Laboratory of Renal Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Laboratory of Cellular and Molecular Bases of Renal Physiology, Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.
Am J Physiol Endocrinol Metab. 2024 Sep 1;327(3):E302-E312. doi: 10.1152/ajpendo.00237.2023. Epub 2024 Jul 17.
Acute kidney injury (AKI) is a public health concern associated with high rates of mortality, even in milder cases. One of the reasons for the difficulty in managing AKI in patients is due to its association with pre-existing comorbidities, such as diabetes. In fact, diabetes increases the susceptibility to develop more severe AKI after renal ischemia. However, the long-term effects of this association are not known. Thus, an experimental model was designed to evaluate the chronic effects of renal ischemia/reperfusion (IR) in streptozotocin (STZ)-treated mice. We focused on the glomerular and tubulointerstitial damage, as well as kidney function and metabolic profile. It was found that pre-existing diabetes may potentiate progressive kidney disease after AKI, mainly by exacerbating proinflammatory and sustaining fibrotic responses and altering renal glucose metabolism. To our knowledge, this is the first report that highlights the long-term effects of renal IR on diabetes. The findings of this study can support the management of AKI in clinical practice. This study demonstrated that early diabetes potentiates progressive kidney disease after ischemia/reperfusion (IR)-induced acute kidney injury, mainly by exacerbating pro-inflammatory and sustaining fibrotic responses and altering renal glucose metabolism. Thus, these findings will contribute to the therapeutic support of patients with type 1 diabetes with eventual renal IR intervention in clinical practice.
急性肾损伤 (AKI) 是一个公共卫生关注点，与高死亡率相关，即使在轻度病例中也是如此。在管理 AKI 患者方面存在困难的原因之一是其与预先存在的合并症有关，例如糖尿病。事实上，糖尿病会增加肾脏缺血后发生更严重 AKI 的易感性。然而，这种关联的长期影响尚不清楚。因此，设计了一个实验模型来评估链脲佐菌素 (STZ) 处理的小鼠肾缺血/再灌注 (IR) 的慢性影响。我们专注于肾小球和肾小管间质损伤，以及肾功能和代谢特征。结果发现，预先存在的糖尿病可能会加剧 AKI 后的进行性肾病，主要是通过加重促炎和持续纤维化反应以及改变肾脏葡萄糖代谢。据我们所知，这是第一项强调肾 IR 对糖尿病的长期影响的报告。本研究结果可为临床实践中 AKI 的管理提供支持。本研究表明，早期糖尿病会加剧缺血/再灌注 (IR) 诱导的急性肾损伤后的进行性肾病，主要是通过加重促炎和持续纤维化反应以及改变肾脏葡萄糖代谢。因此，这些发现将有助于为 1 型糖尿病患者提供治疗支持，并在临床实践中对最终发生肾 IR 的患者进行干预。
