Effect of canagliflozin on urinary albumin / creatinine ratio and urinary podocyte-associated protein nephrin in patients with early diabetic kidney disease

Abstract

Abstract:

ObjectiveTo investigate the effect of canagliflozin (sodium-glucose cotransporter 2 inhibitor, SGLT-2i) on the ratio of urine albumin-to-creatinine ratio(UACR) and urine podocyte-related protein nephrin in early diabetic nephropathy.MethodsFrom January 2018 to July 2019, 116 patients with early diabetic nephropathy who were hospitalized in the Department of Endocrinology, Southern University of Science and Technology Hospital were enrolled. They were divided into canagliflozin group and control group with 1∶1 random number method. One hundred and five(90.5%) patients completed all studies, 51 were in the canagliflozin group and 54 were in the control group. The canagliflozin group was routinely given canagliflozin 100-300 mg/d, the control group received basal insulin and losartan potassium tablets 100 mg/d, and the patients in both groups were treated 24 weeks. The biochemical indicators of the patients were tested before treatment, 12-weeks and 24-weeks treatment. The UACR and the urine podocyte-associated protein nephrin before and after treatment were compared between groups and within groups.ResultsCompared with before treatment, both UACR and nephrin in the canagliflozin and the control groups improved after 12 weeks and 24 weeks treatment (P<0.05). Before treatment and after 12-weeks treatment, the UACR and nephrin indexes in canagliflozin and control groups didn’t show significant difference (P>0.05); while after 24-weeks treatment, these indexes in the canagliflozin group were significantly better than the control group(P<0.05).ConclusionsCanagliflozin can continuously reduce the content of podocyte-associated protein nephrin in urine of early diabetic nephropathy. It is speculated that the renal protection of SGLT-2i drugs is independent of the effect of lowering the blood sugar.

Key words:Canagliflozin,Sodium-glucose cotransporter 2 inhibitor,Diabetic kidney disease,Urinary albumin-to-creatinine ratio,Podocyte associated protein

CLC Number:

R587.1

SUN Yan, DAI Danjiao, CHEN Zhiwei, ZHANG Huaqing. Effect of canagliflozin on urinary albumin / creatinine ratio and urinary podocyte-associated protein nephrin in patients with early diabetic kidney disease[J]. Journal of Internal Medicine Concepts & Practice, 2021, 16(06): 387-391.

Figures/Tables3

项目	对照组（n=54）	卡格列净组（n=51）	t/χ²	P
年龄（岁）	44.61±7.89	46.54±6.18	0.653	0.69
男性 [n（%）]	30（55.5）	29（56.8）	0.385	0.87
病程（月）	13.24±2.67	12.52±2.54	0.410	0.81
其他药物使用 [n（%）]
调脂药	26（48.2）	25（49.1）	0.721	0.61
降压药	20（37.0）	18（35.2）	0.952	0.58
BMI（kg/m²）	24.44±3.06	23.58±3.77	0.994	0.55
WHR（m）	0.91±0.06	0.89±0.08	0.520	0.76
SBP（mmHg）	137.08±20.66	135.89±18.94	0.531	0.78
DBP（mmHg）	77.23±9.14	75.34±8.91	0.895	0.56
FPG（mmol/L）	9.02±0.89	8.94±0.77	0.356	0.84
PPG（mmol/L）	13.81±3.31	12.71±2.98	0.221	0.92
HbA_1c（%）	7.72±1.78	7.30±1.82	0.512	0.79
TG(mmol/L）	3.08±0.29	2.87±0.31	1.058	0.40
TC（mmol/L）	5.98±1.85	6.00±1.79	0.021	0.96
LDL-C（mmol/L）	3.14±0.17	3.05±0.16	0.934	0.58
UA（mmol/L）	311.09±31.82	305.16±38.43	1.128	0.34

项目	对照组（n=54）	卡格列净组（n=51）	t	P
FPG（mmol/L）
治疗12周	7.11±0.95	6.62±0.67	-0.129	0.178
治疗24周	6.58±0.43	6.43±0.56	-1.090	0.059
PPG（mmHg）
治疗12周	8.77±1.99	8.98±2.12	0.086	0.897
治疗24周	8.18±1.87	8.07±1.98	-1.828	0.071
HbA_1c（%）
治疗12周	6.12±0.67	6.17±0.78	1.281	0.302
治疗24周	5.97±0.73	6.02±0.64	-0.118	0.928
LDL-C（mmol/L）
治疗12周	2.69±0.95	2.76±0.91	-0.172	0.864
治疗24周	2.22±0.43	2.31±0.66	-1.080	0.057
SBP（mmHg）
治疗12周	127.5±44.0	130.4±42.8	0.289	0.776
治疗24周	123.2±30.6	127.1±28.7	-1.273	0.054
UA（mmol/L）
治疗12周	300.3±88.7	296.6±85.1	-1.828	0.071
治疗24周	278.3±73.5	224.5±64.4	-2.107	0.038
WHR（m）
治疗12周	0.87±0.07	0.85±0.06	0.009	0.496
治疗24周	0.86±0.08	0.82±0.05	5.181	0.000
BMI(kg/m²)
治疗12周	23.44±3.10	22.45±3.12	0.016	0.494
治疗24周	22.89±3.02	21.01±3.05	4.057	0.000

项目	对照组（n=54）	卡格列净组（n=51）	t	P
治疗前
UACR(mg/g)	45.9±9.5	46.8±8.2	0.069	0.793
裂隙素(μg/L)	5.85±1.3	6.12±1.2	1.026	0.41
治疗12周
UACR(mg/g)	42.7±9.2^1）	41.5±9.1^1）	0.521	0.687
裂隙素(μg/L)	5.1±0.79^1）	5.0±0.98^1）	0.687	0.572
治疗24周
UACR(mg/g)	39.5±4.33^1）	34±4.58^1）2）3）	4.029	<0.05
裂隙素(μg/L)	4.55±0.23^1）	3.05±0.17^{1）2）3）4）}	6.328	<0.001

References19

[1]	Audzeyenka I, Rogacka D, Piwkowska A, et al. Viability of primary cultured podocytes is associated with extracellular high glucose-dependent autophagy downregulation[J]. Mol Cell Biochem, 2017, 430(1-2): 11-19. doi:10.1007/s11010-017-2949-5pmid:28236091
[2]	中华医学会内分泌学分会. 中国成人糖尿病肾脏病临床诊断的专家共识[J]. 中国内分泌代谢杂志, 2015, 31(5): 379-385.
[3]	Kumar Pasupulati A, Chitra PS, Reddy GB. Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy[J]. Biomol Concepts, 2016, 7(5-6): 293-309. doi:10.1515/bmc-2016-0021pmid:27816946
[4]	Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy[J]. N Engl J Med, 2019, 380(24): 2295-2306. doi:10.1056/NEJMoa1811744 URL
[5]	Li W, Du M, Wang Q, et al. FoxO1 promotes mitophagy in the podocytes of diabetic male mice via the PINK1/Parkin pathway[J]. Endocrinology, 2017, 158(7): 2155-2167. doi:10.1210/en.2016-1970 URL
[6]	Lioudaki E, Stylianou KG, Petrakis I, et al. Increased urinary excretion of podocyte markers in normoalbuminuric patients with diabetes[J]. Nephron, 2015, 131(1): 34-42. doi:10.1159/000438493 URL
[7]	中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2017年版)[J]. 中华糖尿病杂志, 2018, 10(4): 4-67.
[8]	Koye DN, Magliano DJ, Reid CM, et al. Risk of progression of nonalbuminuric CKD to end-stage kidney disease in people with diabetes[J]. Am J Kidney Dis, 2018, 72(5): 653-661. doi:10.1053/j.ajkd.2018.02.364 URL
[9]	Cho NH, Shaw JE, Karuranga S, et al. IDF diabetes atlas: global estimates of diabetes prevalence for 2017 and projections for 2045[J]. Diabetes Res Clin Pract, 2018, 138: 271-281. doi:10.1016/j.diabres.2018.02.023 URL
[10]	Ito Y, Hsu MF, Bettaieb A, et al. Protein tyrosine phosphatase 1B deficiency in podocytes mitigates hyperglycemia-induced renal injury[J]. Metabolism, 2017, 76: 56-69. doi:10.1016/j.metabol.2017.07.009 URL
[11]	Jiang XS, Chen XM, Wan JM, et al. Autophagy protects against palmitic acid-induced apoptosis in podocytes in vitro[J]. Sci Rep, 2017, 7: 42-64. doi:10.1038/s41598-017-00093-z URL
[12]	Garofalo C, Borrelli S, Liberti ME, et al. SGLT2 inhibitors: nephroprotective efficacy and side effects[J]. Medicina (Kaunas), 2019, 55(6): E268.
[13]	Lee YL, Chen BK, Lin KD, et al. The impact of severe hypoglycemia on renal impairment in type 2 diabetes[J]. Diabetes Res Clin Pract, 2015, 108(3): 448-455. doi:10.1016/j.diabres.2015.02.028 URL
[14]	Sakai S, Kaku K, Seino Y, et al. Efficacy and safety of the SGLT2 inhibitor luseogliflozin in Japanese patients with type 2 diabetes mellitus stratified according to baseline body mass index[J]. Clin Ther, 2016, 38(4): 843-862. doi:10.1016/j.clinthera.2016.01.017 URL
[15]	李宁, 高政南, 李欣宇, 等. 卡格列净联合胰岛素治疗肥胖或超重2型糖尿病患者的临床观察[J]. 中国慢性病预防与控制, 2019, 191(9): 66-68.
[16]	Inagaki N, Harashima S, Maruyama N, et al. Efficacy and safety of canagliflozin in combination with insulin: a double-blind, randomized, placebo-controlled study in Japanese patients with type 2 diabetes mellitus[J]. Cardiovasc Diabetol, 2016, 15: 89. doi:10.1186/s12933-016-0407-4pmid:27316668
[17]	Yale JF, Bakris G, Cariou B, et al. Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease[J]. Diabetes Obes Metab, 2013, 15(5): 463-473. doi:10.1111/dom.12090pmid:23464594
[18]	Zuo H, Wang S, Feng J, et al. BRD4 contributes to high-glucose-induced podocyte injury by modulating Keap1/Nrf2/ARE signaling[J]. Biochimie, 2019, 165: 100-107. doi:10.1016/j.biochi.2019.07.012 URL
[19]	王荣珍, 姚灿, 刘沨. nephrin表达与糖尿病肾病预后相关性研究[J]. 临床荟萃, 2019, 34(5): 431-435.