Kidney Adaptations Prevent Loss of Trace Elements in Wistar Rats with Early Metabolic Syndrome


Metabolic syndrome (MetS) represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance. These metabolic derangements present significant risk factors for chronic kidney disease that carries to loss of essential micronutrients, which accelerates comorbidity apparition. The work aimed was to evaluate the trace element homeostasis regarding morphological adaptations and renal function in MetS early-onset. Fifty male Wistar rats were divided into two groups: (a) control group and (b) hypercaloric diet group that developed MetS early-onset after 3 months. Classical zoometric parameters do not show changes; however, biochemical modifications were observed such as hyperglycemia, protein glycation, insulin resistance, dyslipidemia, hyperinsulinemia, and hypoadiponectinemia. MetS early-onset group observed renal structural modifications, but no functional changes. The structural modifications observed were minimal glomerular injury, glomerular basement membrane thickening, as well as mesangial and tubular cells that showed growth and proliferation. In serum and kidney (cortex and medulla), the concentrations of Zn, Fe, Cr, Mg, Mn, Cu, Co, and Ni were no differences between the experimental groups, but excretory fractions of these were lower in the hypercaloric diet group. In conclusion, MetS early-onset coexist renal structural modification and a hyperreabsorptive activity of essential trace elements that avoid its loss; thus, the excretory fraction of oligo-elements could be used a biomarker of early renal injury caused by metabolic diseases in the clinical practice.

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  1. 1.

    Alberti KGMM, Zimmet P, Shaw J (2005) The metabolic syndrome - a new worldwide definition. Lancet 366:1059–1062

    Article  Google Scholar 

  2. 2.

    Cleeman JI (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). J Am Med Assoc 285:2486–2497.

    Article  Google Scholar 

  3. 3.

    Simmons RK, Alberti KGMM, Gale EAM, Colagiuri S, Tuomilehto J, Qiao Q, Ramachandran A, Tajima N, Brajkovich Mirchov I, Ben-Nakhi A, Reaven G, Hama Sambo B, Mendis S, Roglic G (2010) The metabolic syndrome: useful concept or clinical tool? Report of a WHO expert consultation. Diabetologia 53:600–605

    CAS  Article  Google Scholar 

  4. 4.

    Alberti KGMM, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr, International Diabetes Federation Task Force on Epidemiology and Prevention, Hational Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, International Association for the Study of Obesity (2009) Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; national heart, lung, and blood institute; American heart association; world heart federation; international atherosclerosis society; and international association for the study of obesity. Circulation 120:1640–1645

    CAS  Article  Google Scholar 

  5. 5.

    Rosyid FN (2017) Issue 10 Page 4206 International Journal of Research in Medical Sciences Rosyid FN. Int J Res Med Sci 5:4206–4213.

  6. 6.

    Vaquero Alvarez M, Aparicio-Martinez P, Fonseca Pozo FJ, Valle Alonso J, Blancas Sánchez IM, Romero-Saldaña M (2020) A sustainable approach to the metabolic syndrome in children and its economic burden. Int J Environ Res Public Health 17:1891.

    Article  PubMed Central  Google Scholar 

  7. 7.

    Heiss G, Snyder ML, Teng Y, Schneiderman N, Llabre MM, Cowie C, Carnethon M, Kaplan R, Giachello A, Gallo L, Loehr L, Avilés-Santa L (2014) Prevalence of metabolic syndrome among hispanics/latinos of diverse background: the Hispanic community health study/study of Latinos. Diabetes Care 37:2391–2399.

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Nichols GA, Moler EJ (2011) Metabolic syndrome components are associated with future medical costs independent of cardiovascular hospitalization and incident diabetes. Metab Syndr Relat Disord 9:127–133.

    Article  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Curtis LH, Hammill BG, Bethel MA, Anstrom KJ, Gottdiener JS, Schulman KA (2007) Costs of the metabolic syndrome in elderly individuals: findings from the cardiovascular health study. Diabetes Care 30:2553–2558.

    Article  PubMed  Google Scholar 

  10. 10.

    Ohashi Y, Thomas G, Nurko S, Stephany B, Fatica R, Chiesa A, Rule AD, Srinivas T, Schold JD, Navaneethan SD, Poggio ED (2013) Association of metabolic syndrome with kidney function and histology in living kidney donors. Am J Transplant 13:2342–2351.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Szczuko M, Kaczkan M, Drozd A, Maciejewska D, Palma J, Owczarzak A, Marczuk N, Rutkowski P, Małgorzewicz S (2019) Comparison of fatty acid profiles in a group of female patients with chronic kidney diseases (CKD) and metabolic syndrome (MetS)similar trends of changes, Different Pathophysiology. Int J Mol Sci 20.

  12. 12.

    Litwin M, Niemirska A (2014) Metabolic syndrome in children with chronic kidney disease and after renal transplantation. Pediatr Nephrol 29:203–216

    Article  Google Scholar 

  13. 13.

    Thethi T, Kamiyama M, Kobori H (2012) The link between the renin-angiotensin-aldosterone system and renal injury in obesity and the metabolic syndrome. Curr Hypertens Rep 14:160–169.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Lin JW, Chang YC, Li HY, Chien YF, Wu MY, Tsai RY, Hsieh YC, Chen YJ, Hwang JJ, Chuang LM (2009) Cross-sectional validation of diabetes risk scores for predicting diabetes, metabolic syndrome, and chronic kidney disease in Taiwanese. Diabetes Care 32:2294–2296.

    Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    Siddiqui K, Bawazeer N, Joy SS (2014) Variation in macro and trace elements in progression of type 2 diabetes. Sci World J 2014:1–9.

    CAS  Article  Google Scholar 

  16. 16.

    Matsumura M, Nakashima A, Tofuku Y (2000) Electrolyte disorders following massive insulin overdose in a patient with type 2 diabetes. Intern Med 39:55–57.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Badran M, Morsy R, Soliman H, Elnimr T (2016) Assessment of trace elements levels in patients with type 2 diabetes using multivariate statistical analysis. J Trace Elem Med Biol 33:114–119.

    CAS  Article  PubMed  Google Scholar 

  18. 18.

    Barbagallo M, Dominguez LJ, Galioto A et al (2003) Role of magnesium in insulin action, diabetes and cardio-metabolic syndrome X. Mol Asp Med 24:39–52

    CAS  Article  Google Scholar 

  19. 19.

    Samadi A, Isikhan SY, Tinkov AA, Lay I, Doşa MD, Skalny AV, Skalnaya MG, Chirumbolo S, Bjørklund G (2019) Zinc, copper, and oxysterol levels in patients with type 1 and type 2 diabetes mellitus. Clin Nutr 39:1849–1856.

    CAS  Article  PubMed  Google Scholar 

  20. 20.

    Sobczak AIS, Stefanowicz F, Pitt SJ, Ajjan RA, Stewart AJ (2019) Total plasma magnesium, zinc, copper and selenium concentrations in type-I and type-II diabetes. BioMetals 32:123–138.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Khan FA, Al Jameil N, Arjumand S et al (2015) Comparative study of serum copper, Iron, magnesium, and zinc in type 2 diabetes-associated proteinuria. Biol Trace Elem Res 168:321–329.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Tonelli M, Wiebe N, Hemmelgarn B et al (2009) Trace elements in hemodialysis patients: a systematic review and meta-analysis. BMC Med 7:25

    Article  Google Scholar 

  23. 23.

    Jankowska M, Rutkowski B, Dębska-Ślizień A (2017) Vitamins and microelement bioavailability in different stages of chronic kidney disease. Nutrients 9.

  24. 24.

    Treviño S, Sánchez-Lara E, Sarmiento-Ortega VE, Sánchez-Lombardo I, Flores-Hernández JÁ, Pérez-Benítez A, Brambila-Colombres E, González-Vergara E (2015) Hypoglycemic, lipid-lowering and metabolic regulation activities of metforminium decavanadate (H2Metf)3 [V10O28]·8H2O using hypercaloric-induced carbohydrate and lipid deregulation in Wistar rats as biological model. J Inorg Biochem 147:85–92.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Treviño S, Vázquez-Roque RA, López-López G, Perez-Cruz C, Moran C, Handal-Silva A, González-Vergara E, Flores G, Guevara J, Díaz A (2017) Metabolic syndrome causes recognition impairments and reduced hippocampal neuronal plasticity in rats. J Chem Neuroanat 82:65–75.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Diaz A, Escobedo C, Treviño S, Chávez R, Lopez-Lopez G, Moran C, Guevara J, Venegas B, Muñoz-Arenas G (2018) Metabolic syndrome exacerbates the recognition memory impairment and oxidative-inflammatory response in rats with an intrahippocampal injection of amyloid beta 1-42. Oxidative Med Cell Longev 2018:1358057–1358013.

    CAS  Article  Google Scholar 

  27. 27.

    Santamaria-Juarez C, Atonal-Flores F, Diaz A et al (2020) Aortic dysfunction by chronic cadmium exposure is linked to multiple metabolic risk factors that converge in anion superoxide production. Arch Physiol Biochem:1–9.

  28. 28.

    Treviño S, Aguilar-Alonso P, Flores Hernandez JA, Brambila E, Guevara J, Flores G, Lopez-Lopez G, Muñoz-Arenas G, Morales-Medina JC, Toxqui V, Venegas B, Diaz A (2015) A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats. Synapse 69:421–433.

    CAS  Article  PubMed  Google Scholar 

  29. 29.

    Sarmiento-Ortega V, Brambila E, Flores-Hernández J, Díaz A, Peña-Rosas U, Moroni-González D, Aburto-Luna V, Treviño S (2018) The NOAEL metformin dose is ineffective against metabolic disruption induced by chronic cadmium exposure in Wistar rats. Toxics 6:55.

    CAS  Article  PubMed Central  Google Scholar 

  30. 30.

    Treviño S, Waalkes MP, Flores Hernández JA, León-Chavez BA, Aguilar-Alonso P, Brambila E (2015) Chronic cadmium exposure in rats produces pancreatic impairment and insulin resistance in multiple peripheral tissues. Arch Biochem Biophys 583:27–35.

    CAS  Article  PubMed  Google Scholar 

  31. 31.

    Farriol M, Rosselló J, Schwartz S (1997) Body surface area in Sprague-Dawley rats. J Anim Physiol Anim Nutr (Berl) 77:61–65.

    Article  Google Scholar 

  32. 32.

    Raij L, Azar S, Keane W (1984) Mesangial immune injury, hypertension, and progressive glomerular damage in Dahl rats. Kidney Int 26:137–143.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Nishiyama A, Yoshizumi M, Hitomi H et al (2004) The SOD mimetic tempol ameliorates glomerular injury and reduces mitogen-activated protein kinase activity in Dahl salt-sensitive rats. J Am Soc Nephrol 15:306–315.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Duarte FO, Sene-Fiorese M, Cheik NC, Maria ASLS, de Aquino AE Jr, Oishi JC, Rossi EA, Garcia de Oliveira Duarte AC, Dâmaso AR (2012) Food restriction and refeeding induces changes in lipid pathways and fat deposition in the adipose and hepatic tissues in rats with diet-induced obesity. Exp Physiol 97:882–894.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Westerterp KR (2006) Perception, passive overfeeding and energy metabolism. Physiol Behav 89:62–65.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Lejk A, Myśliwiec M, Myśliwiec A (2019) Effect of eating resistant starch on the development of overweight, obesity, and disorders of carbohydrate metabolism in children. Pediatr Endocrinol Diabetes Metab 25:81–84.

    Article  PubMed  Google Scholar 

  37. 37.

    Liao CC, Sheu WHH, Lin SY, Lee WJ, Lee IT (2020) The relationship between abdominal body composition and metabolic syndrome after a weight reduction program in adult men with obesity. Diabetes Metab Syndr Obes Targets Ther 13:1–8.

    CAS  Article  Google Scholar 

  38. 38.

    Qiu Y, Zhao Q, Gu Y, Wang N, Yu Y, Wang R, Zhang Y, Zhu M, Liu X, Jiang Y, Zhao G (2019) Association of metabolic syndrome and its components with decreased estimated glomerular filtration rate in adults. Ann Nutr Metab 75:168–178.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Thomas G, Sehgal AR, Kashyap SR, Srinivas TR, Kirwan JP, Navaneethan SD (2011) Metabolic syndrome and kidney disease: a systematic review and meta-analysis. Clin J Am Soc Nephrol 6:2364–2373.

    Article  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Rashidbeygi E, Safabakhsh M, Delshadaghdam S et al (2019) Metabolic syndrome and its components are related to a higher risk for albuminuria and proteinuria: evidence from a meta-analysis on 10,603,067 subjects from 57 studies. Diabetes Metab Syndr Clin Res Rev 13:830–843

    Article  Google Scholar 

  41. 41.

    Chen J, Kong X, Jia X, Li W, Wang Z, Cui M, Xu D (2017) Association between metabolic syndrome and chronic kidney disease in a Chinese urban population. Clin Chim Acta 470:103–108.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Lerman LO, Lerman A (2011) The metabolic syndrome and early kidney disease: another link in the chain? Rev Esp Cardiol 64:358–360.

    Article  PubMed  PubMed Central  Google Scholar 

  43. 43.

    El-Khashab SO, Gamil M, Ali AY et al (2019) Chemerin level and the relation to insulin resistance in chronic kidney disease. Saudi J Kidney Dis Transpl 30:1381–1388.

    Article  PubMed  Google Scholar 

  44. 44.

    Spoto B, Pisano A, Zoccali C (2016) Insulin resistance in chronic kidney disease: a systematic review. Am J Physiol Ren Physiol 311:F1087–F1108

    CAS  Article  Google Scholar 

  45. 45.

    Xu H, Carrero JJ (2017) Insulin resistance in chronic kidney disease. Nephrology 22:31–34

    CAS  Article  Google Scholar 

  46. 46.

    Lee MJ, Feliers D, Mariappan MM, Sataranatarajan K, Mahimainathan L, Musi N, Foretz M, Viollet B, Weinberg JM, Choudhury GG, Kasinath BS (2007) A role for AMP-activated protein kinase in diabetes-induced renal hypertrophy. Am J Physiol Ren Physiol 292:292–F627.

    CAS  Article  Google Scholar 

  47. 47.

    Kim Y, Park CW (2019) Mechanisms of adiponectin action: implication of adiponectin receptor agonism in diabetic kidney disease. Int J Mol Sci 20

  48. 48.

    Shen YY, Peake PW, Charlesworth JA (2008) Review article: adiponectin: its role in kidney disease. Nephrology 13:528–534

    CAS  Article  Google Scholar 

  49. 49.

    Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn BB, Kadowaki T (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Ouedraogo R, Wu X, Xu S-Q, Fuchsel L, Motoshima H, Mahadev K, Hough K, Scalia R, Goldstein BJ (2006) Adiponectin suppression of high-glucose-induced reactive oxygen species in vascular endothelial cells: evidence for involvement of a cAMP signaling pathway. Diabetes 55:1840–1846.

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Zhang Y, Yang S, Cui X, Yang J, Zheng M, Jia J, Han F, Yang X, Wang J, Guo Z, Chang B, Chang B (2019) Hyperinsulinemia can cause kidney disease in the IGT stage of OLETF rats via the INS/IRS-1/PI3-K/Akt signaling pathway. J Diabetes Res 2019:1–12.

    CAS  Article  Google Scholar 

  52. 52.

    Isshiki K, He Z, Maeno Y, Ma RC, Yasuda Y, Kuroki T, White GS, Patti ME, Weir GC, King GL (2008) Insulin regulates SOCS2 expression and the mitogenic effect of IGF-1 in mesangial cells. Kidney Int 74:1434–1443.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  53. 53.

    Masson E, Wiernsperger N, Lagarde M, El Bawab S (2005) Glucosamine induces cell-cycle arrest and hypertrophy of mesangial cells: implication of gangliosides. Biochem J 388:537–544.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Thrailkill KM, Clay Bunn R, Fowlkes JL (2009) Matrix metalloproteinases: their potential role in the pathogenesis of diabetic nephropathy. Endocrine 35:1–10

    CAS  Article  Google Scholar 

  55. 55.

    Mariappan MM, De Silva K, Sorice GP et al (2014) Combined acute hyperglycemic and hyperinsulinemic clamp induced profibrotic and proinflammatory responses in the kidney. Am J Phys Cell Physiol 306:C202–C211.

    CAS  Article  Google Scholar 

  56. 56.

    Higgins SP, Tang Y, Higgins CE, Mian B, Zhang W, Czekay RP, Samarakoon R, Conti DJ, Higgins PJ (2018) TGF-β1/p53 signaling in renal fibrogenesis. Cell Signal 43:1–10

    CAS  Article  Google Scholar 

  57. 57.

    Kim S II, Choi ME (2012) TGF-β-activated kinase-1: new insights into the mechanism of TGF-β signaling and kidney disease. Kidney Res Clin Pract 31:94–105

    Article  Google Scholar 

  58. 58.

    Morrisey K, Evans RA, Wakefield L, Phillips AO (2001) Translational regulation of renal proximal tubular epithelial cell transforming growth factor-β1 generation by insulin. Am J Pathol 159:1905–1915.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Waheed F, Dan Q, Amoozadeh Y, Zhang Y, Tanimura S, Speight P, Kapus A, Szászi K (2013) Central role of the exchange factor GEF-H1 in TNF-α-induced sequential activation of Rac, ADAM17/TACE, and RhoA in tubular epithelial cells. Mol Biol Cell 24:1068–1082.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Vallon V (2011) The proximal tubule in the pathophysiology of the diabetic kidney. Am J Phys Regul Integr Comp Phys 300:R1009

    CAS  Google Scholar 

  61. 61.

    Liu Y, Huang H, Gao R, Liu Y (2020) Dynamic phenotypes and molecular mechanisms to understand the pathogenesis of diabetic nephropathy in two widely used animal models of type 2 diabetes mellitus. Front Cell Dev Biol 8.

  62. 62.

    Nunes S, Alves A, Preguiça I, Barbosa A, Vieira P, Mendes F, Martins D, Viana SD, Reis F (2020) Crescent-like lesions as an early signature of nephropathy in a rat model of prediabetes induced by a hypercaloric diet. Nutrients 12:12.

    CAS  Article  Google Scholar 

  63. 63.

    Aghadavod E, Soleimani A, Amirani E, Gholriz Khatami P, Akasheh N, Sharafati Chaleshtori R, Shafabakhsh R, Banikazemi Z, Asemi Z (2020) Comparison between biomarkers of kidney injury, inflammation, and oxidative stress in patients with diabetic nephropathy and type 2 diabetes mellitus. Iran J Kidney Dis 14:31–35

    PubMed  Google Scholar 

  64. 64.

    Gill V, Kumar V, Singh K et al (2019) Advanced glycation end products (AGEs) may be a striking link between modern diet and health. Biomolecules:9

  65. 65.

    Savelieff MG, Callaghan BC, Feldman EL (2020) The emerging role of dyslipidemia in diabetic microvascular complications. Curr Opin Endocrinol Diabetes Obes 27:115–123

    CAS  Article  Google Scholar 

  66. 66.

    Wang Z, Jiang T, Li J, Proctor G, McManaman JL, Lucia S, Chua S, Levi M (2005) Regulation of renal lipid metabolism, lipid accumulation, and glomerulosclerosis in FVBdb/db mice with type 2 diabetes. Diabetes 54:2328–2335.

    CAS  Article  PubMed  Google Scholar 

  67. 67.

    Hirano T (2018) Pathophysiology of diabetic dyslipidemia. J Atheroscler Thromb 25:771–782

    CAS  Article  Google Scholar 

  68. 68.

    Chevalier RL (2016) The proximal tubule is the primary target of injury and progression of kidney disease: role of the glomerulotubular junction. Am J Physiol Ren Physiol 311:F145–F161

    CAS  Article  Google Scholar 

  69. 69.

    Hallow KM, Gebremichael Y, Helmlinger G, Vallon V (2017) Primary proximal tubule hyperreabsorption and impaired tubular transport counterregulation determine glomerular hyperfiltration in diabetes: a modeling analysis. Am J Physiol Ren Physiol 312:F819–F835.

    CAS  Article  Google Scholar 

  70. 70.

    Gilbert RE (2017) Proximal tubulopathy: prime mover and key therapeutic target in diabetic kidney disease. Diabetes 66:791–800

    CAS  Article  Google Scholar 

  71. 71.

    Resnick LM, Barbagallo M, Gupta RK, Laragh JH (1993) Ionic basis of hypertension in diabetes mellitus. Role of hyperglycemia. Am J Hypertens 6:413–417.

    CAS  Article  PubMed  Google Scholar 

  72. 72.

    Aguilar MV, Saavedra P, Arrieta FJ, Mateos CJ, González MJ, Meseguer I, Martínez-Para MC (2007) Plasma mineral content in type-2 diabetic patients and their association with the metabolic syndrome. Ann Nutr Metab 51:402–406.

    CAS  Article  PubMed  Google Scholar 

  73. 73.

    Karganov MY, Alchinova IB, Tinkov AA, Medvedeva YS, Lebedeva MA, Ajsuvakova OP, Polyakova MV, Skalnaya MG, Burtseva TI, Notova SV, Khlebnikova NN, Skalny AV (2020) Streptozotocin (STZ)-induced diabetes affects tissue trace element content in rats in a dose-dependent manner. Biol Trace Elem Res.

  74. 74.

    Tinkov AA, Gatiatulina ER, Popova EV, Polyakova VS, Skalnaya AA, Agletdinov EF, Nikonorov AA, Skalny AV (2017) Early high-fat feeding induces alteration of trace element content in tissues of juvenile male Wistar rats. Biol Trace Elem Res 175:367–374.

    CAS  Article  PubMed  Google Scholar 

  75. 75.

    Farhadnejad H, Asghari G, Mirmiran P, Yuzbashian E, Azizi F (2016) Micronutrient intakes and incidence of chronic kidney disease in adults: Tehran lipid and glucose study. Nutrients 8:217.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  76. 76.

    Martín-del-Campo F, Batis-Ruvalcaba C, González-Espinoza L et al (2012) Dietary micronutrient intake in peritoneal dialysis patients: relationship with nutrition and inflammation status. Perit Dial Int 32:183–191.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  77. 77.

    Bossola M, Di Stasio E, Viola A et al (2014) Dietary intake of trace elements, minerals, and vitamins of patients on chronic hemodialysis. Int Urol Nephrol 46:809–815.

    CAS  Article  PubMed  Google Scholar 

  78. 78.

    Tang X, Shay NF (2001) Zinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes. J Nutr 131:1414–1420.

    CAS  Article  PubMed  Google Scholar 

  79. 79.

    Eshed I, Elis A, Lishner M (2001) Plasma ferritin and type 2 diabetes mellitus: a critical review. Endocr Res 27:91–97.

    CAS  Article  PubMed  Google Scholar 

  80. 80.

    Haap M, Fritsche A, Mensing HJ, Hring HU, Stumvoll M (2003) Association of high serum ferritin concentration with glucose intolerance and insulin resistance in healthy people. Ann Intern Med 139:869–871

    Article  Google Scholar 

  81. 81.

    Kazi TG, Afridi HI, Kazi N, Jamali MK, Arain MB, Jalbani N, Kandhro GA (2008) Copper, chromium, manganese, iron, nickel, and zinc levels in biological samples of diabetes mellitus patients. Biol Trace Elem Res 122:1–18.

    CAS  Article  PubMed  Google Scholar 

  82. 82.

    Kaur B, Henry J (2014) Micronutrient status in type 2 diabetes: a review. Adv Food Nutr Res 71:55–100.

    CAS  Article  PubMed  Google Scholar 

  83. 83.

    Wilson JG, Lindquist JH, Grambow SC, et al (2003) Potential role of increased iron stores in diabetes. In: American Journal of the Medical Sciences. Lippincott Williams and Wilkins, pp. 332–339

  84. 84.

    Mooren FC, Krüger K, Völker K, Golf SW, Wadepuhl M, Kraus A (2011) Oral magnesium supplementation reduces insulin resistance in non-diabetic subjects - a double-blind, placebo-controlled, randomized trial. Diabetes. Obes Metab 13:281–284

    CAS  Article  Google Scholar 

  85. 85.

    Guerrero-Romero F, Tamez-Perez HE, González-González G, Salinas-Martínez AM, Montes-Villarreal J, Treviño-Ortiz JH, Rodríguez-Morán M (2004) Oral magnesium supplementation improves insulin sensitivity in non-diabetic subjects with insulin resistance. A double-blind placebo-controlled randomized trial. Diabetes Metab 30:253–258.

    CAS  Article  PubMed  Google Scholar 

  86. 86.

    Korc M (1983) Manganese action on pancreatic protein synthesis in normal and diabetic rats. Am J Physiol Gastrointest Liver Physiol 8:G628–G634.

    Article  Google Scholar 

  87. 87.

    Juanola-Falgarona M, Cándido-Fernández J, Salas-Salvadó J, Martínez-González MA, Estruch R, Fiol M, Arija-Val V, Bulló M, for the PREDIMED Study Investigators (2013) Association between serum ferritin and osteocalcin as a potential mechanism explaining the iron-induced insulin resistance. PLoS One 8:8.

    CAS  Article  Google Scholar 

  88. 88.

    Vallon V, Thomson SC (2012) Renal function in diabetic disease models: the tubular system in the pathophysiology of the diabetic kidney. Annu Rev Physiol 74:351–375.

    CAS  Article  PubMed  Google Scholar 

  89. 89.

    Barbato A, Cappuccio FP, Folkerd EJ, Strazzullo P, Sampson B, Cook DG, Alberti KGMM (2004) Metabolic syndrome and renal sodium handling in three ethnic groups living in England. Diabetologia 47:40–46.

    CAS  Article  PubMed  Google Scholar 

  90. 90.

    Cappuccio FP, Strazzullo P, Siani A, Trevisan M (1996) Increased proximal sodium reabsorption is associated with increased cardiovascular risk in men. J Hypertens 14:909–914.

    CAS  Article  PubMed  Google Scholar 

  91. 91.

    Vallon V, Huang DY, Deng A et al (2002) Salt-sensitivity of proximal reabsorption alters macula densa salt and explains the paradoxical effect of dietary salt on glomerular filtration rate in diabetes mellitus. J Am Soc Nephrol 13:1865–1871.

    Article  PubMed  Google Scholar 

  92. 92.

    Vallon V, Thomson SC (2020) The tubular hypothesis of nephron filtration and diabetic kidney disease. Nat Rev Nephrol 16:317–336

    CAS  Article  Google Scholar 

  93. 93.

    Makhlough A, Makhlough M, Shokrzadeh M, Mohammadian M, Sedighi O, Faghihan M (2015) Comparing the levels of trace elements in patients with diabetic nephropathy and healthy individuals. Nephrourol Mon 7:e28576.

    Article  PubMed  PubMed Central  Google Scholar 

  94. 94.

    Al-Timimi DJ, Sulieman DM, Hussen KR (2014) Zinc status in type 2 diabetic patients: relation to the progression of diabetic nephropathy. J Clin Diagnostic Res 8:CC04

    Google Scholar 

  95. 95.

    Dahan I, Thawho N, Farber E et al (2018) The Iron-Klotho-VDR Axis is a major determinant of proximal convoluted tubule injury in Haptoglobin 2-2 genotype diabetic nephropathy patients and mice. J Diabetes Res 2018.

  96. 96.

    Dominguez JH, Liu Y, Kelly KJ (2015) Renal iron overload in rats with diabetic nephropathy. Physiol Rep 3.

  97. 97.

    Lu Q, Zhai Y, Cheng Q, Liu Y, Gao X, Zhang T, Wei Y, Zhang F, Yin X (2013) The Akt-FoxO3a-manganese superoxide dismutase pathway is involved in the regulation of oxidative stress in diabetic nephropathy. Exp Physiol 98:934–945.

    CAS  Article  PubMed  Google Scholar 

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Authors thank Dr. Francisco Ramos Collazo (Bioterio “Claude Bernard”, BUAP) for his assistance and the donation of the animals used in this work. We express our gratitude to Clinical Laboratory “Los Ángeles” by the facilities to realize the biochemical determinations. Thanks to Professor Thomas Edwards PhD., for editing the English language text.


The Vicerrectoria de Investigación y Posgrado [VIEP; TRMS-NAT19-1] through Ygnacio Martınez Laguna, CONACyT and the “Sistema Nacional de Investigadores” of Mexico provided financial support for this research project [CNSS, 000536].

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Correspondence to Samuel Treviño.

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Sánchez-Solís, C.N., Hernández-Fragoso, H., Aburto-Luna, V. et al. Kidney Adaptations Prevent Loss of Trace Elements in Wistar Rats with Early Metabolic Syndrome. Biol Trace Elem Res 199, 1941–1953 (2021).

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  • Metabolic syndrome
  • Chronic kidney disease
  • Hypercaloric diet
  • Trace elements
  • Micronutrients