
    [Google Scholar]
  84. Chamberlain J.J. Herman W.H. Leal S. Rhinehart A.S. Shubrook J.H. Skolnik N. Kalyani R.R. Pharmacologic therapy for type 2 diabetes: Synopsis of the 2017 american diabetes association standards of medical care in diabetes. Ann. Intern. Med. 2017 166 8 572 578 10.7326/M16‑2937 28288484
    [Google Scholar]
  85. Greco E. Russo G. Giandalia A. Viazzi F. Pontremoli R. De Cosmo S. GLP-1 receptor agonists and kidney protection. Medicina (Kaunas) 2019 55 6 233 10.3390/medicina55060233 31159279
    [Google Scholar]
  86. Bomback A.S. Muskala P. Bald E. Chwatko G. Nowicki M. Low- dose spironolactone, added to long-term ACE inhibitor therapy, reduces blood pressure and urinary albumin excretion in obese patients with hypertensive target organ damage. Clin. Nephrol. 2009 72 12 449 456 10.5414/CNP72449 19954722
    [Google Scholar]
  87. Jaikumkao K. Pongchaidecha A. Chatsudthipong V. Chattipakorn S.C. Chattipakorn N. Lungkaphin A. The roles of sodium-glucose cotransporter 2 inhibitors in preventing kidney injury in diabetes. Biomed. Pharmacother. 2017 94 176 187 10.1016/j.biopha.2017.07.095 28759755
    [Google Scholar]
  88. Vallon V. Thomson S.C. Targeting renal glucose reabsorption to treat hyperglycaemia: the pleiotropic effects of SGLT2 inhibition. Diabetologia 2017 60 2 215 225 10.1007/s00125‑016‑4157‑3 27878313
    [Google Scholar]
  89. Eleftheriadis T. Pissas G. Tsogka K. Nikolaou E. Liakopoulos V. Stefanidis I. A unifying model of glucotoxicity in human renal proximal tubular epithelial cells and the effect of the SGLT2 inhibitor dapagliflozin. Int. Urol. Nephrol. 2020 52 6 1179 1189 10.1007/s11255‑020‑02481‑3 32361978
    [Google Scholar]
  90. Wang X.X. Levi J. Luo Y. Myakala K. Herman-Edelstein M. Qiu L. Wang D. Peng Y. Grenz A. Lucia S. Dobrinskikh E. D’Agati V.D. Koepsell H. Kopp J.B. Rosenberg A.Z. Levi M. SGLT2 protein expression is increased in human diabetic nephropathy: SGLT2 protein inhibition decreases renal lipid accumulation, inflammation, and the development of nephropathy in diabetic mice. J. Biol. Chem. 2017 292 13 5335 5348 10.1074/jbc.M117.779520 28196866
    [Google Scholar]
  91. Dorotea D. Koya D. Ha H. Recent insights into SREBP as a direct mediator of kidney fibrosis via lipid-independent pathways. Front. Pharmacol. 2020 11 265 10.3389/fphar.2020.00265 32256356
    [Google Scholar]
  92. Han C. Update on FXR biology: promising therapeutic target? Int. J. Mol. Sci. 2018 19 7 2069 10.3390/ijms19072069 30013008
    [Google Scholar]
  93. Zhang Y. Ma K.L. Liu J. Wu Y. Hu Z.B. Liu L. Liu B.C. Dysregulation of low-density lipoprotein receptor contributes to podocyte injuries in diabetic nephropathy. Am. J. Physiol. Endocrinol. Metab. 2015 308 12 E1140 E1148 10.1152/ajpendo.00591.2014 25921580
    [Google Scholar]
  94. Asai H.T. Tanaka S. Uegima K. Linear regression analysis with fuzzy model. IEEE Trans. Syst. Man Cybern. 1982 12 6 903 907 10.1109/TSMC.1982.4308925
    [Google Scholar]
  95. Hong Y.A. Lim J.H. Kim M.Y. Kim T.W. Kim Y. Yang K.S. Park H.S. Choi S.R. Chung S. Kim H.W. Kim H.W. Choi B.S. Chang Y.S. Park C.W. Fenofibrate Improves Renal Lipotoxicity through Activation of AMPK-PGC-1α in db/db Mice. PLoS One 2014 9 5 e96147 10.1371/journal.pone.0096147 24801481
    [Google Scholar]
  96. Tsai H.C. Chang F.P. Li T.H. Liu C.W. Huang C.C. Huang S.F. Yang Y.Y. Lee K.C. Hsieh Y.C. Wang Y.W. Lee T.Y. Huang Y.H. Hou M.C. Lin H.C. Elafibranor inhibits chronic kidney disease progression in NASH mice. BioMed Res. Int. 2019 2019 1 14 10.1155/2019/6740616 31321239
    [Google Scholar]
  97. Kratzer A. Buchebner M. Pfeifer T. Becker T.M. Uray G. Miyazaki M. Miyazaki-Anzai S. Ebner B. Chandak P.G. Kadam R.S. Calayir E. Rathke N. Ahammer H. Radovic B. Trauner M. Hoefler G. Kompella U.B. Fauler G. Levi M. Levak-Frank S. Kostner G.M. Kratky D. Synthetic LXR agonist attenuates plaque formation in apoE-/- mice without inducing liver steatosis and hypertriglyceridemia. J. Lipid Res. 2009 50 2 312 326 10.1194/jlr.M800376‑JLR200 18812595
    [Google Scholar]
  98. Calkin A.C. Tontonoz P. Transcriptional integration of metabolism by the nuclear sterol-activated receptors LXR and FXR. Nat. Rev. Mol. Cell Biol. 2012 13 4 213 224 10.1038/nrm3312 22414897
    [Google Scholar]
  99. Wu J. Zhang Y. Wang N. Davis L. Yang G. Wang X. Zhu Y. Breyer M.D. Guan Y. Liver X receptor-α mediates cholesterol efflux in glomerular mesangial cells. Am. J. Physiol. Renal Physiol. 2004 287 5 F886 F895 10.1152/ajprenal.00123.2004 15280160
    [Google Scholar]
  100. Zhang H. Liu Y. Wang L. Li Z. Zhang H. Wu J. Rahman N. Guo Y. Li D. Li N. Huhtaniemi I. Tsang S.Y. Gao G.F. Li X. Differential effects of estrogen/androgen on the prevention of nonalcoholic fatty liver disease in the male rat. J. Lipid Res. 2013 54 2 345 357 10.1194/jlr.M028969 23175777
    [Google Scholar]
  101. Wang Y. Moser A.H. Shigenaga J.K. Grunfeld C. Feingold K.R. Downregulation of liver X receptor-α in mouse kidney and HK-2 proximal tubular cells by LPS and cytokines. J. Lipid Res. 2005 46 11 2377 2387 10.1194/jlr.M500134‑JLR200 16106051
    [Google Scholar]
  102. Tachibana H. Ogawa D. Matsushita Y. Bruemmer D. Wada J. Teshigawara S. Eguchi J. Sato-Horiguchi C. Uchida H.A. Shikata K. Makino H. Activation of liver X receptor inhibits osteopontin and ameliorates diabetic nephropathy. J. Am. Soc. Nephrol. 2012 23 11 1835 1846 10.1681/ASN.2012010022 23085633
    [Google Scholar]
  103. Morales E. Valero M. León M. Hernández E. Praga M. Beneficial effects of weight loss in overweight patients with chronic proteinuric nephropathies. Am. J. Kidney Dis. 2003 41 2 319 327 10.1053/ajkd.2003.50039 12552492
    [Google Scholar]
  104. Afshinnia F. Wilt T.J. Duval S. Esmaeili A. Ibrahim H.N. Weight loss and proteinuria: Systematic review of clinical trials and comparative cohorts. Nephrol. Dial. Transplant. 2010 25 4 1173 1183 10.1093/ndt/gfp640 19945950
    [Google Scholar]
  105. Navaneethan S.D. Yehnert H. Moustarah F. Schreiber M.J. Schauer P.R. Beddhu S. Weight loss interventions in chronic kidney disease: a systematic review and meta-analysis. Clin. J. Am. Soc. Nephrol. 2009 4 10 1565 1574 10.2215/CJN.02250409 19808241
    [Google Scholar]
  106. Raj Krishnamurthy V.M. Wei G. Baird B.C. Murtaugh M. Chonchol M.B. Raphael K.L. Greene T. Beddhu S. High dietary fiber intake is associated with decreased inflammation and all- cause mortality in patients with chronic kidney disease. Kidney Int. 2012 81 3 300 306 10.1038/ki.2011.355 22012132
    [Google Scholar]
  107. Vaziri N.D. Liu S.M. Lau W.L. Khazaeli M. Nazertehrani S. Farzaneh S.H. Kieffer D.A. Adams S.H. Martin R.J. High amylose resistant starch diet ameliorates oxidative stress, inflammation, and progression of chronic kidney disease. PLoS One 2014 9 12 e114881 10.1371/journal.pone.0114881 25490712
    [Google Scholar]
  108. DeBoer M.D. Filipp S.L. Musani S.K. Sims M. Okusa M.D. Gurka M. Metabolic syndrome severity and risk of CKD and worsened GFR: The Jackson Heart Study. Kidney Blood Press. Res. 2018 43 2 555 567 10.1159/000488829 29642060
    [Google Scholar]
  109. Taubes G. Treat obesity as physiology, not physics. Nature 2012 492 7428 155 10.1038/492155a 23235840
    [Google Scholar]
  110. Friedman A.N. The case for a bariatric-centered approach to CKD care. Clin. J. Am. Soc. Nephrol. 2019 14 2 291 293 10.2215/CJN.12061018 30630858
    [Google Scholar]
  111. Nehus E.J. Khoury J.C. Inge T.H. Xiao N. Jenkins T.M. Moxey-Mims M.M. Mitsnefes M.M. Kidney outcomes three years after bariatric surgery in severely obese adolescents. Kidney Int. 2017 91 2 451 458 10.1016/j.kint.2016.09.031 27914704
    [Google Scholar]
  112. La Russa D. Giordano F. Marrone A. Parafati M. Janda E. Pellegrino D. Oxidative imbalance and kidney damage in cafeteria diet-induced rat model of metabolic syndrome: Effect of bergamot polyphenolic fraction. Antioxidants 2019 8 3 66 10.3390/antiox8030066 30884780
    [Google Scholar]
  113. Kambham N. Markowitz G.S. Valeri A.M. Lin J. D’Agati V.D. Obesity-related glomerulopathy: An emerging epidemic. Kidney Int. 2001 59 4 1498 1509 10.1046/j.1523‑1755.2001.0590041498.x 11260414
    [Google Scholar]
  114. Praga M. Hernández E. Morales E. Campos A.P. Valero M.A. Martínez M.A. León M. Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis. Nephrol. Dial. Transplant. 2001 16 9 1790 1798 10.1093/ndt/16.9.1790 11522860
    [Google Scholar]
  115. Tsuboi N. Okabayashi Y. Shimizu A. Yokoo T. The renal pathology of obesity. Kidney Int. Rep. 2017 2 2 251 260 10.1016/j.ekir.2017.01.007 29142961
    [Google Scholar]
  116. Murlidharan P Kamaladevan S Balan S Kartha CC Mechanisms for obesity related kidney disease. Pathophysiology of Obesity-Induced Health Complications 2020 Springer, Cham Zug, Switzerland 19 193 216 10.1007/978‑3‑030‑35358‑2_12
    [Google Scholar]
  117. Stasi A. Cosola C. Caggiano G. Cimmarusti M.T. Palieri R. Acquaviva P.M. Rana G. Gesualdo L. Obesity-related chronic kidney disease: Principal mechanisms and new approaches in nutritional management. Front. Nutr. 2022 9 925619 10.3389/fnut.2022.925619 35811945
    [Google Scholar]
  118. Hao M. Lv Y. Liu S. Guo W. The new challenge of obesity - obesity-associated nephropathy. Diabetes Metab. Syndr. Obes. 2024 17 1957 1971 10.2147/DMSO.S433649 38737387
    [Google Scholar]
/content/journals/cdt/10.2174/0113894501314788241008115712
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Molecular Insight into Obesity-Associated Nephropathy: Clinical Implications and Possible Strategies for its Management
Bentham Science Publishers ; https://doi.org/10.2174/0113894501314788241008115712
/content/journals/cdt/10.2174/0113894501314788241008115712
/content/journals/cdt/10.2174/0113894501314788241008115712
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  • Article Type:     Review Article
Keywords: lipid metabolism ; insulin resistance ; Obesity ; inflammation ; chronic kidney disease

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