Efectos renales y nefroprotección inducidos por el inhibidor del SGLT2 Empagliflozina en pacientes con diabetes mellitus: revisión de la literatura

Contenido principal del artículo

Luis E. Morales-Buenrostro
Sonia Citlali Juárez-Comboni
Alma Nelly Rodríguez Alcocer

Resumen

La insuficiencia renal es una comorbilidad frecuente en pacientes con diabetes mellitus (DM) e incrementa en ellos el riesgo cardiovascular; la hiperglucemia crónica en pacientes con DM induce una gran cantidad de alteraciones directas e indirectas en la estructura y la función renal, y constituye el principal factor para el desarrollo de la nefropatía diabética y la enfermedad renal terminal. En la presente revisión, se exponen los resultados de los estudios en los que se ha demostrado la alta tolerabilidad de empagliflozina en pacientes diabéticos con insuficiencia renal
concomitante en estadios I a III. Empagliflozina, mediante la inhibición de SGLT2, ofrece una terapia novedosa con efectos benéficos no sólo sobre el control glucémico, sino también beneficios cardiovasculares y renales, los cuales han sido demostrados en el estudio EMPA-REG OUTCOME y continúan en evaluación en otros estudios.

Detalles del artículo

Cómo citar
1.
Morales-Buenrostro LE, Citlali Juárez-Comboni S, Rodríguez Alcocer AN. Efectos renales y nefroprotección inducidos por el inhibidor del SGLT2 Empagliflozina en pacientes con diabetes mellitus: revisión de la literatura. Rev Nefrol Dial Traspl. [Internet]. 1 de enero de 2017 [citado 3 de marzo de 2021];37(1):48-1. Disponible en: http://www.revistarenal.org.ar/index.php/rndt/article/view/89
Sección
Artículo de Revisión

Citas

1) Pálsson R, Patel UD. Cardiovascular complications of diabetic kidney disease. Adv Chronic Kidney Dis. 2014;21(3):273-80.

2) Levey AS, Eckardt KU, Tsukamoto Y, Levin A, Coresh J, Rossert J, et al. Definition and classification of chronic kidney disease: a position
statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int. 2005;67(6):2089-100.

3) Martínez-Castelao A, Navarro-González JF, Górriz JL, de Alvaro F. The Concept and the Epidemiology of Diabetic Nephropathy Have Changed in Recent Years. J Clin Med. 2015;4(6):1207-16.

4) Regele F, Jelencsics K, Shiffman D, Paré G, McQueen MJ, Mann JF, et al. Genome-wide studies to identify risk factors for kidney disease with a
focus on patients with diabetes. Nephrol Dial Transplant. 2015;30 Suppl 4:iv26-34.

5) Lambers Heerspink HJ, Oberbauer R, Perco P, Heinzel A, Heinze G, Mayer G, et al. Drugs meeting the molecular basis of diabetic kidney disease: bridging from molecular mechanism to personalized medicine. Nephrol Dial Transplant. 2015;30(suppl 4):iv105-12.

6) Slyne J, Slattery C, McMorrow T, Ryan MP. New developments concerning the proximal tubule in diabetic nephropathy: in vitro models and mechanisms. Nephrol Dial Transplant. 2015;30 Suppl 4:iv60-7.

7) Zoja C, Zanchi C, Benigni A. Key pathways in renal disease progression of experimental diabetes. Nephrol Dial Transplant. 2015;30 Suppl 4:iv54-9.

8) Rosas Guzmán J, García Rubí E, Gómez Pérez FJ, Calles J, Barceló A, García G, et al. Prevención, diagnóstico y tratamiento temprano de la
nefropatía diabética. Rev ALAD 2009;17(3):106-14.

9) Carranza K, Veron D, Cercado A, Bautista N, Pozo W, Tufro A, et al. Cellular and molecular aspects of diabetic nephropathy; the role of VEGF-A. Nefrologia. 2015;35(2):131-8.

10) De Nicola L, Gabbai FB, Liberti ME, Sagliocca A, Conte G, Minutolo R. Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic
nephropathy: targeting the renal tubule in diabetes. Am J Kidney Dis. 2014;64(1):16-24.

11) Cherney DZ, Perkins BA, Soleymanlou N, Maione M, Lai V, Lee A, et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation. 2014;129(5):587-97.

12) Marshall S. Recent advances in diabetic nephropathy. Postgrad Med J. 2004;80(949):624-33.

13) Nakagawa T, Tanabe K, Croker BP, Johnson RJ, Grant MB, Kosugi T, et al. Endothelial dysfunction as a potential contributor in diabetic nephropathy. Nat Rev Nephrol. 2011;7(1):36-44.

14) Riser BL, Varani J, Cortes P, Yee J, Dame M, Sharba AK. Cyclic stretching of mesangial cells up-regulates intercellular adhesion molecule-1 and leukocyte adherence: a possible new mechanism for glomerulosclerosis. Am J Pathol. 2001;158(1):11-7.

15) Reidy K, Kang HM, Hostetter T, Susztak K. Molecular mechanisms of diabetic kidney disease. J Clin Invest. 2014;124(6):2333-40.

16) Rodríguez-Iturbe B, Johnson RJ, Herrera-Acosta J. Tubulointerstitial damage and progression of renal failure. Kidney Int Suppl. 2005;68(Suppl 99):S82-6.

17) Rodríguez-Iturbe B, Vaziri ND, Herrera-Acosta J, Johnson RJ. Oxidative stress renal infiltration of immune cells, and salt-sensitive
hypertension: all for one and one for all. Am J Physiol Renal Physiol. 2004;286(4):F606-16.

18) Sánchez-Lozada LG, Tapia E, Johnson RJ, Rodríguez-Iturbe B, Herrera-Acosta J. Glomerular hemodynamic changes associated with arteriolar lesions and tubulointerstitial inflammation. Kidney Int Suppl. 2003;64(Suppl 86):S9-14.

19) National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J
Kidney Dis. 2002;39(2 Suppl 1):S1-266.

20) Chapter 2: Definition, identification, and prediction of CKD progression. Kidney Int Suppl (2011). 2013;3(1):63-72.

21) Haneda M, Utsunomiya K, Koya D, Babazono T, Moriya T, Makino H, et al. A new classification of Diabetic Nephropathy 2014: a report from Joint Committee on Diabetic Nephropathy. Clin Exp Nephrol. 2015;19(1):1-5.

22) Macía Heras M, Macía Jerez M, Coronel F. Diabetic nephropathy: physiopathology and clinical course. Nefrologia. 2001;21 Suppl 3:24-31.

23) Neumiller JJ. Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. Drugs Context. 2014;3:212262.

24) Gerich JE. Role of the kidney in normal glucose homeostasis and in the hyperglycaemia of diabetes mellitus: therapeutic implications. Diabet Med. 2010;27(2):136-42.

25) Heise T, Seman L, Macha S, Jones P, Marquart A, Pinnetti S, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple rising doses of empagliflozin in patients with type 2 diabetes mellitus. Diabetes Ther. 2013;4(2):331-45.

26) Kanada S, Koiwai K, Taniguchi A, Sarashina A, Seman L, Woerle HJ. Pharmacokinetics, pharmacodynamics, safety and tolerability of 4 weeks'
treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus. J Diabetes Investig. 2013;4(6):613-7.

27) Hansen HH, Jelsing J, Hansen CF, Hansen G, Vrang N, Mark M, et al. The sodium glucose cotransporter type 2 inhibitor empagliflozin preserves β-cell mass and restores glucose homeostasis in the male zucker diabetic fatty rat. J Pharmacol Exp Ther. 2014;350(3):657-64.

28) Solini A. Extra-glycaemic properties of empagliflozin. Diabetes Metab Res Rev. 2016;32(3):230-7.

29) Ferrannini E, Muscelli E, Frascerra S, Baldi S, Mari A, Heise T, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type
2 diabetic patients. J Clin Invest. 2014; 124(2):499-508.

30) Cherney DZ, Perkins BA, Soleymanlou N, Har R, Fagan N, Johansen OE, et al. The effect of empagliflozin on arterial stiffness and heart rate
variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc Diabetol. 2014;13:28.

31) Ring A, Brand T, Macha S, Breithaupt-Groegler K, Simons G, Walter B, et al. The sodium glucose cotransporter 2 inhibitor empagliflozin does not prolong QT interval in a thorough QT (TQT) study. Cardiovasc Diabetol. 2013;12:70.

32) Zinman B, Inzucchi SE, Lachin JM, Wanner C, Ferrari R, Fitchett D, et al. Rationale, design, and baseline characteristics of a randomized,
placebo-controlled cardiovascular outcome trial of empagliflozin (EMPA-REG OUTCOME™). Cardiovasc Diabetol. 2014;13:102.

33) Zinman B, Lachin JM, Inzucchi SE. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2016;374(11):1094.

34) Sattar N, McLaren J, Kristensen SL, Preiss D, McMurray JJ. SGLT2 Inhibition and cardiovascular events: why did EMPA-REG Outcomes surprise and what were the likely mechanisms? Diabetologia. 2016;59(7):1333-9.

35) Ferrannini E, Mark M, Mayoux E. CV Protection in the EMPA-REG OUTCOME Trial: A "Thrifty Substrate" Hypothesis. Diabetes Care. 2016;39(7):1108-14.

36) Pérez López G, González Albarrán O, Cano Megías M. Sodium-glucose cotransporter type 2 inhibitors (SGLT2): from familial renal glucosuria to the treatment of type 2 diabetes mellitus. Nefrologia. 2010;30(6):618-25.

37) Santer R, Calado J. Familial renal glucosuria and SGLT2: from a mendelian trait to a therapeutic target. Clin J Am Soc Nephrol. 2010;5(1):133-41.

38) Scheen AJ. Pharmacokinetic and pharmacodynamic profile of empagliflozin, a sodium glucose co-transporter 2 inhibitor. Clin Pharmacokinet. 2014;53(3):213-25.

39) Vivian EM. Sodium-glucose co-transporter 2 (SGLT2) inhibitors: a growing class of antidiabetic agents. Drugs Context. 2014;3:212264.

40) Nauck MA. Update on developments with SGLT2 inhibitors in the management of type 2 diabetes. Drug Des Devel Ther. 2014;8:1335-80.

41) Gembardt F, Bartaun C, Jarzebska N, Mayoux E, Todorov VT, Hohenstein B. The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension. Am J Physiol Renal Physiol. 2014;307(3):F317-25.

42) Cherney D, Lund SS, Perkins BA, Groop PH, Cooper ME, Kaspers S, et al. The effect of sodium glucose cotransporter 2 inhibition with
empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes. Diabetologia. 2016;59(9):1860-70.

43) Wanner C, Inzucchi SE, Lachin JM, Fitchett D, von Eynatten M, Mattheus M, et al. Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes. N Engl J Med. 2016;375(4):323-34.

44) Hinnen D. Short commentary on empagliflozin and its potential clinical impact. Ther Adv Endocrinol Metab. 2015;6(2):68-81.

45) Rosenwasser RF, Sultan S, Sutton D, Choksi R, Epstein BJ. SGLT-2 inhibitors and their potential in the treatment of diabetes. Diabetes Metab
Syndr Obes. 2013;6:453-67.

46) DeFronzo RA, Norton L, Abdul-Ghani M. Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat Rev Nephrol. 2017;13(1):11-26.

47) Goldenberg RM, Berard LD, Cheng AY, Gilbert JD, Verma S, Woo VC, et al. SGLT2 Inhibitor-associated Diabetic Ketoacidosis: Clinical Review and Recommendations for Prevention and Diagnosis. Clin Ther. 2016;38(12):2654-64.e1.