Osanami Arata, Komatsu Hiroaki, Gocho Yufu, Nishizawa Keitaro, Tanaka Marenao, Nakamura Yuichi, Furuhashi Masato
Department of Cardiovascular, Renal, and Metabolic Medicine, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-Ku, Sapporo, 060-8556, Japan.
Department of Cardiology, Steel Memorial Muroran Hospital, Muroran, Japan.
Clin Exp Nephrol. 2025 Jan 20. doi: 10.1007/s10157-025-02625-8.
Several clinical trials showed that sodium-glucose cotransporter 2 (SGLT2) inhibitors have protective effects against chronic kidney disease (CKD) in both patients with and those without type 2 diabetes mellitus. Since one of the renoprotective mechanisms of SGLT2 inhibitors is thought to be amelioration of glomerular hyperfiltration, we hypothesized that an enlarged glomerular diameter, which suggests increased single-nephron glomerular filtration rate, is associated with a reduction in urinary protein after treatment with an SGLT2 inhibitor.
This study was a retrospective multicentered study including 28 adult patients with CKD who underwent kidney biopsy and were then treated with dapagliflozin, an SGLT2 inhibitor. The association of glomerular diameter with changes in urinary protein 4-8 weeks after the initiation of treatment with dapagliflozin was investigated.
Maximum glomerular diameter was significantly and positively correlated with change in urinary protein-to-creatinine ratio (UPCR) (R = 0.44; P < 0.001). Maximum glomerular diameter was significantly larger in patients who achieved ≥ 30% reduction in UPCR after the initiation of treatment with dapagliflozin than in patients who achieved < 30% reduction in UPCR (219.4 ± 23.9 vs. 188.0 ± 29.0; P = 0.005). After adjustment of age, sex and estimated glomerular filtration rate, maximum glomerular diameter was independently associated with change in UPCR (β = 0.645, P < 0.001). Furthermore, maximum glomerular diameter was independently associated with ≥ 30% reduction in UPCR (odds ratio: 1.07, 95% confidential interval: 1.01-1.14).
Glomerular diameter is independently associated with an early change in UPCR after the initiation of treatment with dapagliflozin in patients with CKD.
多项临床试验表明，钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂对2型糖尿病患者和非2型糖尿病患者的慢性肾脏病（CKD）均具有保护作用。由于SGLT2抑制剂的肾脏保护机制之一被认为是改善肾小球高滤过，我们推测肾小球直径增大（提示单肾单位肾小球滤过率增加）与SGLT2抑制剂治疗后尿蛋白减少有关。
本研究为一项回顾性多中心研究，纳入28例接受肾活检并随后接受SGLT2抑制剂达格列净治疗的成年CKD患者。研究了达格列净治疗开始后4-8周肾小球直径与尿蛋白变化的相关性。
最大肾小球直径与尿蛋白肌酐比值（UPCR）的变化显著正相关（R = 0.44；P < 0.001）。达格列净治疗开始后UPCR降低≥30%的患者的最大肾小球直径显著大于UPCR降低<30%的患者（219.4±23.9 vs. 188.0±29.0；P = 0.005）。在调整年龄、性别和估计肾小球滤过率后，最大肾小球直径与UPCR的变化独立相关（β = 0.645，P < 0.001）。此外，最大肾小球直径与UPCR降低≥30%独立相关（比值比：1.07，95%置信区间：1.01-1.14）。
在CKD患者中，肾小球直径与达格列净治疗开始后UPCR的早期变化独立相关。
