PMID- 30937117 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220408 IS - 1918-3003 (Print) IS - 1918-3011 (Electronic) IS - 1918-3003 (Linking) VI - 11 IP - 4 DP - 2019 Apr TI - Renoprotective Effects of Additional SGLT2 inhibitor Therapy in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease Stages 3b-4: A Real World Report From A Japanese Specialized Diabetes Care Center. PG - 267-274 LID - 10.14740/jocmr3761 [doi] AB - BACKGROUND: Large randomized clinical trials of patients with type 2 diabetes mellitus (T2DM) and at high risk for cardiovascular disease revealed that sodium-glucose cotransporter 2 (SGLT2) inhibitors significantly reduced renal events. However, the trials included small numbers of patients with moderate-to-severe chronic kidney disease (CKD). Therefore, the renoprotective effects of SGLT2 inhibitors remain unknown in T2DM patients complicated with impaired renal function. We examined if SGLT2 inhibitors conferred beneficial effects on kidney function in T2DM patients with CKD. METHODS: We retrospectively recruited T2DM patients who were newly treated with add-on of SGLT2 inhibitors and suffered from moderate-to-severe renal impairment with CKD stages 3b-4 (15 < estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m(2)), at initiation of SGLT2 inhibitor therapy. We analyzed T2DM patients with moderate-to-severe renal impairment who continued to use SGLT2 inhibitors for at least 1 year. We investigated the effects of SGLT2 inhibitor therapy on 1-year changes in eGFR and urinary protein excretion before and after the treatment. RESULTS: We analyzed 42 T2DM patients with median eGFR of 40.4 mL/min/1.73 m(2). One-year SGLT2 inhibitor therapy lowered median hemoglobin A1c (HbA1c) levels from 7.6% to 7.5% (not significant). Body weight and blood pressure were significantly decreased, and hemoglobin was significantly increased. The median value of eGFR after 1 year of SGLT2 inhibitor therapy was 41.0 mL/min/1.73 m(2), with no significant difference compared with baseline. The annual decline in eGFR improved significantly after SGLT2 inhibitor therapy (eGFR: (median), pre: -3.8, vs. post: 0.1 mL/min/1.73 m(2) per year, P < 0.01). We also found a significant decrease in urinary protein excretion after SGLT2 inhibitor therapy (urinary protein-to-creatinine ratio: (median), pre: 0.36, vs. post: 0.23 g/g creatinine, n = 35, P < 0.01). CONCLUSIONS: This study revealed the promising observations that add-on treatment with SGLT2 inhibitors exerted significant renoprotective effects, culminating in improvements in annual decline in eGFR and urinary protein excretion in T2DM patients with CKD stages 3b-4, but did not significantly reduce HbA1c. Further prospective clinical trials are warranted to fully elucidate the effects of SGLT2 inhibitors on glycemic control and renal function in T2DM patients with moderate-to-severe renal impairment. FAU - Sugiyama, Seigo AU - Sugiyama S AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Cardiovascular Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - They contributed equally to this study. FAU - Jinnouchi, Hideaki AU - Jinnouchi H AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Cardiovascular Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Division of Preventive Cardiology, Department of Cardiovascular Medicine, Kumamoto University Hospital, Kumamoto, Japan. AD - They contributed equally to this study. FAU - Yoshida, Akira AU - Yoshida A AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Pharmacology Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Hieshima, Kunio AU - Hieshima K AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Infectious Disease Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Kurinami, Noboru AU - Kurinami N AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Obesity Treatment Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Jinnouchi, Katsunori AU - Jinnouchi K AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Gastroenterology Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Hemodialysis Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Tanaka, Motoko AU - Tanaka M AD - Department of Nephrology, Akebono Clinic, Kumamoto, Japan. FAU - Suzuki, Tomoko AU - Suzuki T AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Cardiovascular Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Miyamoto, Fumio AU - Miyamoto F AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Ophthalmology Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Kajiwara, Keizo AU - Kajiwara K AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Cardiovascular Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Obesity Treatment Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. FAU - Jinnouchi, Tomio AU - Jinnouchi T AD - Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Cardiovascular Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. AD - Obesity Treatment Division, Diabetes Care Center, Jinnouchi Hospital, Kumamoto, Japan. LA - eng PT - Journal Article DEP - 20190318 PL - Canada TA - J Clin Med Res JT - Journal of clinical medicine research JID - 101538301 PMC - PMC6436561 OTO - NOTNLM OT - Annual eGFR decline OT - Estimated glomerular filtration rate OT - Kidney OT - Rapid eGFR decliner OT - Renoprotection OT - Sodium-glucose co-transporter 2 inhibitors OT - Type 2 diabetes mellitus OT - Urine protein-to-creatinine ratio COIS- Dr. Seigo Sugiyama is on the Speaker's Bureau of MSD, Inc., and AstraZeneca Pharmaceuticals LP, Ono Pharmaceutical CO., LTD, and Bayer Yakuhin Ltd. Dr. Hideaki Jinnouchi has received consultant fees from Sanofi U.S., Novo Nordisk, Inc., and Eli Lilly Japan K.K. Dr. Hideaki Jinnouchi is also on the Speaker's Bureau of MSD, Inc., Astellas Pharma US, Inc., Sanofi U.S., Novo Nordisk Pharma, Ltd., Taisho Toyama Pharmaceutical, Co., Ltd. Daiichi-Sankyo Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Eli Lilly Japan K.K., Boehringer Ingelheim Pharmaceuticals, Inc., Takeda Pharmaceutical Company Limited, and AstraZeneca Pharmaceuticals LP. All other authors declare that they have no conflicts of interest. EDAT- 2019/04/03 06:00 MHDA- 2019/04/03 06:01 PMCR- 2019/03/18 CRDT- 2019/04/03 06:00 PHST- 2019/01/21 00:00 [received] PHST- 2019/02/22 00:00 [accepted] PHST- 2019/04/03 06:00 [entrez] PHST- 2019/04/03 06:00 [pubmed] PHST- 2019/04/03 06:01 [medline] PHST- 2019/03/18 00:00 [pmc-release] AID - 10.14740/jocmr3761 [doi] PST - ppublish SO - J Clin Med Res. 2019 Apr;11(4):267-274. doi: 10.14740/jocmr3761. Epub 2019 Mar 18.