Renal protection by sodium-glucose cotransporter 2 inhibitors and its underlying mechanisms in diabetic kidney disease

Journal of Diabetes and its Complications

Volumn 32, Issue 7, 2018, Pages 720-725

  Mima, Akira ^a  

^a KINDAI UNIVERSITY NARA HOSPITAL   (Japan)

Author keywords

Diabetic kidney disease (DKD); Erythropoietin; Glucagon like peptide 1 (GLP 1); Ketosis; Sodium glucose cotransporter 2 (SGLT2) inhibitors; Type 2 diabetes

Indexed keywords

CREATININE; EMPAGLIFLOZIN; ERYTHROPOIETIN; INCRETIN; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; ANTIDIABETIC AGENT; SLC5A2 PROTEIN, HUMAN; SODIUM GLUCOSE COTRANSPORTER 2;

ALBUMINURIA; ANTIINFLAMMATORY ACTIVITY; BODY WEIGHT LOSS; CLINICAL OUTCOME; CREATININE BLOOD LEVEL; DIABETIC NEPHROPATHY; DISEASE EXACERBATION; DIURESIS; DRUG EFFECT; DRUG MECHANISM; ENDOTHELIUM; GLOMERULUS FILTRATION RATE; GLYCEMIC CONTROL; HEART FAILURE; HUMAN; HYPERTENSION; KETOACIDOSIS; KIDNEY FUNCTION; NERVE CONDUCTION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; RENAL PROTECTION; RENAL REPLACEMENT THERAPY; REVIEW; RISK REDUCTION; SYMPATHETIC NERVE; CELL PROTECTION; COMPLICATION; DIABETIC KETOACIDOSIS; KIDNEY; PATHOLOGY; PATHOPHYSIOLOGY; PHARMACOLOGY; PHYSIOLOGY; SIGNAL TRANSDUCTION;

CYTOPROTECTION; DIABETES MELLITUS, TYPE 2; DIABETIC KETOACIDOSIS; DIABETIC NEPHROPATHIES; DISEASE PROGRESSION; HUMANS; HYPOGLYCEMIC AGENTS; KIDNEY; SIGNAL TRANSDUCTION; SODIUM-GLUCOSE TRANSPORTER 2; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS;

EID: 85047881315     PISSN: 10568727     EISSN: 1873460X     Source Type: Journal    
DOI: 10.1016/j.jdiacomp.2018.04.011     Document Type: Review

References (92)

1. Diabetes C, Complications Trial Research G, Nathan, D.M. et al., The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329 (1993), 977–986.
2. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet, 352, 1998, 837–853.
3. Liu, J.J., Lee, T., DeFronzo, R.A., Why do SGLT2 inhibitors inhibit only 30–50% of renal glucose reabsorption in humans?. Diabetes 61 (2012), 2199–2204.
4. Rahmoune, H., Thompson, P.W., Ward, J.M., Smith, C.D., Hong, G., Brown, J., Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 54 (2005), 3427–3434.
5. Abdul-Ghani, M.A., DeFronzo, R.A., Norton, L., Novel hypothesis to explain why SGLT2 inhibitors inhibit only 30–50% of filtered glucose load in humans. Diabetes 62 (2013), 3324–3328.
6. Ito, D., Shimizu, S., Inoue, K. et al., Comparison of ipragliflozin and pioglitazone effects on nonalcoholic fatty liver disease in patients with type 2 diabetes: a randomized, 24-week, open-label, active-controlled trial. Diabetes Care 40 (2017), 1364–1372.
7. List, J.F., Woo, V., Morales, E., Tang, W., Fiedorek, F.T., Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 32 (2009), 650–657.
8. Bolinder, J., Ljunggren, O., Johansson, L. et al., Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab 16 (2014), 159–169.
9. Wanner, C., Inzucchi, S.E., Zinman, B., Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375 (2016), 1801–1802.
10. Neal, B., Perkovic, V., Matthews, D.R., Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med, 377, 2017, 2099.
11. Roden, M., Weng, J., Eilbracht, J. et al., Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol 1 (2013), 208–219.
12. Cefalu, W.T., Leiter, L.A., Yoon, K.H. et al., Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382 (2013), 941–950.
13. Fioretto, P., Steffes, M.W., Sutherland, D.E., Goetz, F.C., Mauer, M., Reversal of lesions of diabetic nephropathy after pancreas transplantation. N Engl J Med 339 (1998), 69–75.
14. Coca, S.G., Ismail-Beigi, F., Haq, N., Krumholz, H.M., Parikh, C.R., Role of intensive glucose control in development of renal end points in type 2 diabetes mellitus: systematic review and meta-analysis intensive glucose control in type 2 diabetes. Arch Intern Med 172 (2012), 761–769.
15. Brenner, B.M., Hemodynamically mediated glomerular injury and the progressive nature of kidney disease. Kidney Int 23 (1983), 647–655.
16. Hayashi, K., Epstein, M., Loutzenhiser, R., Forster, H., Impaired myogenic responsiveness of the afferent arteriole in streptozotocin-induced diabetic rats: role of eicosanoid derangements. J Am Soc Nephrol 2 (1992), 1578–1586.
17. Lewis, E.J., Hunsicker, L.G., Bain, R.P., Rohde, R.D., The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 329 (1993), 1456–1462.
18. Brenner, B.M., Cooper, M.E., de Zeeuw, D. et al., Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 345 (2001), 861–869.
19. Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet, 349, 1997, 1857–1863.
20. Mima, A., Hiraoka-Yamomoto, J., Li, Q. et al., Protective effects of GLP-1 on glomerular endothelium and its inhibition by PKCbeta activation in diabetes. Diabetes 61 (2012), 2967–2979.
21. Bakris, G.L., Weir, M.R., Angiotensin-converting enzyme inhibitor-associated elevations in serum creatinine: is this a cause for concern?. Arch Intern Med 160 (2000), 685–693.
22. Holtkamp, F.A., de Zeeuw, D., Thomas, M.C. et al., An acute fall in estimated glomerular filtration rate during treatment with losartan predicts a slower decrease in long-term renal function. Kidney Int 80 (2011), 282–287.
23. Fried, L.F., Emanuele, N., Zhang, J.H. et al., Combined angiotensin inhibition for the treatment of diabetic nephropathy. N Engl J Med 369 (2013), 1892–1903.
24. Vallon, V., Richter, K., Blantz, R.C., Thomson, S., Osswald, H., Glomerular hyperfiltration in experimental diabetes mellitus: potential role of tubular reabsorption. J Am Soc Nephrol 10 (1999), 2569–2576.
25. Musso, G., Gambino, R., Cassader, M., Pagano, G., A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials. Ann Med 44 (2012), 375–393.
26. Stanton, R.C., Sodium glucose transport 2 (SGLT2) inhibition decreases glomerular hyperfiltration: is there a role for SGLT2 inhibitors in diabetic kidney disease?. Circulation 129 (2014), 542–544.
27. Cherney, D.Z., Perkins, B.A., Soleymanlou, N. et al., The effect of empagliflozin on arterial stiffness and heart rate variability in subjects with uncomplicated type 1 diabetes mellitus. Cardiovasc Diabetol, 13, 2014, 28.
28. Perkins, B.A., Cherney, D.Z., Partridge, H. et al., Sodium-glucose cotransporter 2 inhibition and glycemic control in type 1 diabetes: results of an 8-week open-label proof-of-concept trial. Diabetes Care 37 (2014), 1480–1483.
29. Skrtic, M., Yang, G.K., Perkins, B.A. et al., Characterisation of glomerular haemodynamic responses to SGLT2 inhibition in patients with type 1 diabetes and renal hyperfiltration. Diabetologia 57 (2014), 2599–2602.
30. Kimura, G., Importance of inhibiting sodium-glucose cotransporter and its compelling indication in type 2 diabetes: pathophysiological hypothesis. J Am Soc Hypertens 10 (2016), 271–278.
31. Lin, B., Koibuchi, N., Hasegawa, Y. et al., Glycemic control with empagliflozin, a novel selective SGLT2 inhibitor, ameliorates cardiovascular injury and cognitive dysfunction in obese and type 2 diabetic mice. Cardiovasc Diabetol, 13, 2014, 148.
32. Kimura, G., Diuretic action of sodium-glucose cotransporter 2 inhibitors and its importance in the management of heart failure. Circ J 80 (2016), 2277–2281.
33. Greger, R., Velazquez, H., The cortical thick ascending limb and early distal convoluted tubule in the urinary concentrating mechanism. Kidney Int 31 (1987), 590–596.
34. Pessoa, T.D., Campos, L.C., Carraro-Lacroix, L., Girardi, A.C., Malnic, G., Functional role of glucose metabolism, osmotic stress, and sodium-glucose cotransporter isoform-mediated transport on Na+/H+ exchanger isoform 3 activity in the renal proximal tubule. J Am Soc Nephrol 25 (2014), 2028–2039.
35. Mima, A., Diabetic nephropathy: protective factors and a new therapeutic paradigm. J Diabetes Complications 27 (2013), 526–530.
36. Mima, A., Inflammation and oxidative stress in diabetic nephropathy: new insights on its inhibition as new therapeutic targets. J Diabetes Res, 2013, 2013, 248563.
37. Ohshiro, Y., Ma, R.C., Yasuda, Y. et al., Reduction of diabetes-induced oxidative stress, fibrotic cytokine expression, and renal dysfunction in protein kinase Cbeta-null mice. Diabetes 55 (2006), 3112–3120.
38. Kanamori, H., Matsubara, T., Mima, A. et al., Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy. Biochem Biophys Res Commun 360 (2007), 772–777.
39. Li, Q., Park, K., Li, C. et al., Induction of vascular insulin resistance and endothelin-1 expression and acceleration of atherosclerosis by the overexpression of protein kinase C-beta isoform in the endothelium. Circ Res 113 (2013), 418–427.
40. Abiko, T., Abiko, A., Clermont, A.C. et al., Characterization of retinal leukostasis and hemodynamics in insulin resistance and diabetes: role of oxidants and protein kinase-C activation. Diabetes 52 (2003), 829–837.
41. Durpes, M.C., Morin, C., Paquin-Veillet, J. et al., PKC-beta activation inhibits IL-18-binding protein causing endothelial dysfunction and diabetic atherosclerosis. Cardiovasc Res 106 (2015), 303–313.
42. Geraldes, P., Hiraoka-Yamamoto, J., Matsumoto, M. et al., Activation of PKC-delta and SHP-1 by hyperglycemia causes vascular cell apoptosis and diabetic retinopathy. Nat Med 15 (2009), 1298–1306.
43. Mima, A., Kitada, M., Geraldes, P. et al., Glomerular VEGF resistance induced by PKCdelta/SHP-1 activation and contribution to diabetic nephropathy. FASEB J 26 (2012), 2963–2974.
44. Gohda, T., Niewczas, M.A., Ficociello, L.H. et al., Circulating TNF receptors 1 and 2 predict stage 3 CKD in type 1 diabetes. J Am Soc Nephrol 23 (2012), 516–524.
45. Gohda, T., Maruyama, S., Kamei, N. et al., Circulating TNF receptors 1 and 2 predict mortality in patients with end-stage renal disease undergoing Dialysis. Sci Rep, 7, 2017, 43520.
46. Mima, A., Yasuzawa, T., King, G.L., Ueshima, S., Obesity-associated glomerular inflammation increases albuminuria without renal histological changes. FEBS Open Bio 8 (2018), 664–670.
47. Gallo, L.A., Ward, M.S., Fotheringham, A.K. et al., Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice. Sci Rep, 6, 2016, 26428.
48. Pugliese, G., Pricci, F., Iacobini, C. et al., Accelerated diabetic glomerulopathy in galectin-3/AGE receptor 3 knockout mice. FASEB J 15 (2001), 2471–2479.
49. Forbes, J.M., Thallas, V., Thomas, M.C. et al., The breakdown of preexisting advanced glycation end products is associated with reduced renal fibrosis in experimental diabetes. FASEB J 17 (2003), 1762–1764.
50. Cooper, M.E., Importance of advanced glycation end products in diabetes-associated cardiovascular and renal disease. Am J Hypertens 17 (2004), 31S–38S.
51. Oelze, M., Kroller-Schon, S., Welschof, P. et al., The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity. PLoS One, 9, 2014, e112394.
52. Ojima, A., Matsui, T., Nishino, Y., Nakamura, N., Yamagishi, S., Empagliflozin, an inhibitor of sodium-glucose cotransporter 2 exerts anti-inflammatory and antifibrotic effects on experimental diabetic nephropathy partly by suppressing AGEs-receptor axis. Horm Metab Res 47 (2015), 686–692.
53. Mima, A., Ohshiro, Y., Kitada, M. et al., Glomerular-specific protein kinase C-beta-induced insulin receptor substrate-1 dysfunction and insulin resistance in rat models of diabetes and obesity. Kidney Int 79 (2011), 883–896.
54. Park, K., Mima, A., Li, Q. et al., Insulin decreases atherosclerosis by inducing endothelin receptor B expression. JCI Insight, 1, 2016.
55. Salim, H.M., Fukuda, D., Yagi, S., Soeki, T., Shimabukuro, M., Sata, M., Glycemic control with Ipragliflozin, a novel selective SGLT2 inhibitor, ameliorated endothelial dysfunction in Streptozotocin-induced diabetic mouse. Front Cardiovasc Med, 3, 2016, 43.
56. Julius, S., Jamerson, K., Sympathetics, insulin resistance and coronary risk in hypertension: the ‘chicken-and-egg’ question. J Hypertens 12 (1994), 495–502.
57. Brotman, D.J., Bash, L.D., Qayyum, R. et al., Heart rate variability predicts ESRD and CKD-related hospitalization. J Am Soc Nephrol 21 (2010), 1560–1570.
58. Pestell, R.G., Kirsner, R.L., Best, J.D., Validation and evaluation of test for sympathetic cholinergic function in diabetes mellitus. Diabetes 40 (1991), 867–872.
59. Morgan, D.A., Anderson, E.A., Mark, A.L., Renal sympathetic nerve activity is increased in obese Zucker rats. Hypertension 25 (1995), 834–838.
60. Kobayashi, S., Ikeda, T., Moriya, H., Ohtake, T., Kumagai, H., Asymptomatic cerebral lacunae in patients with chronic kidney disease. Am J Kidney Dis 44 (2004), 35–41.
61. Ohtomo, Y., Meister, B., Hokfelt, T., Aperia, A., Coexisting NPY and NE synergistically regulate renal tubular Na+, K(+)-ATPase activity. Kidney Int 45 (1994), 1606–1613.
62. Masuo, K., Rakugi, H., Ogihara, T., Esler, M.D., Lambert, G.W., Cardiovascular and renal complications of type 2 diabetes in obesity: role of sympathetic nerve activity and insulin resistance. Curr Diabetes Rev 6 (2010), 58–67.
63. Vazir, A., Claggett, B., Pitt, B. et al., Prognostic importance of temporal changes in resting heart rate in heart failure and preserved ejection fraction: from the TOPCAT study. JACC. Heart Fail 5 (2017), 782–791.
64. Bhatt, D.L., Bakris, G.L., Renal denervation for resistant hypertension. N Engl J Med, 371, 2014, 184.
65. Rahman, A., Hitomi, H., Nishiyama, A., Cardioprotective effects of SGLT2 inhibitors are possibly associated with normalization of the circadian rhythm of blood pressure. Hypertens Res 40 (2017), 535–540.
66. Matthews, V.B., Elliot, R.H., Rudnicka, C., Hricova, J., Herat, L., Schlaich, M.P., Role of the sympathetic nervous system in regulation of the sodium glucose cotransporter 2. J Hypertens 35 (2017), 2059–2068.
67. Sano, M., Hemodynamic effects of sodium-glucose cotransporter 2 inhibitors. J Clin Med Res 9 (2017), 457–460.
68. Kiuchi, S., Hisatake, S., Kabuki, T. et al., Long-term use of ipragliflozin improved cardiac sympathetic nerve activity in a patient with heart failure: a case report. Drug Discov Ther 12 (2018), 51–54.
69. Rafiq, K., Fujisawa, Y., Sherajee, S.J. et al., Role of the renal sympathetic nerve in renal glucose metabolism during the development of type 2 diabetes in rats. Diabetologia 58 (2015), 2885–2898.
70. Mann, J.F.E., Orsted, D.D., Brown-Frandsen, K. et al., Liraglutide and renal outcomes in type 2 diabetes. N Engl J Med 377 (2017), 839–848.
71. Kanasaki, K., Shi, S., Kanasaki, M. et al., Linagliptin-mediated DPP-4 inhibition ameliorates kidney fibrosis in streptozotocin-induced diabetic mice by inhibiting endothelial-to-mesenchymal transition in a therapeutic regimen. Diabetes 63 (2014), 2120–2131.
72. Shi, S., Srivastava, S.P., Kanasaki, M. et al., Interactions of DPP-4 and integrin beta1 influences endothelial-to-mesenchymal transition. Kidney Int 88 (2015), 479–489.
73. Zambrowicz, B., Ding, Z.M., Ogbaa, I. et al., Effects of LX4211, a dual SGLT1/SGLT2 inhibitor, plus sitagliptin on postprandial active GLP-1 and glycemic control in type 2 diabetes. Clin Ther 35 (2013), 273–285.e277.
74. Oguma, T., Nakayama, K., Kuriyama, C. et al., Intestinal sodium glucose cotransporter 1 inhibition enhances glucagon-like Peptide-1 secretion in normal and diabetic rodents. J Pharmacol Exp Ther 354 (2015), 279–289.
75. Oguma, T., Kuriyama, C., Nakayama, K. et al., The effect of combined treatment with canagliflozin and teneligliptin on glucose intolerance in Zucker diabetic fatty rats. J Pharmacol Sci 127 (2015), 456–461.
76. Williams, D.M., Stephens, J.W., Combination therapy with saxagliptin and dapagliflozin for the treatment of type 2 diabetes. Expert Opin Pharmacother 16 (2015), 2373–2379.
77. Rajeev, S.P., Cuthbertson, D.J., Wilding, J.P., Energy balance and metabolic changes with sodium-glucose co-transporter 2 inhibition. Diabetes Obes Metab 18 (2016), 125–134.
78. Ferrannini, E., Mark, M., Mayoux, E., CV protection in the EMPA-REG OUTCOME trial: A “thrifty substrate” hypothesis. Diabetes Care 39 (2016), 1108–1114.
79. Zinman, B., Wanner, C., Lachin, J.M. et al., Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 373 (2015), 2117–2128.
80. Mudaliar, S., Alloju, S., Henry, R.R., Can a shift in fuel energetics explain the beneficial cardiorenal outcomes in the EMPA-REG OUTCOME study? A unifying hypothesis. Diabetes Care 39 (2016), 1115–1122.
81. Gambhir, D., Ananth, S., Veeranan-Karmegam, R. et al., GPR109A as an anti-inflammatory receptor in retinal pigment epithelial cells and its relevance to diabetic retinopathy. Invest Ophthalmol Vis Sci 53 (2012), 2208–2217.
82. Shimazu, T., Hirschey, M.D., Newman, J. et al., Suppression of oxidative stress by beta-hydroxybutyrate, an endogenous histone deacetylase inhibitor. Science 339 (2013), 211–214.
83. Lambers Heerspink, H.J., de Zeeuw, D., Wie, L., Leslie, B., List, J., Dapagliflozin a glucose-regulating drug with diuretic properties in subjects with type 2 diabetes. Diabetes Obes Metab 15 (2013), 853–862.
84. Evans, R.G., Ince, C., Joles, J.A. et al., Haemodynamic influences on kidney oxygenation: clinical implications of integrative physiology. Clin Exp Pharmacol Physiol 40 (2013), 106–122.
85. O'Neill, J., Fasching, A., Pihl, L., Patinha, D., Franzen, S., Palm, F., Acute SGLT inhibition normalizes O2 tension in the renal cortex but causes hypoxia in the renal medulla in anaesthetized control and diabetic rats. Am J Physiol Renal Physiol 309 (2015), F227–F234.
86. Zeisberg, M., Kalluri, R., Physiology of the renal interstitium. Clin J Am Soc Nephrol 10 (2015), 1831–1840.
87. Ishihara, M., Urushido, M., Hamada, K. et al., Sestrin-2 and BNIP3 regulate autophagy and mitophagy in renal tubular cells in acute kidney injury. Am J Physiol Renal Physiol 305 (2013), F495–F509.
88. Silagi, E.S., Schoepflin, Z.R., Seifert, E.L. et al., Bicarbonate recycling by HIF-1-dependent carbonic anhydrase isoforms 9 and 12 is critical in maintaining intracellular pH and viability of nucleus pulposus cells. J Bone Miner Res 33 (2018), 338–355.
89. Miyata, T., Suzuki, N., Vvan Ypersele de Strihou, C., Diabetic nephropathy: are there new and potentially promising therapies targeting oxygen biology?. Kidney Int 84 (2013), 693–702.
90. Kishi, S., Abe, H., Akiyama, H. et al., SOX9 protein induces a chondrogenic phenotype of mesangial cells and contributes to advanced diabetic nephropathy. J Biol Chem 286 (2011), 32162–32169.
91. Asada, N., Takase, M., Nakamura, J. et al., Dysfunction of fibroblasts of extrarenal origin underlies renal fibrosis and renal anemia in mice. J Clin Invest 121 (2011), 3981–3990.
92. Sano, M., A new class of drugs for heart failure: SGLT2 inhibitors reduce sympathetic overactivity. J Cardiol 71 (2018), 471–476.