Satirapoj Bancha, Korkiatpitak Pattharamon, Supasyndh Ouppatham
Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand.
Clin Kidney J. 2019 Jan 4;12(3):326-332. doi: 10.1093/ckj/sfy122. eCollection 2019 Jun.
Intensive glucose control reduces the risk for microvascular complications in type 2 diabetes (T2DM). Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to exert renoprotection beyond glycemic control, although their effects on the organs are not well known. There are limited data on SGLT2 inhibitors for the biomarkers of kidney injury in type 2 diabetes mellitus (T2DM) patients.
Our objective was to demonstrate the effect of SGLT2 inhibitors on proximal tubular injury and function in patients with T2DM.
T2DM patients with persistent glycated hemoglobin (HbA1c) levels >7% were randomly assigned to either dapagliflozin 10 mg/day ( = 28) or standard treatment ( = 29) for 12 weeks. Proximal tubular injury biomarkers, including urine kidney injury molecule-1:creatinine ratio (UKIM1CR), urine cystatin C:creatinine ratio (UCCR), urine albumin:creatinine ratio (UACR), fractional excretion of phosphate (FEPO) and fractional excretion of uric acid (FEUA) were measured at baseline and study end.
Baseline characteristics were comparable between treatment groups. After 12 weeks, dapagliflozin-treated versus standard-treated patients showed reductions in HbA1c (-0.75 ± 0.21 versus -0.70 ± 0.25%; P = 0.882). There were significant between-group differences in the reduction in UACR {-23.3 [95% confidence interval (CI) -44.4 to -2.2] versus +19.9 (-4.0-43.8) mg/g Cr; P = 0.010} and UKIM1CR [-26.7 (95% CI -232.9-179.5) versus +422.2 (46.7-797.7) ng/g Cr; P = 0.047], but no significant difference in changes in UCCR between the two groups. There was no significant change in glomerular filtration rate, serum phosphate level, FEUA and FEPO in the dapagliflozin group. No serious renal-related adverse events were observed in either group.
This study indicates that dapagliflozin in T2DM patients can decrease the levels of urinary proximal tubular injury biomarkers, thus highlighting its renoprotective effect. SGLT2 inhibitors could prove useful in treating T2DM by protecting against renal tubular injury and may lead to reduced long-term renal outcomes.
强化血糖控制可降低2型糖尿病（T2DM）微血管并发症的风险。最近，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂已被证明除血糖控制外还具有肾脏保护作用，尽管其对各器官的影响尚不清楚。关于SGLT2抑制剂对2型糖尿病（T2DM）患者肾脏损伤生物标志物影响的数据有限。
我们的目的是证明SGLT2抑制剂对T2DM患者近端肾小管损伤和功能的影响。
糖化血红蛋白（HbA1c）持续水平>7%的T2DM患者被随机分配至达格列净10mg/天组（n=28）或标准治疗组（n=29），为期12周。在基线和研究结束时测量近端肾小管损伤生物标志物，包括尿肾损伤分子-1与肌酐比值（UKIM1CR）、尿胱抑素C与肌酐比值（UCCR）、尿白蛋白与肌酐比值（UACR）、磷酸盐排泄分数（FEPO）和尿酸排泄分数（FEUA）。
治疗组间基线特征具有可比性。12周后，达格列净治疗组与标准治疗组患者的HbA1c均有所降低（-0.75±0.21对-0.70±0.25%；P=0.882）。UACR降低幅度组间差异有统计学意义{-23.3[95%置信区间（CI）-44.4至-2.2]对+19.9（-4.0至43.8）mg/g Cr；P=0.010}，UKIM1CR降低幅度组间差异有统计学意义[-26.7（95%CI-232.9至179.5）对+422.2（46.7至797.7）ng/g Cr；P=0.047]，但两组间UCCR变化无显著差异。达格列净组肾小球滤过率、血清磷酸盐水平、FEUA和FEPO无显著变化。两组均未观察到严重的肾脏相关不良事件。
本研究表明，达格列净可降低T2DM患者尿近端肾小管损伤生物标志物水平，从而突出其肾脏保护作用。SGLT2抑制剂可能通过预防肾小管损伤对治疗T2DM有用，并可能导致长期肾脏结局改善。
