Información del artículo
El riñón tiene un papel importante en la síntesis, metabolismo y eliminación de gran cantidad de hormonas. Así, la enfermedad renal crónica (ERC) cursa de forma natural con diversas alteraciones hormonales. Esta revisión aborda la posible conexión entre alteraciones en el eje hipotalámico-pituitario-gonadal y factores de riesgo cardiovascular en el paciente con ERC. Las anomalías hormonales analizadas son la retención de prolactina, deficiencia de testosterona y síndrome de T3 baja, todas ellas entendidas tradicionalmente como testigos inocentes de uremia y que han recibido una atención relativamente escasa por la comunidad nefróloga. En este revisamos interesantes vinculos entre estas alteraciones hormonales y complicaciones como la inflamación sistemica, la disfunción endotelial, la rigidez arterial, el desgaste proteico-energético y otras alteraciones cardiometabólicas inherentes a la excesiva mortalidad observada en la ERC. Proponemos que estas disfunciones hormonales pueden ser nuevos o previamene no apreciados factores de riesgo en el paciente urémico, existiendo la posibilidad de que puedan servir como objetivos terapéuticos.
Palabras clave:
Prolactina
Palabras clave:
Hormonas tiroideas
Palabras clave:
Testosterona
The kidney plays an important role in synthesis, metabolism and elimination of a plethora of hormones. Thus, chronic kidney disease (CKD) naturally progresses with hormonal disorders. This review will focus in emerging evidence regarding the association between CKD-associated disturbances in the hypothalamic-pituitary-gonadal axis and cardiovascular risk factors. Hormonal derangements discussed are prolactin retention, testosterone deficiency and the low trioodothyronine syndrome, all of which have traditionally been interpreted as innocent bystanders of uremia and received relatively scarce attention by the Nephrology community. We here show that these disorders share intriguing links with inflammation, endothelial dysfunction, arterial stiffness, protein-energy wasting and other cardiometabolic alterations inherent to CKD-related excess mortality. We argue that these disorders may be novel uremic risk factors with possibility to serve as therapeutic targets.
Keywords:
Prolactin
Keywords:
Thyroid hormones
Keywords:
Testosterone
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Bibliografía
[1]
Lim VS, Kathpalia SC, Henriquez C. Endocrine abnormalities associated with chronic renal failure. Med Clin North Am 1978;62(6):1341-61. [Pubmed]
[2]
Meuwese CL, Stenvinkel P, Dekker FW, Carrero JJ. Monitoring of inflammation in patients on dialysis: forewarned is forearmed. Nat Rev Nephrol 2011;7(3):166-76. [Pubmed]
[3]
Carrero JJ, Stenvinkel P. Inflammation in end-stage renal disease--what have we learned in 10 years? Semin Dial 2010;23(5):498-509. [Pubmed]
[4]
Iglesias P, Carrero JJ, Díez JJ. Gonadal dysfunction in men with chronic kidney disease: clinical features, prognostic implications and therapeutic options. J Nephrol 2012;25(1):31-42. [Pubmed]
[5]
Carrero JJ, Kyriazis J, Sonmez A, Tzanakis I, Qureshi AR, Stenvinkel P, et al. Prolactin levels, endotelial dysfunction, and the risk of cardiovascular events and mortality in patients with CKD. Clin J Am Soc Nephrol 2012;7:207-15. [Pubmed]
[6]
Stumpe KO, Kolloch R, Higuchi M, Krück F, Vetter H. Hyperprolactinaemia and antihypertensive effect of bromocriptine in essential hypertension. Identification of abnormal central dopamine control. Lancet 1977;2:211-4. [Pubmed]
[7]
Wallaschofski H, Lohmann T, Hild E, Kobsar A, Siegemund A, Spilcke-Liss E, et al. Enhanced platelet activation by prolactin in patients with ischemic stroke. Thromb Haemost 2006;96:38-44. [Pubmed]
[8]
Leaños-Miranda A, Márquez-Acosta J, Cárdenas-Mondragón GM, Chinolla-Arellano ZL, Rivera-Leaños R, Bermejo-Huerta S, et al. Urinary prolactin as a reliable marker for preeclampsia, its severity, and the occurrence of adverse pregnancy outcomes. J Clin Endocrinol Metab 2008;93:2492-9. [Pubmed]
[9]
Gomez F, de la Cueva R, Wauters JP, Lemarchand-Beraud T. Endocrine abnormaltities in patients undergoing long-term hemodialysis: The role of prolactin. Am J Med 1980;68:522-30. [Pubmed]
[10]
Hilfiker-Kleiner D, Kaminski K, Podewski E, Bonda T, Schaefer A, Sliwa K, et al. A cathepsin D-cleaved 16 kDa form of prolactin mediates postpartum cardiomyopathy. Cell 2007;128:589-600. [Pubmed]
[11]
Corona G, Rastrelli G, Boddi V, Monami M, Melani C, Balzi D, et al. Prolactin levels independently predict major cardiovascular events in patients with erectile dysfunction. Int J Androl 2011;34(3):217-24. [Pubmed]
[12]
Haring R, Völzke H, Vasan RS, Felix SB, Nauck M, Dörr M, Wallaschofski H. Sex-specific associations of serum prolactin concentrations with cardiac remodeling: longitudinal results from the Study of Health Pomerania (SHIP). Atherosclerosis 2012;221(2):570-6. [Pubmed]
[13]
Sauro MD, Buckley AR, Russell DH, Fitzpatrick DF. Prolactin stimulation of protein kinase C activity in rat aortic smooth muscle. Life Sci 1989;44:1787-92. [Pubmed]
[14]
Sun R, Li AL, We HM, Tian ZG. Expression of prolactin receptor and response to prolactin stimulation of human NK cell lines. Cell Res 2004;14:67-73. [Pubmed]
[15]
Sliwa K, Blauwet L, Tibazarwa K, Libhaber E, Smedema JP, Becker A, et al. Evaluation of bromocriptine in the treatment of acute severe peripartum cardiomyopathy: A proof-of-concept pilot study. Circulation 2010;121:1465-73. [Pubmed]
[16]
Hilfiker-KleinerD, Meyer GP, Schieffer E, Goldmann B, Podewski E, Struman I, et al. Recovery from postpartum cardiomyopathy in 2 patients by blocking prolactin release with bromocriptine. J Am Coll Cardiol 2007;50:2354-5. [Pubmed]
[17]
Mejía-Rodríguez O, Alvarez-Aguilar C, Vega-Gómez HE, Belio-Caro F, Vargas-Espinosa JM, Paniagua-Sierra JR. Bromocriptine induces regression of left ventricular hypertrophy in peritoneal dialysis patients. Proc West Pharmacol Soc 2005;48:122-5. [Pubmed]
[18]
Massry SG, Goldstein DA, Procci WR, Kletzky OA. Impotence in patients with uremia: A possible role for parathyroid hormone. Nephron 1977;19:305-10. [Pubmed]
[19]
Blumberg A, Wildbolz A, Descowudres C, Hennes U, Dambacher MA, Fischer JA, et al. Influence of 1,25 dihydroxycholecalciferol on sexual dysfunction and related endocrine parameters in patients on maintenance hemodialysis. Clin Nephrol 1980;13:208-14.
[20]
Carrero JJ, Qureshi AR, Nakashima A, Arver S, Parini P, Lindholm B, et al. Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease. Nephrol Dial Transplant 2011;26(1):184-90. [Pubmed]
[21]
Yilmaz MI, Sonmez A, Qureshi AR, Saglam M, Stenvinkel P, Yaman H, et al. Endogenous testosterone, endotelial dysfunction, and cardiovascular events in men with nondialysis chronic kidney disease. Clin J Am Soc Nephrol 2011;6:1617-25. [Pubmed]
[22]
Carrero JJ, Stenvinkel P. The vulnerable man: impact of testosterone deficiency on the uraemic phenotype. Nephrol Dial Transplant 2012;27(11):4030-41. [Pubmed]
[23]
Cigarrán S, Pousa M, Castro MJ, González B, Martínez A, Barril B, et al. Endogenous testosterone, muscle strength and fat-free mass in men with chronic kidney disease. J Ren Nutr. 2012 Oct 6. pii: S1051-2276(12)00174-4.
[24]
Johansen KL, Mulligan K, Schambelan M. Anabolic effects of nandrolone decanoate in patients receiving dialysis: A randomized controlled trial. Jama 1999;281:1275-81. [Pubmed]
[25]
Johansen KL, Painter PL, Sakkas GK, Gordon P, Doyle J, Shubert T. Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: A randomized, controlled trial. J Am Soc Nephrol 2006;17:2307-14. [Pubmed]
[26]
Eiam-Ong S, Buranaosot S, Wathanavaha A, Pansin P. Nutritional effect of nandrolone decanoate in predialysis patients with chronic kidney disease. J Ren Nutr 2007;17:173-8. [Pubmed]
[27]
Carrero JJ, Bárány P, Yilmaz MI, Qureshi AR, Sonmez A, Heimbürger O, et al. Testosterone deficiency is a cause of anaemia and reduced responsiveness to erythropoiesis-stimulating agents in men wiht chronic kidney disease. Nephrol Dial Transplant 2012;27(2):709-15. [Pubmed]
[28]
Bachman E, Feng R, Travison T, Li M, Olbina G, Ostland V, et al. Testosterone suppresses hepcidin in men: a potential mechanism for testosterone-induced erythrocytosis. J Clin Endocrinol Metab 2010;95:4743-7. [Pubmed]
[29]
Kyriazis J, Tzanakis I, Stylianou K, Katsipi I, Moisiadis D, Papadaki A, et al. Low serum testosterone, arterial stiffness and mortality in male haemodialysis patients. Nephrol Dial Transplant 2011;26(9):2971-7. [Pubmed]
[30]
Gungor O, Kircelli F, Carrero JJ, Asci G, Toz H, Tatar E, et al. Endogenous testosterone and mortality in male hemodialysis patients: Is It the result of aging? Clin J Am Soc Nephrol 2010;5(1):2018-23. [Pubmed]
[31]
Carrero JJ, Qureshi AR, Parini P, Arver S, Lindholm B, Bárány P, et al. Low serum testosterone increases mortality risk among male dialysis patients. J Am Soc Nephrol 2009;20:613-20. [Pubmed]
[32]
Nettleship JE, Jones TH, Channer KS, Jones RD. Physiological testosterone replacement therapy attenuates fatty streak formation and improves high-density lipoprotein cholesterol in the Tfm mouse: an effect that is independent of the classic androgen receptor. Circulation 2007;116(21):2427-34. [Pubmed]
[33]
Foresta C, Zuccarello D, De Toni L, Garolla A, Caretta N, Ferlin A. Androgens stimulate endothelial progenitor cells through an androgen receptor-mediated pathway. Clin Endocrinol (Oxf) 2008;68(2):284-9.
[34]
Liu D, Dillon JS. Dehydroepiandrosterone stimulates nitric oxide release in vascular endothelial cells: evidence for a cell surface receptor. Steroids 2004;69(4):279-89. [Pubmed]
[35]
Webb CM, Elkington AG, Kraidly MM, Keenan N, Pennell DJ, Collins P. Effects of oral testosterone treatment on myocardial perfusion and vascular function in men with low plasma testosterone and coronary heart disease. Am J Cardiol 2008;101(5):618-24. [Pubmed]
[36]
Carrero JJ, Park SH, Axelsson J, Lindholm B, Stenvinkel P. Cytokines, atherogenesis, and hypercatabolism in chronic kidney disease: a dreadful triad. Semin Dial 2009;22(4):381-6. [Pubmed]
[37]
Fukata J, Imura H, Nakao K. Cytokines as mediators in the regulation of the hypothalamic-pituitary-adrenocortical function. J Endocrinol Invest 1994;17(2):141-55. [Pubmed]
[38]
Malkin CJ, Pugh PJ, Jones RD, Kapoor D, Channer KS, Jones TH. The effect of testosterone replacement on endogenous inflammatory cytokines and lipid profiles in hypogonadal men. J Clin Endocrinol Metab 2004;89(7):3313-8. [Pubmed]
[39]
Corrales JJ, Almeida M, Burgo R, Mories MT, Miralles JM, Orfao A. Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency. J Endocrinol 2006;189(3):595-604. [Pubmed]
[40]
Kalinchenko SY, Tishova YA, Mskhalaya GJ, Gooren LJ, Giltay EJ, Saad F. Effects of testosterone supplementation on markers of the metabolic syndrome and inflammation in hypogonadal men with the metabolic syndrome: the double-blinded placebo-controlled Moscow study. Clin Endocrinol (Oxf) 2010;73(5):602-12.
[41]
Zoccali C, Mallamaci F, Tripepi G, Cutrupi S, Pizzini P. Low triiodothyronine and survival in end-stage renal disease. Kidney Int 2006;70:523-8. [Pubmed]
[42]
Carrero JJ, Qreshi AR, Axelsson J, Yilmaz MI, Rehnmark S, Witt Mr, et al. Clinical and biochemical implications of low thyroid hormone levels (total and free forms) in euthyroid patients with chronic kidney disease. J Intern Med 2007;262(6):690-701. [Pubmed]
[43]
Tatar E, Kircelli F, Asci G, Carrero JJ, Gungor O, Demirci MS, et al. Associations of triiodothyronine levels with carotid aterosclerosis and arterial stiffness in hemodialisysis patients. Clin J Am Soc Nephrol 2011;6(9):2240-6. [Pubmed]
[44]
Chonchol M, Lippi G, Salvagno G, Zoppini G, Muggeo M, Targher G. Prevalence of subclinical hypothyroidism in patients with chronic kidney disease. Clin J Am Soc Nephrol 2008;3(5):1296-300. [Pubmed]
[45]
Meuwese CL, Dekker FW, Lindholm B, Qureshi AR, Heimburger O, Barany P, et al. Baseline levels and trimestral variation of triiodothyronine and thyroxine and their association with mortality in maintenance hemodialysis patients. Clin J Am Soc Nephrol 2012;7(1):131-8. [Pubmed]
[46]
Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med 2001;344(7):501-9. [Pubmed]
[47]
Trivieri MG, Oudit GY, Sah R, Kerfant BG, Sun H, Gramolini AO, et al. Cardiac-specific elevations in thyroid hormone enhance contractility and prevent pressure overload-induced cardiac dysfunction. Proc Natl Acad Sci U S A 2006;103(15):6043-8. [Pubmed]
[48]
Büssemaker E, Popp R, Fisslthaler B, Larson CM, Fleming I, Busse R, et al. Hyperthyroidism enchances endothelium-dependent relaxation in the rat renal artery. Cardiovasc Res 2003;59(1):181-8. [Pubmed]
[49]
Ozen KP, Asci G, Gungor O, Carrero JJ, Kircelli F, Tatar E, et al. Nutritional state alters the association between free triiodothyronine levels and mortality in hemodialysis patients. Am J Nephrol 2011;33(4):305-12. [Pubmed]
[50]
Zoccali C, Benedetto F, Mallamaci F, Tripepi G, Cutrupi S, Pizzini P, et al. Low triiodothyronine and cardiomyopathy in patients with end-stage renal disease. J Hypertens 2006;24(10):2039-46. [Pubmed]
[51]
Gerdes AM, Iervasi G. Thyroid replacement therapy and heart failure. Circulation 2010;122(4):385-93. [Pubmed]
[52]
Pingitore A, Galli E, Barison A, Iervasi A, Scarlattini M, Nucci D, et al. Acute effects of triiodothyronine (T3) replacement therapy in patients with chronic heart failure and low-T3 syndrome: a randomized, placebo-controlled study. J Clin Endocrinol Metab 2008;93:1351-8. [Pubmed]
