Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers.
Effects of the SGLT-2 inhibitor dapagliflozin on glomerular and tubular injury markers.
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DOI：
10.1111/dom.13301
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发表时间：
2018-08
期刊：
影响因子：
--
通讯作者：
Heerspink HJL
中科院分区：
文献类型：
--
作者：
Dekkers CCJ;Petrykiv S;Laverman GD;Cherney DZ;Gansevoort RT;Heerspink HJL
SGLT‐2抑制剂降低蛋白尿的机制尚不完全清楚。我们在一项交叉试验的事后分析中评估了SGLT2抑制剂达格列净对肾小球标志物（IgG - IgG4和IgG -白蛋白）、小管标志物（尿KIM‐1、NGAL和LFABP）和炎症标志物（尿MCP‐1和IL‐6）的影响，以提供更多关于肾脏保护作用的信息。与安慰剂相比，达格列净降低蛋白尿43.9% (95% CI, 30.3%‐54.8%)，eGFR降低5.1(2.0‐8.1)mL/min/1.73m2。与安慰剂相比，达格列净没有改变肾小球电荷或大小选择性指数。达格列净减少尿中KIM‐1排泄22.6%(0.3%‐39.8%;P =。05)和IL 6排泄23.5%(1.4%还是40.6%;P =。与安慰剂相比，NGAL、LFABP和MCP‐1没有变化。在达格列净治疗期间，蛋白尿的变化与eGFR的变化相关(r = 0.36; P =。0.05)和KIM‐1 （r = 0.39; P = 0.05）。综上所述，6周的达格列净治疗降低蛋白尿的效果可能是降低肾小球内压力或减轻小管细胞损伤的结果。
The mechanisms by which SGLT‐2 inhibitors lower albuminuria are incompletely understood. We assessed in a post‐hoc analysis of a cross‐over trial the effects of the SGLT2 inhibitor dapagliflozin on glomerular markers (IgG to IgG4 and IgG to albumin), tubular markers (urinary KIM‐1, NGAL and LFABP) and inflammatory markers (urinary MCP‐1 and IL‐6) to provide more insight into kidney protective effects. Dapagliflozin decreased albuminuria by 43.9% (95% CI, 30.3%‐54.8%) and eGFR by 5.1 (2.0‐8.1) mL/min/1.73m2 compared to placebo. Dapagliflozin did not change glomerular charge or size selectivity index compared to placebo. Dapagliflozin decreased urinary KIM‐1 excretion by 22.6% (0.3%‐39.8%; P = .05) and IL‐6 excretion by 23.5% (1.4%‐40.6%; P = .04) compared to placebo, whereas no changes in NGAL, LFABP and MCP‐1 were observed. During dapagliflozin treatment, changes in albuminuria correlated with changes in eGFR (r = 0.36; P = .05) and KIM‐1 (r = 0.39; P = .05). In conclusion, the albuminuria‐lowering effect of 6 weeks of dapagliflozin therapy may be the result of decreased intraglomerular pressure or reduced tubular cell injury.
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影响因子：
3.7
作者：
Panchapakesan U;Pegg K;Gross S;Komala MG;Mudaliar H;Forbes J;Pollock C;Mather A
通讯作者：
Mather A
影响因子：
13.6
作者：
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DOI：
10.1152/ajprenal.00331.2013
发表时间：
2014-04-01
影响因子：
4.2
作者：
Lin, Qiongzhen;Chen, Ying;Yang, Li
通讯作者：
Yang, Li
影响因子：
37.8
作者：
Heerspink, Hiddo J. L.;Perkins, Bruce A.;Cherney, David Z. I.
通讯作者：
Cherney, David Z. I.
影响因子：
5
作者：
Tahara, Atsuo;Kurosaki, Eiji;Shibasaki, Masayuki
通讯作者：
Shibasaki, Masayuki