Daño renal asociado a metales pesados: trabajo de revisión

Juan Daniel Díaz García, Emmanuel Arceo


La enfermedad renal crónica (ERC) representa un importante problema de salud en todo el globo. Actualmente, es esencial para su prevención el conocimiento de los factores ambientales asociados con la enfermedad. Se reconocen diversos metales pesados, entre los que destacan el cadmio (Cd), plomo (Pb), arsénico (As) y mercurio (Hg), que están claramente asociados con la lesión renal y la progresión de la ERC. Estudios en animales y humanos demuestran, principalmente, una clara asociación entre la exposición a estos metales y la presencia de daño renal crónico, donde la fisiopatología de cada uno de ellos es importante para entender el mecanismo de daño renal. La presente revisión tiene como objetivo analizar, tanto la fisiopatología y manifestaciones clínicas de la nefrotoxicidad asociada a dichos metales, como los diferentes estudios que se han realizado en humanos y animales.


Palabras clave

Nefrotoxicidad, cadmio, plomo, arsénico, mercurio, necrosis tubular aguda, enfermedad renal crónica, metales pesados.


Ferraro PM, Costanzi S, Naticchia A, et al. Low-level exposure to cadmium increases the risk of chronic kidney disease: Analysis of the NHANES 1999–2006. BMC Public Health. 2010; 10:304.

Weaver VM, Kim NS, Jaar BG, et al. Associations of low-level urine cadmium with kidney function in lead workers. Occup Environ Med. 2011; 68:250–256.

Fujishiro H, Okugaki S, Kubota K, Fujiyama T, Himeno S. The role of ZIP8 down-regulation in cadmium-resistant metallothionein-null cells. J Appl Toxicol 2009; 29:367-73.

Thévenod F. Catch me if you can! Novel aspects of cadmium transport n mammalian cells. Biometals. 2010; 23:857-75.

Liu Y, Liu J, Klaassen CD. Metallothionein-null and wild-type mice show similar cadmium absorption and tissue distribution following oral cadmium administration. Toxicol Appl Pharmacol. 2001; 175:253-9.

Olivi L, Sisk J, Bressler J. Involvement of DMT1 in uptake of Cd in MDCK cells: role of protein kinase C. Am J Physiol Cell Physiol. 2001; 281:C793-800.

Hirano S, Sun X, DeGuzman C, Ransom R, MacLeish K, Smoyer WE, et al. p38 MAPK/ HSP25 signaling mediates cadmium-induced contraction of mesangial cells and renal glomeruli. Am J Physiol Renal Physiol. 2005; 288:F1133-43.

Gunawardana CG, Martínez RE, Xiao W, Templeton DM. Cadmium inhibits both intrinsic and extrinsic apoptotic pathways in renal mesangial cells. Am J Physiol Renal Physiol. 2006; 290:F1074-82.

Klaassen CD, Liu J, Diwan BA. Metallothionein protection of cadmium toxicity. Toxicol Appl Pharmacol. 2009; 238:215-20.

Ekong EB, Jaar BG, Weaver VM. Lead-related nephrotoxicity: A review of the epidemiologic evidence. Kidney Int. 2006; 70:2074-84.

Wang L, Wang H, Hu M, Cao J, Chen D, Liu Z. Oxidative stress and apoptotic changes in primary cultures of rat proximal tubular cells exposed to lead. Arch Toxicol. 2009;83:417-27.

Chiu TY, Teng HC, Huang PC, Kao FJ, Yang DM. Dominant role of Orai1 with STIM1 on the cytosolic entry and cytotoxicity of lead ions. Toxicol Lett. 2009; 110:353-62.

Handlogten M, Shiraishi N, Awata H, Huang C, Tyler-Miller R. Extracellular Ca2-sensing receptor is a promiscuous divalent cation sensor that responds to lead. Am J Physiol Renal Physiol. 2000;279:F1083-91.

Bravo Y, Quiroz Y, Ferrebuz A, Vaziri N, Rodríguez-Iturbe B. Mycophenolate mofetil administration reduces renal inflammation, oxidative stress, and arterial pressure in rats with lead-induced hypertension. Am J Physiol Renal Physiol. 2007; 293:F616-23.

Vaziri N. Mechanisms of lead-induced hypertension and cardiovascular disease. Am J Physiol Heart Circ Physiol. 2008; 295:H454-

Courtois E, Marques M, Barrientos A, Casado S, López-Farré A. Lead-induced downregulation of soluble guanylate cyclase in isolated rat aortic segments mediated by reactive oxygen species and cyclooxygenase-2. J Am Soc Nephrol. 2003; 14:1464-70.

Ni Z, Hou S, Barton C, Vaziri N. Lead exposure raises superoxide and hydrogen peroxide in human endothelial and vascular smooth muscle cells. Kidney Int. 2004; 66:2329-36.

Thomas D. Unraveling arsenic-glutathione connections. Toxicol Sci 2009;107:309-11. Carbrey JM, Song L, Zhou Y, Yoshinaga M, Rojek A. Reduced arsenic clearance and increased toxicity in aquaglyceroporin-9-null mice. Proc Natl Acad Sci USA. 2009;106:15956-60.

Lee TC, Ho IC, Lu WJ, Huang JD. Enhanced expression of multidrug resistance-associated protein 2 and reduced expression of aquaglyceroporin-3 in an arsenic-resistant human cell line. J Biol Chem 2006;281:18401-7.

Gonick HC. Nephropathies in heavy metal intoxication. In: Massry SG, Glassock RJ. 4th Edición. Lippincott William &Wilkins, Philadelphia,2001. Pp. 933-934.

Hill G. Drug-associated glomerulopathies. Toxicol Pathol. 1986;14: 37-44.

Aymaz S, Gros O, Krakamp B, et al. Membranous nephropathy from exposure to mercury in the fluorescent-tuberecycling industry. Neprol Dial Transplant. 2001;16: 2253-2255.

Cameron JS, Trounce JR. Membranous glomerulonephritis and the nephrotic syndrome appearing during mersalyl therapy. Guys Hospi Rep. 1965;114: 101-107.

Chakera A, Lasseron D, Beck LH Jr, et al. Membranous nephropathy after use of UK-manufactured skin creams containing mercury. Q J Med 2011; 104: 893-896.

http://www.who.int/mediacentre/factsheets/fs361/en/WHO Mercury and health. Fact sheet N°361.

Oliveira DBG, Foster G, Savill J, et al. Membranous nephropa- thy caused by mercury-containing skin lightening cream. Postgrad Med J. 1987;63: 303-304.

El Azzouzi B, Tsangaris GT, Pellegrini O, Manuel Y, Benveniste J, and Thomas Y. Cadmium induces apoptosis in a human T cell line. Toxicology. 1994; 88: 127–139.

WC Prozialeck, VS Vaidya, J Liu, MP Waalkes, JR Edwards, PC Lamar, AM Bernard, X Dumont, and JV Bonventre. Kidney injury molecule-1 is an early biomarker of cadmium nephrotoxicity. Kidney Int. 2007; 72(8): 985–993.

Ziqiang Meng, Guohua Qin, Bo Zhang, Juli Bai. DNA damaging effects of sulfur dioxide derivatives in cells from various organs of mice. Mutagenesis. 2004; 19(6): 465-468.

P. C. Brazy, R. S. Balaban, S. R. Gullans, L. J. Nmiandel, V. AT. dennia. Relative effects of arsenate on sodium, phosphate, and glucose transport by the rabbit proximal tubule. J Clin Invest. 1980;66:1211-1221.

Jiangang Hou et al. 5-Aminolevulinic acid combined with ferrous iron induces carbon monoxide generation in mouse kidneys and protects from renal ischemia-reperfusion injury. Am J Physiol. 2013. 305:F1149-F1157.

Puri VN, Saha S. Comparison of acute cardiovascular effects of cadmium and captopril in relation to oxidant and angiotensin converting enzyme activity in rats. Drug Chem Toxicol. 2003;26(3):213–218.

Chen Y, Graziano JH, Parvez F, Liu M, Slavkovich V, Kalra T, et al. Arsenic exposure from drinking water and mortality from cardiovascular disease in Bangladesh: prospective cohort study. BMJ. 2011;342:d2431; doi: 10.1136/bmj.d2431 [Online 5 May2011].

Lewis DR, Southwick JW, Ouellet-Hellstrom R, et al. Drinking water arsenic in Utah: A cohort mortality study. Environ Health Perspect. 1999;107:359–365.

Meliker JR, Wahl RL, Cameron LL, et al. Arsenic in drinking water and cerebrovascular disease, diabetes mellitus, and kidney disease in Michigan: A standardized mortality ratio analysis. Environ Health. 2007;6:4.

Hsueh YM, Chung CJ, Shiue HS, et al. Urinary arsenic species and CKD in a Taiwanese population: A case-control study. Am J Kidney Dis. 2009;54:859–870.

Bunderson M, Coffin JD, Beall HD. Arsenic induces peroxynitrite generation and cyclooxygenase-2 protein expression in aortic endothelial cells: possible role in atherosclerosis. Toxicol Appl Pharmacol. 2002;184:11–18.

Carmignani M, Boscolo P, Castellino N. Metabolic fate and cardiovascular effects of arsenic in rats and rabbits chroni- cally exposed to trivalent and pentavalent arsenic. Arch Toxicol. 1985;(Suppl 8):452–455.

Chen Y, Factor-Litvak P, Howe GR, Graziano JH, Brandt-Rauf P, Parvez F, et al. Arsenic exposure from drinking water, dietary intakes of B vitamins and folate, and risk of high blood pressure in Bangladesh: a population-based, cross-sectional study. Am J Epidemiol. 2017;165:541–552.

Druwe IL, Vaillancourt RR. Influence of arsenate and arsenite on signal transduction pathways: an update. Arch Toxicol. 2010;84:585–596.

Walton FS, Harmon AW, Paul DS, Drobna Z, Patel YM, Styblo M: Inhibition of insulin-dependent glucose uptake by trivalent arsenicals: possible mechanism of arsenic-induced diabetes. Toxicol Appl Pharmacol. 2004;198:424-433.

Salazard B, Bellon L, Jean S, Maraninchi M, El Yazidi C, Orsiere T, Mar- gotat A, Botta A, Bergé-Lefranc J-L: Low-level arsenite activates the transcription of genes involved in adipose differentiation. Cell Biol Toxicol. 2004;20:375-385.

Yoopan N, Watcharasit P, Wongsawatkul O, Piyachaturawat P, atayavivad J. Attenuation of eNOS expression in cadmium- induced hypertensive rats. Toxicol Lett. 2018;176(2):157–161.

Mueller PW, Price RG, Finn WF. New approaches for detecting thresholds of human nephrotoxicity using cadmium as an example. Environ Health Perspect. 1998;106:227– 230.

Lauwerys RR, Bernard AM, Roels HA, Buchet JP. Cadmium: exposure markers as predictors of nephro-toxic effects. Clin Chem. 1994;40:1391–1394.

Roels H, Djubgang J, Buchet JP, Bernard A, Lauwerys R. Evolution of cadmium-induced renal dysfunction in workers removed from exposure. Scand J Work Environ Health. 1982; 8:191–200.

Roels HA, Lauwerys RR, Buchets JP, Bernard AM, Vos A, Oversteyns M. Health significance of cadmium-induced renal dysfunction: a five-year follow up. Br J Ind Med. 1989; 46:755–764.

Mueller PW, Paschal DC, Hammel RR, Klincewicz SL, MacNeil ML, Spierto B, Steinberg KK. Chronic renal effects in three studies of men and women occupationally exposed to cadmium. Arch Environ Contam Toxicol. 1992;23:125–136.

Ja-Liang Lin, Dan-Tzu Lin-Tan, Kuang-Hung Hsu, Chun-Chen Yu. Environmental Lead Exposure and Progression of Chronic Renal Diseases in Patients without Diabetes. N Engl J Med. 2003;348:277-86.

Johan Nilsson Sommar, Maria K Svensson, Bodil M Björ, Sölve I Elmståhl, Göran Hallmans, Thomas Lundh, Staffan MI Schön, Staffan Skerfving, Ingvar A Bergdahl. End-stage renal disease and low-level exposure to lead, cadmium and mercury; a population based, prospective nested case-referent study in Sweden. Environmental Health. 2013; 12:9.

Zhenmin Ni, Stephen Hou, Cyril H. Barton, Nosratola D. Vaziri. Lead exposure raises superoxide and hydrogen peroxide in human endothelial and vascular smooth muscle cells. Kidney International. 2004;66:2329–2336.

Yu M, Xue J, Li Y, et al. Resveratrol protects against arsenic trioxide induced nephrotoxicity by facilitating arsenic metabolism and decreasing oxidative stress. Arch Toxicol. 2013; 87:1025–1035.

Bera AK, Rana T, Das S, et al. Mitigation of arsenic-mediated renal oxidative stress in rat by Pleurotus florida lectin. Hum Exp Toxicol. 2011; 30:940–951.

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DOI: 10.22265/acnef.5.2.254

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