Supplementary Material for: Histological Evidence of Diabetic Kidney Disease Precede Clinical Diagnosis

<b><i>Background:</i></b> In the absence of a histological diagnosis, persistent albuminuria is globally accepted as the main diagnostic criteria for diabetic kidney disease (DKD). <b><i>Methods:</i></b> In the present retrospective study, we evaluated data from an Italian cohort of 42 deceased diabetic donors (mainly with type 2 diabetes). Using the kidney biopsies obtained at the time of donation to evaluate single or double allocation based on Karpinski score, we determined the prevalence of histological lesions attributable to diabetes. <b><i>Results:</i></b> All 42 donors presented with proteinuria in the normal range and an estimated glomerular filtration rate (eGFR) (chronic kidney disease [CKD]-EPI) &gt;60 mL/min/1.73 m². A kidney biopsy was available for 36 patients; of these, one was not interpretable and 32 showed histopathological lesions consistent with DKD and encompassing all histological classes. Thus, we found a relatively high proportion of histologically proven DKD that had been clinically undiagnosed, as none of the patient had significant proteinuria and eGFR &lt;60 mL/min/1.73 m². <b><i>Conclusions:</i></b> The data we present here support the need to implement routine kidney biopsies in normoalbuminuric diabetic subjects in the early stages of CKD. Such strategy may help to improve risk stratification in diabetic patients and guide therapeutic decisions during the early stages of the disease.

**背景**：在缺乏组织病理学诊断的前提下，持续性白蛋白尿被全球学界公认为糖尿病肾病（Diabetic Kidney Disease, DKD）的主要诊断标准。
**方法**：本回顾性研究纳入意大利队列中42名已故糖尿病供体（以2型糖尿病患者为主）的临床数据。借助捐献时获取的肾脏活检标本，基于卡平斯基（Karpinski）评分评估单供肾或双供肾分配方案，本研究明确了糖尿病相关组织病理学病变的患病率。
**结果**：42名供体均表现为正常范围蛋白尿，且估算肾小球滤过率（estimated glomerular filtration rate, eGFR，基于慢性肾脏病流行病学合作研究（Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI）公式）＞60 mL/min/1.73 m²。其中36名患者留存有肾脏活检标本；在这36例中，1例活检结果无法判读，剩余32例均存在符合糖尿病肾病的组织病理学病变，且覆盖所有组织病理学分级。由此可见，本研究发现了占比相对较高的经组织病理学证实但临床未被诊断的糖尿病肾病病例——所有患者均未出现显著蛋白尿，且eGFR均不低于60 mL/min/1.73 m²。
**结论**：本研究数据证实，针对慢性肾脏病早期阶段的正常白蛋白尿糖尿病患者，应常规开展肾脏活检。该策略有助于优化糖尿病患者的风险分层，并为疾病早期阶段的治疗决策提供科学指导。