Department of Nephrology and Hypertension, University Hospital Erlangen Friedrich-Alexander University Erlangen-Nürnberg (FAU), Ulmenweg 18, 91054, Erlangen, Germany.
Department of Cardiology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnnberg (FAU), Ulmenweg 18, 91054, Erlangen, Germany.
Cardiovasc Diabetol. 2024 May 29;23(1):184. doi: 10.1186/s12933-024-02223-0.
Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether the initial decline of renal function with SGLT2 inhibitor treatment is related to vascular changes in the systemic circulation.
We measured GFR (mGFR) and estimated GFR (eGFR) in 65 patients with type 2 diabetes (T2D) at baseline and after 12 weeks of treatment randomized either to a combination of empagliflozin and linagliptin (SGLT2 inhibitor based treatment group) (n = 34) or metformin and insulin (non-SGLT2 inhibitor based treatment group) (n = 31). mGFR was measured using the gold standard clearance technique by constant infusion of inulin. In addition to blood pressure (BP), we measured pulse wave velocity (PWV) under standardized conditions reflecting vascular compliance of large arteries, as PWV is considered to be one of the most reliable vascular parameter of cardiovascular (CV) prognosis.
Both mGFR and eGFR decreased significantly after initiating treatment, but no correlation was found between change in mGFR and change in eGFR in either treatment group (SGLT2 inhibitor based treatment group: r=-0.148, p = 0.404; non-SGLT2 inhibitor based treatment group: r = 0.138, p = 0.460). Noticeably, change in mGFR correlated with change in PWV (r = 0.476, p = 0.005) in the SGLT2 inhibitor based treatment group only and remained significant after adjustment for the change in systolic BP and the change in heart rate (r = 0.422, p = 0.018). No such correlation was observed between the change in eGFR and the change in PWV in either treatment group.
Our main finding is that after initiating a SGLT2 inhibitor based therapy an exaggerated decline in mGFR was related with improved vascular compliance of large arteries reflecting the pharmacologic effects of SGLT2 inhibitor in the renal and systemic vascular bed. Second, in a single patient with T2D, eGFR may not be an appropriate parameter to assess the true change of renal function after receiving SGLT2 inhibitor based therapy.
clinicaltrials.gov (NCT02752113).
钠-葡萄糖共转运蛋白 2（SGLT2）抑制剂的使用常导致肾小球滤过率（GFR）的初始下降。本研究旨在探讨 SGLT2 抑制剂治疗引起的肾功能初始下降是否与全身循环中的血管变化有关。
我们在 65 例 2 型糖尿病（T2D）患者中测量了基线时和随机接受恩格列净和利拉利汀（SGLT2 抑制剂治疗组）（n=34）或二甲双胍和胰岛素（非 SGLT2 抑制剂治疗组）（n=31）治疗 12 周后的肾小球滤过率（mGFR）和估算肾小球滤过率（eGFR）。mGFR 通过持续输注胰岛素的金标准清除技术测量。除血压（BP）外，我们还在标准化条件下测量脉搏波速度（PWV），以反映大动脉的血管顺应性，因为 PWV 被认为是心血管（CV）预后最可靠的血管参数之一。
两组患者在开始治疗后 mGFR 和 eGFR 均显著下降，但两组患者 mGFR 的变化与 eGFR 的变化均无相关性（SGLT2 抑制剂治疗组：r=-0.148，p=0.404；非 SGLT2 抑制剂治疗组：r=-0.138，p=0.460）。值得注意的是，SGLT2 抑制剂治疗组中 mGFR 的变化与 PWV 的变化相关（r=0.476，p=0.005），且在校正收缩压变化和心率变化后仍有统计学意义（r=0.422，p=0.018）。两组患者 eGFR 的变化与 PWV 的变化均无相关性。
我们的主要发现是，开始 SGLT2 抑制剂治疗后，mGFR 过度下降与大血管顺应性改善有关，反映了 SGLT2 抑制剂在肾脏和全身血管床的药理作用。其次，在单一的 T2D 患者中，eGFR 可能不是评估接受 SGLT2 抑制剂治疗后肾功能真实变化的合适参数。
clinicaltrials.gov（NCT02752113）。
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