Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment

doi:10.1007/s11684-017-0570-3

Frontiers of Medicine

2017, Vol. 11

Issue (3): 340-348 https://doi.org/10.1007/s11684-017-0570-3

本期目录

Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment

Tianhua Xu, Zitong Sheng, Li Yao(

)

Department of Nephrology, The First Hospital of China Medical University, Shenyang 110001, China

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Abstract：

In light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related glomerulopathy (ORG) is characterized by glomerulomegaly in the presence or absence of focal and segmental glomerulosclerosis lesions. IgM and complement 3 (C3) nonspecifically deposit in lesions without immune-complex-type deposits during ORG immunofluorescence. ORG-associated glomerulomegaly and focal and segmental glomerulosclerosis can superimpose on other renal pathologies. The mechanisms under ORG are complex, especially hemodynamic changes, inflammation, oxidative stress, apoptosis, and reduced functioning nephrons. These mechanisms synergize with obesity to induce end-stage renal disease. A slow increase of subnephrotic proteinuria (<3.5 g/d) is the most common clinical manifestation of ORG. Several treatment methods for ORG have been developed. Of these methods, renin–angiotensin–aldosterone system blockade and weight loss are proven effective. Targeting mitochondria may offer a novel strategy for ORG therapy. Nevertheless, more research is needed to further understand ORG.

Key words： obesity-related glomerulopathy pathogenesis pathologic clinical characteristics

收稿日期: 2017-01-14 出版日期: 2017-08-29

Corresponding Author(s): Li Yao

引用本文:

. [J]. Frontiers of Medicine, 2017, 11(3): 340-348.
Tianhua Xu, Zitong Sheng, Li Yao. Obesity-related glomerulopathy: pathogenesis, pathologic, clinical characteristics and treatment. Front. Med., 2017, 11(3): 340-348.

链接本文:

https://academic.hep.com.cn/fmd/CN/10.1007/s11684-017-0570-3
https://academic.hep.com.cn/fmd/CN/Y2017/V11/I3/340

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Tab.1

1	Jia W. Obesity in China: its characteristics, diagnostic criteria, and implications. Front Med 2015; 9(2): 129–133 https://doi.org/10.1007/s11684-015-0387-x pmid: 25620117
2	Kambham N, Markowitz GS, Valeri AM , Lin J, D’Agati VD. Obesity-related glomerulopathy: an emerging epidemic. Kidney Int 2001; 59(4): 1498–1509 https://doi.org/10.1046/j.1523-1755.2001.0590041498.x pmid: 11260414
3	D’Agati VD, Chagnac A, de Vries AP , Levi M, Porrini E, Herman-Edelstein M , Praga M . Obesity-related glomerulopathy: clinical and pathologic characteristics and pathogenesis. Nat Rev Nephrol 2016; 12(8): 453–471 pmid: 27263398
4	D’Agati VD, Kaskel FJ, Falk RJ . Focal segmental glomerulosclerosis. N Engl J Med 2011; 365(25): 2398–2411 https://doi.org/10.1056/NEJMra1106556 pmid: 22187987
5	Serra A, Romero R, Lopez D , Navarro M , Esteve A , Perez N , Alastrue A , Ariza A . Renal injury in the extremely obese patients with normal renal function. Kidney Int 2008; 73(8): 947–955 https://doi.org/10.1038/nrneph.2016.75 pmid: 18216780
6	Hughson MD, Hoy WE, Douglas-Denton RN , Zimanyi MA , Bertram JF . Towards a definition of glomerulomegaly: clinical-pathological and methodological considerations. Nephrol Dial Transplant 2011; 26(7): 2202–2208 https://doi.org/10.1093/ndt/gfq688 pmid: 21115671
7	de Vries AP, Ruggenenti P, Ruan XZ , Praga M , Cruzado JM , Bajema IM , D’Agati VD , Lamb HJ , Pongrac Barlovic D , Hojs R, Abbate M, Rodriquez R , Mogensen CE , Porrini E; ERA-EDTA Working Group Diabesity.Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease. Lancet Diabetes Endocrinol 2014; 2(5): 417–426 https://doi.org/10.1016/S2213-8587(14)70065-8 pmid: 24795255
8	Praga M, Morales E. The fatty kidney: obesity and renal disease. Nephron 2016 Jul 15. [Epub ahead of print] doi:10.1159/000447674 https://doi.org/10.1159/000447674 pmid: 27414023
9	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 pmid: 10807594
10	Fukuda A, Chowdhury MA, Venkatareddy MP , Wang SQ , Nishizono R , Suzuki T , Wickman LT , Wiggins JE , Muchayi T , Fingar D , Shedden KA , Inoki K , Wiggins RC . Growth-dependent podocyte failure causes glomerulosclerosis. J Am Soc Nephrol 2012; 23(8): 1351–1363 https://doi.org/10.1681/ASN.2012030271 pmid: 22773827
11	Liu Y. New insights into epithelial-mesenchymal transition in kidney fibrosis. J Am Soc Nephrol 2010; 21(2): 212–222 https://doi.org/10.1681/ASN.2008121226 pmid: 20019167
12	Matsusaka T, Sandgren E, Shintani A , Kon V, Pastan I, Fogo AB , Ichikawa I . Podocyte injury damages other podocytes. J Am Soc Nephrol 2011; 22(7): 1275–1285 https://doi.org/10.1681/ASN.2010090963 pmid: 21719786
13	Bobulescu IA, Lotan Y, Zhang J , Rosenthal TR , Rogers JT , Adams-Huet B , Sakhaee K , Moe OW. Triglycerides in the human kidney cortex: relationship with body size. PLoS One 2014; 9(8): e101285. doi: 10.1371 /journal.pone.0101285 https://doi.org/10.1371 /journal.pone.0101285
14	Stefan N, Artunc F, Heyne N , Machann J , Schleicher ED , Häring HU . Obesity and renal disease: not all fat is created equal and not all obesity is harmful to the kidneys. Nephrol Dial Transplant 2016; 31(5): 726–730 https://doi.org/10.1093/ndt/gfu081 pmid: 24753460
15	Wu Y, Liu Z, Xiang Z , Zeng C, Chen Z, Ma X , Li L. Obesity-related glomerulopathy: insights from gene expression profiles of the glomeruli derived from renal biopsy samples. Endocrinology 2006; 147(1): 44–50 https://doi.org/10.1210/en.2005-0641 pmid: 16210374
16	Bonnet F, Deprele C, Sassolas A , Moulin P , Alamartine E , Berthezène F , Berthoux F . Excessive body weight as a new independent risk factor for clinical and pathological progression in primary IgA nephritis. Am J Kidney Dis 2001; 37(4): 720–727 https://doi.org/10.1016/S0272-6386(01)80120-7 pmid: 11273871
17	D’Agati VD, Markowitz GS. Supersized kidneys: lessons from the preclinical obese kidney. Kidney Int 2008; 73(8): 909–910 https://doi.org/10.1038/ki.2008.42 pmid: 18379527
18	Felizardo RJ, da Silva MB, Aguiar CF , Câmara NO . Obesity in kidney disease: a heavyweight opponent. World J Nephrol 2014; 3(3): 50–63 https://doi.org/10.5527/wjn.v3.i3.50 pmid: 25332896
19	Weisinger JR, Kempson RL, Eldridge FL , Swenson RS . The nephrotic syndrome: a complication of massive obesity. Ann Intern Med 1974; 81(4): 440–447 https://doi.org/10.7326/0003-4819-81-4-440 pmid: 4416380
20	Kriz W, Lemley KV. A potential role for mechanical forces in the detachment of podocytes and the progression of CKD. J Am Soc Nephrol 2015; 26(2): 258–269 https://doi.org/10.1681/ASN.2014030278 pmid: 25060060
21	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 https://doi.org/10.1053/j.ajkd.2010.03.017 pmid: 20538392
22	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 https://doi.org/10.1097/01.ASN.0000068462.38661.89 pmid: 12761248
23	Novikov A, Vallon V. Sodium glucose cotransporter 2 inhibition in the diabetic kidney: an update. Curr Opin Nephrol Hypertens 2016; 25(1): 50–58 https://doi.org/10.1097/MNH.0000000000000187 pmid: 26575393
24	Zinman B, Wanner C, Lachin JM , Fitchett D , Bluhmki E , Hantel S , Mattheus M , Devins T , Johansen OE , Woerle HJ , Broedl UC , Inzucchi SE; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22): 2117–2128 https://doi.org/10.1056/NEJMoa1504720 pmid: 26378978
25	Zingerman B, Herman-Edelstein M, Erman A , Bar Sheshet Itach S , Ori Y, Rozen-Zvi B, Gafter U , Chagnac A . Effect of acetazolamide on obesity-induced glomerular hyperfiltration: a randomized controlled trial. PLoS One 2015; 10(9): e0137163 https://doi.org/10.1371/journal.pone.0137163 pmid: 26367377
26	Nishiyama A, Abe Y. Molecular mechanisms and therapeutic strategies of chronic renal injury: renoprotective effects of aldosterone blockade. J Pharmacol Sci 2006; 100(1): 9–16 https://doi.org/10.1254/jphs.FMJ05003X3 pmid: 16397374
27	Ribstein J, Du Cailar G, Fesler P , Mimran A . Relative glomerular hyperfiltration in primary aldosteronism. J Am Soc Nephrol 2005; 16(5): 1320–1325 https://doi.org/10.1681/ASN.2004100878 pmid: 15800124
28	Kawarazaki W, Nagase M, Yoshida S , Takeuchi M , Ishizawa K , Ayuzawa N , Ueda K, Fujita T. Angiotensin II- and salt-induced kidney injury through Rac1-mediated mineralocorticoid receptor activation. J Am Soc Nephrol 2012; 23(6): 997–1007 https://doi.org/10.1681/ASN.2011070734 pmid: 22440899
29	De Cosmo S, Menzaghi C, Prudente S , Trischitta V . Role of insulin resistance in kidney dysfunction: insights into the mechanism and epidemiological evidence. Nephrol Dial Transplant 2013; 28(1): 29–36 https://doi.org/10.1093/ndt/gfs290 pmid: 23048172
30	Chen S, Chen Y, Liu X , Li M, Wu B, Li Y , Liang Y , Shao X, Holthöfer H, Zou H . Association of insulin resistance with chronic kidney disease in non-diabetic subjects with normal weight. PLoS One 2013; 8(9): e74058.doi: 10.1371/journal.pone.0074058 https://doi.org/10.1371/journal.pone.0074058
31	Redon J, Lurbe E. The kidney in obesity. Curr Hypertens Rep 2015; 17(6): 555 https://doi.org/10.1007/s11906-015-0555-z pmid: 25893477
32	Ye J. Mechanisms of insulin resistance in obesity. Front Med 2013; 7(1): 14–24 https://doi.org/10.1007/s11684-013-0262-6 pmid: 23471659
33	Szeto HH, Liu S, Soong Y , Alam N, Prusky GT, Seshan SV . Protection of mitochondria prevents high-fat diet-induced glomerulopathy and proximal tubular injury. Kidney Int 2016; 90(5): 997–1011 https://doi.org/10.1016/j.kint.2016.06.013 pmid: 27519664
34	Tang C, Cai J, Dong Z . Mitochondrial dysfunction in obesity-related kidney disease: a novel therapeutic target. Kidney Int 2016; 90(5): 930–933 https://doi.org/10.1016/j.kint.2016.07.045 pmid: 27742195
35	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 https://doi.org/10.1194/jlr.P040501 pmid: 24371263
36	Sharma K. Obesity, oxidative stress, and fibrosis in chronic kidney disease. Kidney Int Suppl (2011) 2014; 4(1): 113–117 https://doi.org/10.1038/kisup.2014.21 pmid: 25401040
37	Declèves AE , Zolkipli Z , Satriano J , Wang L, Nakayama T, Rogac M , Le TP, Nortier JL, Farquhar MG , Naviaux RK , Sharma K . Regulation of lipid accumulation by AMP-activated kinase [corrected] in high fat diet-induced kidney injury. Kidney Int 2014; 85(3): 611–623 https://doi.org/10.1038/ki.2013.462 pmid: 24304883
38	Dugan LL, You YH, Ali SS , Diamond-Stanic M , Miyamoto S , DeCleves AE , Andreyev A , Quach T , Ly S, Shekhtman G, Nguyen W , Chepetan A , Le TP, Wang L, Xu M , Paik KP , Fogo A, Viollet B, Murphy A , Brosius F , Naviaux RK , Sharma K . AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest 2013; 123(11): 4888–4899 https://doi.org/10.1172/JCI66218 pmid: 24135141
39	Manabe I. Chronic inflammation links cardiovascular, metabolic and renal diseases. Circ J 2011; 75(12): 2739–2748 https://doi.org/10.1253/circj.CJ-11-1184 pmid: 22067929
40	Nolan E, O’Meara YM, Godson C . Lipid mediators of inflammation in obesity-related glomerulopathy. Nephrol Dial Transplant 2013; 28(4 Suppl 4): iv22–iv29 pmid: 24081855
41	Young CN, Morgan DA, Butler SD , Mark AL , Davisson RL . The brain subfornical organ mediates leptin-induced increases in renal sympathetic activity but not its metabolic effects. Hypertension 2013; 61(3): 737–744 https://doi.org/10.1161/HYPERTENSIONAHA.111.00405 pmid: 23357182
42	Nasrallah MP, Ziyadeh FN. Overview of the physiology and pathophysiology of leptin with special emphasis on its role in the kidney. Semin Nephrol 2013; 33(1): 54–65 https://doi.org/10.1016/j.semnephrol.2012.12.005 pmid: 23374894
43	Rutkowski JM, Wang ZV, Park AS , Zhang J , Zhang D , Hu MC, Moe OW, Susztak K , Scherer PE . Adiponectin promotes functional recovery after podocyte ablation. J Am Soc Nephrol 2013; 24(2): 268–282 https://doi.org/10.1681/ASN.2012040414 pmid: 23334396
44	Simonds SE, Pryor JT, Ravussin E , Greenway FL , Dileone R , Allen AM , Bassi J , Elmquist JK , Keogh JM , Henning E , Myers MG Jr, Licinio J , Brown RD , Enriori PJ , O’Rahilly S , Sternson SM , Grove KL , Spanswick DC , Farooqi IS , Cowley MA . Leptin mediates the increase in blood pressure associated with obesity. Cell 2014; 159(6): 1404–1416 https://doi.org/10.1016/j.cell.2014.10.058 pmid: 25480301
45	Ogna A, Forni Ogna V, Bochud M , Guessous I , Paccaud F , Burnier M , Wuerzner G . Association between obesity and glomerular hyperfiltration: the confounding effect of smoking and sodium and protein intakes. Eur J Nutr 2016; 55(3): 1089–1097 https://doi.org/10.1007/s00394-015-0923-0 pmid: 25971845
46	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 https://doi.org/10.2215/CJN.07270711 pmid: 22403274
47	Praga M, Hernández E, Morales E , Campos AP , Valero MA , Martínez MA , León M . Clinical features and long-term outcome of obesity-associated focal segmental glomerulosclerosis. Nephrol Dial Transplant 2001; 16(9): 1790–1798 https://doi.org/10.1093/ndt/16.9.1790 pmid: 11522860
48	Chen HM, Chen Y, Zhang YD , Zhang PP , Chen HP , Wang QW , Li LS, Liu ZH. Evaluation of metabolic risk marker in obesity-related glomerulopathy. J Ren Nutr 2011; 21(4): 309–315 https://doi.org/10.1053/j.jrn.2010.06.019 pmid: 20833076
49	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 https://doi.org/10.1007/s10157-012-0719-y pmid: 23135866
50	Praga M, Borstein B, Andres A , Arenas J , Oliet A , Montoyo C , Ruilope LM , Rodicio JL . Nephrotic proteinuria without hypoalbuminemia: clinical characteristics and response to angiotensin-converting enzyme inhibition. Am J Kidney Dis 1991; 17(3): 330–338 https://doi.org/10.1016/S0272-6386(12)80483-5 pmid: 1996578
51	Praga M, Morales E, Herrero JC , Pérez Campos A , Domínguez-Gil B , Alegre R , Vara J, Martínez MA. Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. Am J Kidney Dis 1999; 33(1): 52–58 https://doi.org/10.1016/S0272-6386(99)70257-X pmid: 9915267
52	Sethi S, Zand L, Nasr SH , Glassock RJ , Fervenza FC . Focal and segmental glomerulosclerosis: clinical and kidney biopsy correlations. Clin Kidney J 2014; 7(6): 531–537 https://doi.org/10.1093/ckj/sfu100 pmid: 25503953
53	Sethi S, Glassock RJ, Fervenza FC . Focal segmental glomerulosclerosis: towards a better understanding for the practicing nephrologist. Nephrol Dial Transplant 2015; 30(3): 375–384 https://doi.org/10.1093/ndt/gfu035 pmid: 24589721
54	Salvatore SP, Chevalier JM, Kuo SF , Audia PF , Seshan SV . Kidney disease in patients with obesity: It is not always obesity-related glomerulopathy alone. Obes Res Clin Pract2017 Apr 22. [Epub ahead of print] doi: 10.1016/j.orcp.2017.04.003 https://doi.org/10.1016/j.orcp.2017.04.003 pmid: 28442280
55	Saiki A, Nagayama D, Ohhira M , Endoh K , Ohtsuka M , Koide N , Oyama T , Miyashita Y , Shirai K . Effect of weight loss using formula diet on renal function in obese patients with diabetic nephropathy. Int J Obes 2005; 29(9): 1115–1120 https://doi.org/10.1038/sj.ijo.0803009 pmid: 15925953
56	Bolignano D, Zoccali C. Effects of weight loss on renal function in obese CKD patients: a systematic review. Nephrol Dial Transplant 2013; 28(Suppl 4): iv82–iv98 https://doi.org/10.1093/ndt/gft302 pmid: 24092846
57	Friedman AN, Chambers M, Kamendulis LM , Temmerman J . Short-term changes after a weight reduction intervention in advanced diabetic nephropathy. Clin J Am Soc Nephrol 2013; 8(11): 1892–1898 https://doi.org/10.2215/CJN.04010413 pmid: 23929927
58	Morales E, Valero MA, 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 https://doi.org/10.1053/ajkd.2003.50039 pmid: 12552492
59	Afshinnia F, Wilt TJ, Duval S , Esmaeili A , Ibrahim HN . Weight loss and proteinuria: systematic review of clinical trials and comparative cohorts. Nephrol Dial Transplant 2010; 25(4): 1173–1183 https://doi.org/10.1093/ndt/gfp640 pmid: 19945950
60	Serra A, Esteve A, Navarro-Díaz M, López D , Bancu I , Romero R . Long-term normal renal function after drastic weight reduction in patients with obesity-related glomerulopathy. Obes Facts 2015; 8(3): 188–199 https://doi.org/10.1159/000431027 pmid: 25968610
61	Schauer PR, Bhatt DL, Kirwan JP , Wolski K , Brethauer SA , Navaneethan SD , Aminian A , Pothier CE , Kim ES, Nissen SE, Kashyap SR; STAMPEDE Investigators. Bariatric surgery versus intensive medical therapy for diabetes—3-year outcomes. N Engl J Med 2014; 370(21): 2002–2013 https://doi.org/10.1056/NEJMoa1401329 pmid: 24679060
62	MacLaughlin HL, Hall WL, Patel AG , M acdougall IC . Laparoscopic sleeve gastrectomy is a novel and effective treatment for obesity in patients with chronic kidney disease. Obes Surg 2012; 22(1): 119–123 https://doi.org/10.1007/s11695-011-0448-4 pmid: 21611875
63	Neff KJ, Frankel AH, Tam FW , Sadlier DM , Godson C , le Roux CW . The effect of bariatric surgery on renal function and disease: a focus on outcomes and inflammation. Nephrol Dial Transplant 2013; 28(Suppl 4): iv73–iv82 https://doi.org/10.1093/ndt/gft262 pmid: 24071659
64	Reid TJ, Saeed S, McCoy S , Osewa AA , Persaud A , Ahmed L . The effect of bariatric surgery on renal function. Surg Obes Relat Dis 2014; 10(5): 808–813 https://doi.org/10.1016/j.soard.2014.02.048 pmid: 25304831
65	Saleh F, Kim SJ, Okrainec A , Jackson TD . Bariatric surgery in patients with reduced kidney function: an analysis of short-term outcomes. Surg Obes Relat Dis 2015; 11(4): 828–835 https://doi.org/10.1016/j.soard.2014.11.012 pmid: 25868831
66	Lieske JC, Mehta RA, Milliner DS , Rule AD , Bergstralh EJ , Sarr MG . Kidney stones are common after bariatric surgery. Kidney Int 2015; 87(4): 839–845 https://doi.org/10.1038/ki.2014.352 pmid: 25354237
67	Mallamaci F, Ruggenenti P, Perna A , Leonardis D , Tripepi R , Tripepi G , Remuzzi G , Zoccali C; REIN Study Group . ACE inhibition is renoprotective among obese patients with proteinuria. J Am Soc Nephrol 2011; 22(6): 1122–1128 https://doi.org/10.1681/ASN.2010090969 pmid: 21527660
68	Patil MR, Mishra A, Jain N , Gutch M , Tewari R . Weight loss for reduction of proteinuria in diabetic nephropathy: comparison with angiotensin-converting enzyme inhibitor therapy. Indian J Nephrol 2013; 23(2): 108–113 https://doi.org/10.4103/0971-4065.109412 pmid: 23716916
69	Miyazaki Y, Cersosimo E, Triplitt C , DeFronzo RA . Rosiglitazone decreases albuminuria in type 2 diabetic patients. Kidney Int 2007; 72(11): 1367–1373 https://doi.org/10.1038/sj.ki.5002516 pmid: 17805239
70	Zhang SQ, Sun YT, Xu TH , Zhang XF , Liu YZ, Ma MJ, Wang LN , Yao L. Protective effect of metformin on renal injury of C57BL/6J mouse treated with high fat diet. Pharmazie 2014; 69(12): 904–908 pmid: 25951664
71	Birk AV, Chao WM, Bracken C , Warren JD , Szeto HH . Targeting mitochondrial cardiolipin and the cytochrome c/cardiolipin complex to promote electron transport and optimize mitochondrial ATP synthesis. Br J Pharmacol 2014; 171(8): 2017–2028 https://doi.org/10.1111/bph.12468 pmid: 24134698
72	Pierine DT, Navarro ME, Minatel IO , Luvizotto RA , Nascimento AF , Ferreira AL , Yeum KJ , Corrêa CR . Lycopene supplementation reduces TNF- a via RAGE in the kidney of obese rats. Nutr Diabetes 2014; 4(11): e142 https://doi.org/10.1038/nutd.2014.39 pmid: 25383746
73	Stacchiotti A, Favero G, Giugno L , Lavazza A , Reiter RJ , Rodella LF , Rezzani R . Mitochondrial and metabolic dysfunction in renal convoluted tubules of obese mice: protective role of melatonin. PLoS One 2014; 9(10): e111141. DOI:10.1371/journal. pone. 0111141
74	Wang C, Wu M, Arvapalli R , Dai X, Mahmood M, Driscoll H , Rice KM , Blough E . Acetaminophen attenuates obesity-related renal injury through ER-mediated stress mechanisms. Cell Physiol Biochem 2014; 33(4): 1139–1148 https://doi.org/10.1159/000358683 pmid: 24731963

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