Data_Sheet_1_Evaluation of Bcl-2 as a marker for chronic kidney disease prediction in cats.docx

Chronic kidney disease (CKD) is a frequent condition in elderly cats. Bcl-2 is linked to kidney disease through the processes of apoptosis and fibrosis. The purpose of this study is to examine Bcl-2 levels in CKD and clinically healthy age-matched cats in order to evaluate the relationship between Bcl-2 levels, signalment, and blood parameters in cats with CKD. The circulating levels of Bcl-2 were determined using an immunoassay in twenty-four CKD cats and eleven clinically healthy age-matched cats by the utilization of the general linear model (GLM), Pearson correlation, principal component analysis (PCA), ROC curves, the Cox hazard model, and Kaplan–Meier survival analysis. These were all conducted in order to explore Bcl-2 levels and their connection with other variables. The Bcl-2 immunohistochemical intensity was graded in each glomerulus and tubulointerstitium. McNemar's test was performed in order to compare the expression of Bcl-2 in the two renal tissue sites. The circulating Bcl-2 of CKD cats was significantly lower than those of clinically healthy age-matched cats (P = 0.034). The presence of circulating Bcl-2 (P < 0.01) and the severity of CKD (P = 0.02) were both linked with the survival time of cats with CKD. The area under the curve (AUC) of Bcl-2 for detection of CKD was 0.723. In cats, decreased circulating Bcl-2 was associated with increased blood BUN, creatinine levels, and CKD severity. Bcl-2 protein expression was reduced in the renal tissues of CKD cats as the disease progressed, resulting in a decrease in their survival time. This study demonstrated that Bcl-2 may be effective in diagnosing feline CKD.

慢性肾病（Chronic kidney disease, CKD）是老年猫的高发病症。Bcl-2可通过细胞凋亡与纤维化过程与肾病发生发展相关联。本研究旨在检测慢性肾病猫与临床健康的同年龄对照猫的Bcl-2水平，以评估Bcl-2水平与慢性肾病猫的个体特征、血液参数之间的关联。研究人员通过免疫测定法检测了24只慢性肾病猫与11只临床健康的同年龄对照猫的循环Bcl-2水平，并运用一般线性模型（general linear model, GLM）、皮尔逊相关分析、主成分分析（principal component analysis, PCA）、受试者工作特征曲线（Receiver Operating Characteristic, ROC）、Cox风险模型及Kaplan–Meier生存分析，以探究Bcl-2水平及其与其他变量的关联。研究人员对每个肾小球与肾小管间质的Bcl-2免疫组化强度进行分级评分，并采用麦克内马尔检验（McNemar's test）比较两个肾组织位点的Bcl-2表达差异。结果显示，慢性肾病猫的循环Bcl-2水平显著低于临床健康的同年龄对照猫（P=0.034）。循环Bcl-2的存在（P<0.01）与慢性肾病严重程度（P=0.02）均与慢性肾病猫的生存时间显著相关。用于检测慢性肾病的Bcl-2的曲线下面积（area under the curve, AUC）为0.723。在猫群体中，循环Bcl-2水平降低与血液尿素氮（blood urea nitrogen, BUN）、肌酐水平升高以及慢性肾病严重程度增加呈显著正相关。随着疾病进展，慢性肾病猫肾组织中的Bcl-2蛋白表达水平降低，进而导致其生存时间缩短。本研究证实，Bcl-2或可用于猫慢性肾病的临床诊断。