Diuretic effects of sodium glucose cotransporter 2 inhibitors and their influence on the renin-angiotensin system

International Journal of Molecular Sciences

Volumn 20, Issue 3, 2019, Pages

  Ansary, Tuba M ^a   Nakano, Daisuke ^a   Nishiyama, Akira ^a  

^a KAGAWA UNIVERSITY   (Japan)

Author keywords

Diuretic effect; Natriuresis; Renin angiotensin system (RAS); Sodium glucose cotransporter 2 (SGLT2) inhibitor; Type 2 diabetes

Indexed keywords

ALDOSTERONE; ANGIOTENSIN II; ANGIOTENSIN RECEPTOR ANTAGONIST; ANGIOTENSINOGEN; AQUAPORIN 2; CANAGLIFLOZIN; CREATININE; DAPAGLIFLOZIN; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; EMPAGLIFLOZIN; EPITHELIAL SODIUM CHANNEL; HEMOGLOBIN A1C; INSULIN; MESSENGER RNA; SODIUM CHLORIDE COTRANSPORTER; SODIUM GLUCOSE COTRANSPORTER 2 INHIBITOR; SODIUM POTASSIUM CHLORIDE COTRANSPORTER 2; SODIUM PROTON EXCHANGE PROTEIN 3; ANTIDIABETIC AGENT; DIURETIC AGENT; GLUCOSE; SLC5A2 PROTEIN, HUMAN; SODIUM GLUCOSE COTRANSPORTER 2;

ANTIHYPERTENSIVE ACTIVITY; CLINICAL TRIAL (TOPIC); DIURESIS; GLOMERULUS FILTRATION; GLOMERULUS FILTRATION RATE; GLUCOSE BLOOD LEVEL; GLUCOSURIA; HEART PROTECTION; HEMODYNAMICS; HUMAN; HYPERGLYCEMIA; HYPERTENSION; INSULIN DEPENDENT DIABETES MELLITUS; KIDNEY TUBULE FUNCTION; METABOLIC SYNDROME X; NATRIURESIS; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PLASMA RENIN ACTIVITY; POLYURIA; PROTEIN EXPRESSION; REGULATORY MECHANISM; RENIN ANGIOTENSIN ALDOSTERONE SYSTEM; REVIEW; SODIUM URINE LEVEL; URINE VOLUME; ADMINISTRATION AND DOSAGE; BLOOD PRESSURE; CHEMICALLY INDUCED; DRUG EFFECT; GENE EXPRESSION; GENETICS; METABOLISM; PATHOPHYSIOLOGY;

BLOOD PRESSURE; DIABETES MELLITUS, TYPE 2; DIURETICS; GENE EXPRESSION; GLUCOSE; GLYCOSURIA; HUMANS; HYPERGLYCEMIA; HYPERTENSION; HYPOGLYCEMIC AGENTS; NATRIURESIS; POLYURIA; RENIN-ANGIOTENSIN SYSTEM; SODIUM-GLUCOSE TRANSPORTER 2; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS;

EID: 85061139630     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms20030629     Document Type: Review

References (92)

1. Aguillón, A.R.; Mascarello, A.; Segretti, N.D.; de Azevedo, H.F.Z.; Guimaraes, C.R.W.; Miranda, L.S.M.; de Souza, R.O.M.A. Synthetic Strategies toward SGLT2 Inhibitors. Org. Process Res. Dev. 2018, 22, 467–488.
2. Hsia, D.S.; Grove, O.; Cefalu, W.T. An update on sodium-glucose co-transporter-2 inhibitors for the treatment of diabetes mellitus. Curr. Opin. Endocrinol. Diabetes Obes. 2017, 24, 73–79.
3. Tahara, A.; Takasu, T.; Yokono, M.; Imamura, M.; Kurosaki, E. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors: Part 2. Antidiabetic effects in type 2 diabetic mice. J. Pharmacol. Sci. 2016, 131, 198–208.
4. Ferrannini, E.; Solini, A. SGLT2 inhibition in diabetes mellitus: Rationale and clinical prospects. Nat. Rev. Endocrinol. 2012, 8, 495–502.
5. DeFronzo, R.A.; Davidson, J.A.; Del Prato, S. The role of the kidneys in glucose homeostasis: A new path towards normalizing glycaemia. Diabetes Obes. Metab. 2012, 14, 5–14.
6. Liu, J.J.; Lee, T.; DeFronzo, R.A. Why Do SGLT2 inhibitors inhibit only 30–50% of renal glucose reabsorption in humans? Diabetes 2012, 61, 2199–2204.
7. 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 2005, 54, 3427–3434.
8. 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 2013, 62, 3324–3328.
9. Vallon, V.; Platt, K.A.; Cunard, R.; Schroth, J.; Whaley, J.; Thomson, S.C.; Koepsell, H.; Rieg, T. SGLT2 mediates glucose reabsorption in the early proximal tubule. J. Am. Soc. Nephrol. 2011, 22, 104–112.
10. Rieg, T.; Masuda, T.; Gerasimova, M.; Mayoux, E.; Platt, K.; Powell, D.R.; Thomson, S.C.; Koepsell, H.; Vallon, V. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia. Am. J. Physiol. Ren. Physiol. 2014, 306, F188–F193.
11. Heerspink, H.J.; Perkins, B.A.; Fitchett, D.H.; Husain, M.; Cherney, D.Z. Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications. Circulation 2016, 134, 752–772.
12. Lytvyn, Y.; Skrtic, M.; Yang, G.K.; Yip, P.M.; Perkins, B.A.; Cherney, D.Z. Glycosuria-mediated urinary uric acid excretion in patients with uncomplicated type 1 diabetes mellitus. Am. J. Physiol. Ren. Physiol. 2015, 308, F77–F83.
13. Yamazaki, D.; Hitomi, H.; Nishiyama, A. Hypertension with diabetes mellitus complications. Hypertens. Res. 2018, 41, 147–156.
14. Zinman, B.; Wanner, C.; Lachin, J.M.; Fitchett, D.; Bluhmki, E.; Hantel, S.; Mattheus, M.; Devins, T.; Johansen, O.E.; Woerle, H.J.; et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N. Engl. J. Med. 2015, 373, 2117–2128.
15. Radholm, K.; Figtree, G.; Perkovic, V.; Solomon, S.D.; Mahaffey, K.W.; de Zeeuw, D.; Fulcher, G.; Barrett, T.D.; Shaw, W.; Desai, M.; et al. Canagliflozin and Heart Failure in Type 2 Diabetes Mellitus: Results From the CANVAS Program (Canagliflozin Cardiovascular Assessment Study). Circulation 2018.
16. Tanaka, H.; Takano, K.; Iijima, H.; Kubo, H.; Maruyama, N.; Hashimoto, T.; Arakawa, K.; Togo, M.; Inagaki, N.; Kaku, K. Factors Affecting Canagliflozin-Induced Transient Urine Volume Increase in Patients with Type 2 Diabetes Mellitus. Adv. Ther. 2017, 34, 436–451.
17. Rajasekeran, H.; Lytvyn, Y.; Cherney, D.Z. Sodium-glucose cotransporter 2 inhibition and cardiovascular risk reduction in patients with type 2 diabetes: The emerging role of natriuresis. Kidney Int. 2016, 89, 524–526.
18. Sha, S.; Polidori, D.; Heise, T.; Natarajan, J.; Farrell, K.; Wang, S.S.; Sica, D.; Rothenberg, P.; Plum-Morschel, L. Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus. Diabetes Obes. Metab. 2014, 16, 1087–1095.
19. Iijima, H.; Kifuji, T.; Maruyama, N.; Inagaki, N. Pharmacokinetics, Pharmacodynamics, and Safety of Canagliflozin in Japanese Patients with Type 2 Diabetes Mellitus. Adv. Ther. 2015, 32, 768–782.
20. Rahman, A.; Kittikulsuth, W.; Fujisawa, Y.; Sufiun, A.; Rafiq, K.; Hitomi, H.; Nakano, D.; Sohara, E.; Uchida, S.; Nishiyama, A. Effects of diuretics on sodium-dependent glucose cotransporter 2 inhibitor-induced changes in blood pressure in obese rats suffering from the metabolic syndrome. J. Hypertens. 2016, 34, 893–906.
21. Ansary, T.M.; Fujisawa, Y.; Rahman, A.; Nakano, D.; Hitomi, H.; Kobara, H.; Masaki, T.; Titze, J.M.; Kitada, K.; Nishiyama, A. Responses of renal hemodynamics and tubular functions to acute sodium-glucose cotransporter 2 inhibitor administration in non-diabetic anesthetized rats. Sci. Rep. 2017, 7, 9555.
22. Thomson, S.C.; Rieg, T.; Miracle, C.; Mansoury, H.; Whaley, J.; Vallon, V.; Singh, P. Acute and chronic effects of SGLT2 blockade on glomerular and tubular function in the early diabetic rat. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2012, 302, R75–R83.
23. Takeshige, Y.; Fujisawa, Y.; Rahman, A.; Kittikulsuth, W.; Nakano, D.; Mori, H.; Masaki, T.; Ohmori, K.; Kohno, M.; Ogata, H.; et al. A sodium-glucose co-transporter 2 inhibitor empagliflozin prevents abnormality of circadian rhythm of blood pressure in salt-treated obese rats. Hypertens. Res. 2016, 39, 415–422.
24. Ferrannini, E.; Baldi, S.; Frascerra, S.; Astiarraga, B.; Barsotti, E.; Clerico, A.; Muscelli, E. Renal Handling of Ketones in Response to Sodium-Glucose Cotransporter 2 Inhibition in Patients With Type 2 Diabetes. Diabetes Care 2017, 40, 771–776.
25. 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. 2013, 15, 853–862.
26. Reed, J.W. Impact of sodium-glucose cotransporter 2 inhibitors on blood pressure. Vasc. Health Risk Manag. 2016, 12, 393–405.
27. Verma, S.; McMurray, J.J.V. SGLT2 inhibitors and mechanisms of cardiovascular benefit: A state-of-the-art review. Diabetologia 2018, 61, 2108–2117.
28. Lytvyn, Y.; Bjornstad, P.; Udell, J.A.; Lovshin, J.A.; Cherney, D.Z.I. Sodium Glucose Cotransporter-2 Inhibition in Heart Failure: Potential Mechanisms, Clinical Applications, and Summary of Clinical Trials. Circulation 2017, 136, 1643–1658.
29. Titze, J. A different view on sodium balance. Curr. Opin. Nephrol. Hypertens. 2015, 24, 14–20.
30. Schneider, M.P.; Raff, U.; Kopp, C.; Scheppach, J.B.; Toncar, S.; Wanner, C.; Schlieper, G.; Saritas, T.; Floege, J.; Schmid, M.; et al. Skin Sodium Concentration Correlates with Left Ventricular Hypertrophy in CKD. J. Am. Soc. Nephrol. 2017, 28, 1867–1876.
31. Karg, M.V.; Bosch, A.; Kannenkeril, D.; Striepe, K.; Ott, C.; Schneider, M.P.; Boemke-Zelch, F.; Linz, P.; Nagel, A.M.; Titze, J.; et al. SGLT-2-inhibition with dapagliflozin reduces tissue sodium content: A randomised controlled trial. Cardiovasc. Diabetol. 2018, 17, 5.
32. Heise, T.; Seewaldt-Becker, E.; Macha, S.; Hantel, S.; Pinnetti, S.; Seman, L.; Woerle, H.J. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks’ treatment with empagliflozin once daily in patients with type 2 diabetes. Diabetes Obes. Metab. 2013, 15, 613–621.
33. Weir, M.R.; Januszewicz, A.; Gilbert, R.E.; Vijapurkar, U.; Kline, I.; Fung, A.; Meininger, G. Effect of canagliflozin on blood pressure and adverse events related to osmotic diuresis and reduced intravascular volume in patients with type 2 diabetes mellitus. J. Clin. Hypertens. (Greenwich) 2014, 16, 875–882.
34. Bode, B.; Stenlof, K.; Sullivan, D.; Fung, A.; Usiskin, K. Efficacy and safety of canagliflozin treatment in older subjects with type 2 diabetes mellitus: A randomized trial. Hosp. Pract. (1995) 2013, 41, 72–84.
35. Yale, J.F.; Bakris, G.; Cariou, B.; Yue, D.; David-Neto, E.; Xi, L.; Figueroa, K.; Wajs, E.; Usiskin, K.; Meininger, G. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes. Metab. 2013, 15, 463–473.
36. Wilding, J.P.; Blonde, L.; Leiter, L.A.; Cerdas, S.; Tong, C.; Yee, J.; Meininger, G. Efficacy and safety of canagliflozin by baseline HbA1c and known duration of type 2 diabetes mellitus. J. Diabetes Complicat. 2015, 29, 438–444.
37. Yasui, A.; Lee, G.; Hirase, T.; Kaneko, T.; Kaspers, S.; von Eynatten, M.; Okamura, T. Empagliflozin Induces Transient Diuresis Without Changing Long-Term Overall Fluid Balance in Japanese Patients with Type 2 Diabetes. Diabetes Ther. 2018, 9, 863–871.
38. List, J.F.; Woo, V.; Morales, E.; Tang, W.; Fiedorek, F.T. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009, 32, 650–657.
39. Han, S.; Hagan, D.L.; Taylor, J.R.; Xin, L.; Meng, W.; Biller, S.A.; Wetterau, J.R.; Washburn, W.N.; Whaley, J.M. Dapagliflozin, a selective SGLT2 inhibitor, improves glucose homeostasis in normal and diabetic rats. Diabetes 2008, 57, 1723–1729.
40. Zhang, W.; Welihinda, A.; Mechanic, J.; Ding, H.; Zhu, L.; Lu, Y.; Deng, Z.; Sheng, Z.; Lv, B.; Chen, Y.; et al. EGT1442, a potent and selective SGLT2 inhibitor, attenuates blood glucose and HbA(1c) levels in db/db mice and prolongs the survival of stroke-prone rats. Pharmacol. Res. 2011, 63, 284–293.
41. Yamamoto, K.; Uchida, S.; Kitano, K.; Fukuhara, N.; Okumura-Kitajima, L.; Gunji, E.; Kozakai, A.; Tomoike, H.; Kojima, N.; Asami, J.; et al. TS-071 is a novel, potent and selective renal sodium-glucose cotransporter 2 (SGLT2) inhibitor with anti-hyperglycaemic activity. Br. J. Pharmacol. 2011, 164, 181–191.
42. Nagata, T.; Fukuzawa, T.; Takeda, M.; Fukazawa, M.; Mori, T.; Nihei, T.; Honda, K.; Suzuki, Y.; Kawabe, Y. Tofogliflozin, a novel sodium-glucose co-transporter 2 inhibitor, improves renal and pancreatic function in db/db mice. Br. J. Pharmacol. 2013, 170, 519–531.
43. Tahara, A.; Kurosaki, E.; Yokono, M.; Yamajuku, D.; Kihara, R.; Hayashizaki, Y.; Takasu, T.; Imamura, M.; Li, Q.; Tomiyama, H.; et al. Effects of SGLT2 selective inhibitor ipragliflozin on hyperglycemia, hyperlipidemia, hepatic steatosis, oxidative stress, inflammation, and obesity in type 2 diabetic mice. Eur. J. Pharmacol. 2013, 715, 246–255.
44. Lin, B.; Koibuchi, N.; Hasegawa, Y.; Sueta, D.; Toyama, K.; Uekawa, K.; Ma, M.; Nakagawa, T.; Kusaka, H.; Kim-Mitsuyama, S. Glycemic control with empagliflozin, a novel selective SGLT2 inhibitor, ameliorates cardiovascular injury and cognitive dysfunction in obese and type 2 diabetic mice. Cardiovasc. Diabetol. 2014, 13, 148.
45. 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. Ren. Physiol. 2015, 309, F227–F234.
46. Gallo, L.A.; Ward, M.S.; Fotheringham, A.K.; Zhuang, A.; Borg, D.J.; Flemming, N.B.; Harvie, B.M.; Kinneally, T.L.; Yeh, S.M.; McCarthy, D.A.; 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. 2016, 6, 26428.
47. 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. 2016, 3, 43.
48. Xu, L.; Nagata, N.; Nagashimada, M.; Zhuge, F.; Ni, Y.; Chen, G.; Mayoux, E.; Kaneko, S.; Ota, T. SGLT2 Inhibition by Empagliflozin Promotes Fat Utilization and Browning and Attenuates Inflammation and Insulin Resistance by Polarizing M2 Macrophages in Diet-induced Obese Mice. EBioMedicine 2017, 20, 137–149.
49. Wilding, J.P.; Norwood, P.; T’Joen, C.; Bastien, A.; List, J.F.; Fiedorek, F.T. A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers: Applicability of a novel insulin-independent treatment. Diabetes Care 2009, 32, 1656–1662.
50. Cherney, D.Z.; Perkins, B.A.; Soleymanlou, N.; Maione, M.; Lai, V.; Lee, A.; Fagan, N.M.; Woerle, H.J.; Johansen, O.E.; Broedl, U.C.; et al. Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus. Circulation 2014, 129, 587–597.
51. Sha, S.; Devineni, D.; Ghosh, A.; Polidori, D.; Hompesch, M.; Arnolds, S.; Morrow, L.; Spitzer, H.; Demarest, K.; Rothenberg, P. Pharmacodynamic effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, from a randomized study in patients with type 2 diabetes. PLoS ONE 2014, 9, e110069.
52. Sasaki, T.; Seino, Y.; Fukatsu, A.; Ubukata, M.; Sakai, S.; Samukawa, Y. Pharmacokinetics, Pharmacodynamics, and Safety of Luseogliflozin in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized, Single-blind, Placebo-controlled Trial. Adv. Ther. 2015, 32, 319–340.
53. Takeuchi, T.; Dohi, K.; Omori, T.; Moriwaki, K.; Sato, Y.; Nakamori, S.; Fujimoto, N.; Fujii, E.; Yamada, N.; Ito, M. Diuretic effects of sodium-glucose cotransporter 2 inhibitor in patients with type 2 diabetes mellitus and heart failure. Int. J. Cardiol. 2015, 201, 1–3.
54. Kawasoe, S.; Maruguchi, Y.; Kajiya, S.; Uenomachi, H.; Miyata, M.; Kawasoe, M.; Kubozono, T.; Ohishi, M. Mechanism of the blood pressure-lowering effect of sodium-glucose cotransporter 2 inhibitors in obese patients with type 2 diabetes. BMC Pharmacol. Toxicol. 2017, 18, 23.
55. Klein, J.D.; Rash, A.; Sands, J.M.; Ecelbarger, C.M.; Tiwari, S. Candesartan Differentially Regulates Epithelial Sodium Channel in Cortex Versus Medulla of Streptozotocin-Induced Diabetic Rats. J. Epithel. Biol. Pharmacol. 2009, 2, 23.
56. Song, J.; Knepper, M.A.; Verbalis, J.G.; Ecelbarger, C.A. Increased renal ENaC subunit and sodium transporter abundances in streptozotocin-induced type 1 diabetes. Am. J. Physiol. Ren. Physiol. 2003, 285, F1125–F1137.
57. Kim, D.; Sands, J.M.; Klein, J.D. Changes in renal medullary transport proteins during uncontrolled diabetes mellitus in rats. Am. J. Physiol. Ren. Physiol. 2003, 285, F303–F309.
58. Harris, R.C.; Brenner, B.M.; Seifter, J.L. Sodium-hydrogen exchange and glucose transport in renal microvillus membrane vesicles from rats with diabetes mellitus. J. Clin. Investig. 1986, 77, 724–733.
59. Madala Halagappa, V.K.; Tiwari, S.; Riazi, S.; Hu, X.; Ecelbarger, C.M. Chronic candesartan alters expression and activity of NKCC2, NCC, and ENaC in the obese Zucker rat. Am. J. Physiol. Ren. Physiol. 2008, 294, F1222–F1231.
60. Chavez-Canales, M.; Arroyo, J.P.; Ko, B.; Vazquez, N.; Bautista, R.; Castaneda-Bueno, M.; Bobadilla, N.A.; Hoover, R.S.; Gamba, G. Insulin increases the functional activity of the renal NaCl cotransporter. J. Hypertens. 2013, 31, 303–311.
61. Layton, A.T.; Vallon, V.; Edwards, A. Predicted consequences of diabetes and SGLT inhibition on transport and oxygen consumption along a rat nephron. Am. J. Physiol. Ren. Physiol. 2016, 310, F1269–F1283.
62. 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. 2014, 25, 2028–2039.
63. Fu, Y.; Gerasimova, M.; Mayoux, E.; Masuda, T.; Vallon, V. Acute and Chronic Cmplications. Diabetes 2014, 63, A103–A170.
64. Novikov, A.; Vallon, V. Sodium glucose cotransporter 2 inhibition in the diabetic kidney: An update. Curr. Opin. Nephrol. Hypertens. 2016, 25, 50–58.
65. Cassis, P.; Locatelli, M.; Cerullo, D.; Corna, D.; Buelli, S.; Zanchi, C.; Villa, S.; Morigi, M.; Remuzzi, G.; Benigni, A.; et al. SGLT2 inhibitor dapagliflozin limits podocyte damage in proteinuric nondiabetic nephropathy. JCI Insight 2018, 3.
66. Takiyama, Y.; Sera, T.; Nakamura, M.; Ishizeki, K.; Saijo, Y.; Yanagimachi, T.; Maeda, M.; Bessho, R.; Takiyama, T.; Kitsunai, H.; et al. Impacts of Diabetes and an SGLT2 Inhibitor on the Glomerular Number and Volume in db/db Mice, as Estimated by Synchrotron Radiation Micro-CT at SPring-8. EBioMedicine 2018, 36, 329–346.
67. Vallon, V.; Gerasimova, M.; Rose, M.A.; Masuda, T.; Satriano, J.; Mayoux, E.; Koepsell, H.; Thomson, S.C.; Rieg, T. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. Am. J. Physiol. Ren. Physiol. 2014, 306, F194–F204.
68. Nishiyama, A.; Kobori, H. Independent regulation of renin-angiotensin-aldosterone system in the kidney. Clin. Exp. Nephrol. 2018, 22, 1231–1239.
69. Li, L.; Konishi, Y.; Morikawa, T.; Zhang, Y.; Kitabayashi, C.; Kobara, H.; Masaki, T.; Nakano, D.; Hitomi, H.; Kobori, H.; et al. Effect of a SGLT2 inhibitor on the systemic and intrarenal renin-angiotensin system in subtotally nephrectomized rats. J. Pharmacol. Sci. 2018, 137, 220–223.
70. Kobori, H.; Navar, L.G. Urinary Angiotensinogen as a Novel Biomarker of Intrarenal Renin-Angiotensin System in Chronic Kidney Disease. Int. Rev. Thromb. 2011, 6, 108–116.
71. Nijst, P.; Verbrugge, F.H.; Martens, P.; Bertrand, P.B.; Dupont, M.; Francis, G.S.; Tang, W.W.; Mullens, W. Plasma renin activity in patients with heart failure and reduced ejection fraction on optimal medical therapy. J. Renin Angiotensin Aldosterone Syst. 2017, 18, 1470320317729919.
72. Kobori, H.; Harrison-Bernard, L.M.; Navar, L.G. Urinary excretion of angiotensinogen reflects intrarenal angiotensinogen production. Kidney Int. 2002, 61, 579–585.
73. Satirapoj, B.; Siritaweesuk, N.; Supasyndh, O. Urinary angiotensinogen as a potential biomarker of diabetic nephropathy. Clin. Kidney J. 2014, 7, 354–360.
74. Shin, S.J.; Chung, S.; Kim, S.J.; Lee, E.M.; Yoo, Y.H.; Kim, J.W.; Ahn, Y.B.; Kim, E.S.; Moon, S.D.; Kim, M.J.; et al. Effect of Sodium-Glucose Co-Transporter 2 Inhibitor, Dapagliflozin, on Renal Renin-Angiotensin System in an Animal Model of Type 2 Diabetes. PLoS ONE 2016, 11, e0165703.
75. Yoshimoto, T.; Furuki, T.; Kobori, H.; Miyakawa, M.; Imachi, H.; Murao, K.; Nishiyama, A. Effects of sodium-glucose cotransporter 2 inhibitors on urinary excretion of intact and total angiotensinogen in patients with type 2 diabetes. J. Investig. Med. 2017, 65, 1057–1061.
76. MORI, I.; ISHIZUKA, T. Effects of SGLT2 Inhibitors on Renin-Aldosterone System for One Month and Six Months in Type 2 Diabetes. Diabetes 2018, 67.
77. Nomiyama, T.; Shimono, D.; Horikawa, T.; Fujimura, Y.; Ohsako, T.; Terawaki, Y.; Fukuda, T.; Motonaga, R.; Tanabe, M.; Yanase, T.; et al. Efficacy and safety of sodium-glucose cotransporter 2 inhibitor ipragliflozin on glycemic control and cardiovascular parameters in Japanese patients with type 2 diabetes mellitus; Fukuoka Study of Ipragliflozin (FUSION). Endocr. J. 2018, 65, 859–867.
78. Lijnen, P.; Fagard, R.; Staessen, J.; Amery, A. Effect of chronic diuretic treatment on the plasma renin-angiotensin-aldosterone system in essential hypertension. Br. J. Clin. Pharmacol. 1981, 12, 387–392.
79. Vaughan, E.D., Jr.; Carey, R.M.; Peach, M.J.; Ackerly, J.A.; Ayers, C.R. The renin response to diuretic therapyl A limitation of antihypertensive potential. Circ. Res. 1978, 42, 376–381.
80. Komoroski, B.; Vachharajani, N.; Feng, Y.; Li, L.; Kornhauser, D.; Pfister, M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin. Pharmacol. Ther. 2009, 85, 513–519.
81. Hollenberg, N.K.; Stevanovic, R.; Agarwal, A.; Lansang, M.C.; Price, D.A.; Laffel, L.M.; Williams, G.H.; Fisher, N.D. Plasma aldosterone concentration in the patient with diabetes mellitus. Kidney Int. 2004, 65, 1435–1439.
82. Budoff, M.J.; Wilding, J.P.H. Effects of canagliflozin on cardiovascular risk factors in patients with type 2 diabetes mellitus. Int. J. Clin. Pract. 2017, 71.
83. Pfeifer, M.; Townsend, R.R.; Davies, M.J.; Vijapurkar, U.; Ren, J. Effects of canagliflozin, a sodium glucose co-transporter 2 inhibitor, on blood pressure and markers of arterial stiffness in patients with type 2 diabetes mellitus: A post hoc analysis. Cardiovasc. Diabetol. 2017, 16, 29.
84. Rahman, A.; Fujisawa, Y.; Nakano, D.; Hitomi, H.; Nishiyama, A. Effect of a selective SGLT2 inhibitor, luseogliflozin, on circadian rhythm of sympathetic nervous function and locomotor activities in metabolic syndrome rats. Clin. Exp. Pharmacol. Physiol. 2017, 44, 522–525.
85. Wan, N.; Rahman, A.; Hitomi, H.; Nishiyama, A. The Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Sympathetic Nervous Activity. Front. Endocrinol. (Lausanne) 2018, 9, 421.
86. Matsusaka, T.; Niimura, F.; Shimizu, A.; Pastan, I.; Saito, A.; Kobori, H.; Nishiyama, A.; Ichikawa, I. Liver angiotensinogen is the primary source of renal angiotensin II. J. Am. Soc. Nephrol. 2012, 23, 1181–1189.
87. Kobori, H.; Nishiyama, A.; Harrison-Bernard, L.M.; Navar, L.G. Urinary angiotensinogen as an indicator of intrarenal Angiotensin status in hypertension. Hypertension 2003, 41, 42–49.
88. Wang, J.; Shibayama, Y.; Kobori, H.; Liu, Y.; Kobara, H.; Masaki, T.; Wang, Z.; Nishiyama, A. High glucose augments angiotensinogen in human renal proximal tubular cells through hepatocyte nuclear factor-5. PLoS ONE 2017, 12, e0185600.
89. Fan, Y.Y.; Kobori, H.; Nakano, D.; Hitomi, H.; Mori, H.; Masaki, T.; Sun, Y.X.; Zhi, N.; Zhang, L.; Huang, W.; et al. Aberrant activation of the intrarenal renin-angiotensin system in the developing kidneys of type 2 diabetic rats. Horm. Metab. Res. 2013, 45, 338–343.
90. Saito, T.; Urushihara, M.; Kotani, Y.; Kagami, S.; Kobori, H. Increased urinary angiotensinogen is precedent to increased urinary albumin in patients with type 1 diabetes. Am. J. Med. Sci. 2009, 338, 478–480.
91. Lee, M.J.; Kim, S.S.; Kim, I.J.; Song, S.H.; Kim, E.H.; Seo, J.Y.; Kim, J.H.; Kim, S.; Jeon, Y.K.; Kim, B.H.; et al. Changes in Urinary Angiotensinogen Associated with Deterioration of Kidney Function in Patients with Type 2 Diabetes Mellitus. J. Korean Med. Sci. 2017, 32, 782–788.
92. Lei, L.; Nishiyama, A. A4490 Effects of esaxerenone (CS-3150), a non-steroidal selective of mineralocorticoid receptor antagonist, on blood pressure and renal injury in Dahl salt-sensitive rats. J. Hypertens. 2018, 36, e18.