Supplementary Material for: Exercise intervention in patients with metabolic syndrome and renal disease: a prospective study (EXRED)

Introduction: In patients with chronic kidney disease (CKD) of diverse causes, obesity and metabolic syndrome (MS) accelerate disease progression. Therapeutic exercise could be effective in treating obesity and MS in patients with CKD. However, the evidence in this area is limited. The aim of this research is to evaluate the effect of an individualized exercise program on major metabolic and renal outcomes in patients with CKD, obesity and MS.

Methods: This was an interventional exploratory study that included patients with established CKD - estimated glomerular filtration rate (eGFR) ≥ 30 ml/min, obesity and MS treated by therapeutic exercise (aerobic and resistance) for 6 months. We evaluated changes in renal outcomes - measured glomerular filtration rate (mGFR) with iohexol-DBS and albuminuria, and metabolic outcomes - weight and MS trait. Biochemical, anthropometric and renal function were performed every 3 months.

Results: Forty patients were evaluated. All were overweight or obese, mGFR was 58 ± 20 ml/min and urine albumin-creatinine ratio (UACR) 256 mg/g [IQR: 38-774]. Based on weight reduction (>5%), patients were classified as “responders” (n=30) and “non-responders” (n=10). Responders had a major reduction in body mass index (BMI) from 35 ± 4 to 31 ± 4 Kg/m² (p<0.001), triglycerides, HbA1c, systolic and diastolic blood pressure and UACR from 222 [20 – 610] to 89 [17 – 413] mg/g (p<0.01), whereas mGFR diminished (≥7%) in half of them and remained stable in the other half. Non-responders experienced no changes. No major side effects were observed.

Conclusion: In patients with CKD, obesity and MS, exercise is an effective treatment to reduce weight, MS traits and albuminuria. Changes in mGFR are heterogeneous. Understanding the impact of weight reduction on glomerular filtration rate (GFR) changes is crucial in CKD. The role of exercise in Nephrological Care deserves further attention. The study trial registration number is NCT06576518.

引言：针对多种病因所致慢性肾脏病（chronic kidney disease, CKD）患者，肥胖与代谢综合征（metabolic syndrome, MS）会加速疾病进展。治疗性运动或可有效改善CKD患者的肥胖与代谢综合征，但当前该领域的相关证据仍较为有限。本研究旨在评估个体化运动方案对合并肥胖与代谢综合征的CKD患者主要代谢及肾脏结局的影响。

方法：本研究为探索性干预研究，纳入确诊慢性肾脏病、估算肾小球滤过率（estimated glomerular filtration rate, eGFR）≥30 ml/min且合并肥胖与代谢综合征的患者，予以为期6个月的治疗性运动（有氧训练联合抗阻训练）干预。本研究评估的肾脏结局指标包括：采用碘海醇-DBS法检测的实测肾小球滤过率（measured glomerular filtration rate, mGFR）与白蛋白尿；代谢结局指标包括体重与代谢综合征特征。每3个月完成一次生化检测、人体测量学评估及肾功能检测。

结果：本研究共纳入40例患者进行评估。所有患者均存在超重或肥胖，基线实测肾小球滤过率为58±20 ml/min，尿白蛋白肌酐比（urine albumin-creatinine ratio, UACR）为256 mg/g [四分位间距：38~774]。根据体重降幅是否＞5%，将患者分为应答组（n=30）与无应答组（n=10）。应答组的体重指数（body mass index, BMI）从35±4 kg/m²显著降至31±4 kg/m²（p<0.001），甘油三酯、糖化血红蛋白（HbA1c）、收缩压、舒张压及UACR均显著改善，其中UACR从222 [20~610] mg/g降至89 [17~413] mg/g（p<0.01）；但该组中有半数患者的实测肾小球滤过率下降≥7%，其余半数则保持稳定。无应答组的各项指标均无显著变化。本研究未观察到严重不良反应。

结论：对于合并肥胖与代谢综合征的慢性肾脏病患者，治疗性运动可有效减轻体重、改善代谢综合征特征并降低白蛋白尿水平。实测肾小球滤过率的变化存在异质性。明确体重减轻对慢性肾脏病患者肾小球滤过率（glomerular filtration rate, GFR）变化的影响至关重要。治疗性运动在肾脏病诊疗中的作用值得进一步关注。本研究的临床试验注册号为NCT06576518。