Kidney surface ablation in mice significantly increased BUN (90.9 vs 29.0 mg/dL) and E/e' (49.1 vs 25.3) compared to sham controls (p<0.05), establishing a novel model for CKD-induced HFpEF.
Does kidney surface ablation induce a CKD-HFpEF phenotype in male C57BL/6J mice?
Kidney surface ablation in mice successfully induces a CKD model with preserved renal nerves and subsequent diastolic dysfunction, providing a novel model for studying cardiorenal interactions in HFpEF.
p-value: p=<0.05
Abstract Introduction Chronic kidney disease (CKD) exacerbates heart failure through cardiorenal interactions, yet the underlying mechanisms remain unclear. Sympathoexcitatoin plays a crucial role in heart failure development. Renal injury increases the activity of afferent sensory nerves from the kidney to the sympathetic centres in the brain, and acute stimulation of these afferent renal nerves may enhance sympathetic outflow. Thus, afferent nerve input from the kidney to the brain may contribute to cardiorenal interaction. However, the widely used 5/6 nephrectomy CKD model is inadequate for studying kidney-brain neural mechanisms, as it involves the removal of one kidney and its renal nerves. Purpose This study aimed to develop a novel CKD model that preserves both kidneys and their renal nerves and to investigate its cardiac phenotype. Methods Male C57BL/6J mice were used. On Day 1, the surface of one kidney’s upper and lower poles was ablated using an electric heating wire. On Day 8, the same procedure was performed on the contralateral kidney. On Day 36, renal function and cardiovascular parameters were assessed. Results On Day 36, BUN and serum creatinine levels were significantly higher in ablated mice than in sham controls (BUN: 90.9 ± 4.7 vs. 29.0 ± 1.4 mg/dL; creatinine: 0.295 ± 0.023 vs. 0.095 ± 0.005 mg/dL; n = 6 vs. n = 4; p 0.05). Urine albumin, and the urine albumin-to-creatinine ratio (UACR) were also significantly increased in ablated mice (urine albumin: 29.3 ± 8.7 vs. 1.2 ± 0.3 μg/24 hr; UACR: 0.474 ± 0.205 vs. 0.027 ± 0.004 μg/g; n= 6 vs. 4; p 0.05). There were no significant differences in systolic blood pressure or heart rate (systolic blood pressure: 111.9 ± 2.6 vs. 104.2 ± 1.6 mmHg; heart rate: 638.5 ± 20.0 vs. 599.5 ± 23.2 bpm; n= 6 vs. 4) between the groups. Echocardiographic data showed a significant increase in E/e’ (49.1 ± 8.6 vs. 25.3 ± 1.9; n=3 vs. n=3; p 0.05), whereas left ventricular wall thickness (intraventricular septum thickness + posterior wall thickness: 1.71 ± 0.05 vs. 1.71 ± 0.21 mm), ejection fraction (72.2 ± 4.5 vs. 68.2 ± 0.7%), and E/A ratio (2.21 ± 0.18 vs. 1.70 ± 0.14) showed no significant differences. Conclusions and Perspectives This kidney surface ablation model provides a more physiologically relevant CKD model by preserving partial renal function in both kidneys. Additionally, it enables the study of CKD-induced cardiac dysfunction, as diastolic dysfunction was observed four weeks after CKD induction. Future studies will examine whether this model exacerbates heart failure when combined with heart failure models, such as a myocardial infarction model. Furthermore, renal afferent nerve denervation will help clarify the role of neurogenic renal afferent input in the pathophysiology of heart failure with concomitant CKD.
Miyamoto et al. (2025) studied Chronic kidney disease and heart failure (n=10). Kidney surface ablation vs. Sham controls was evaluated on Renal function and cardiovascular parameters (p=<0.05). Kidney surface ablation in mice significantly increased BUN (90.9 vs 29.0 mg/dL) and E/e' (49.1 vs 25.3) compared to sham controls (p<0.05), establishing a novel model for CKD-induced HFpEF.