Kirby Naomi A, Stepanek Aaron M, Vernet Andyna, Schmidt Sarah M, Schultz Carrie L, Parry Nicola Ma, Niemi Steven M, Fox James G, Brown Diane E
Center for Comparative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Purina LabDiet, St Louis, Missouri, USA.
Comp Med. 2014 Apr;64(2):99-105.
Urinary biomarkers may offer a more sensitive and less invasive means to monitor kidney disease than traditional blood chemistry biomarkers such as creatinine. CD1(pcy/pcy) (pcy) mice have a slowly progressive disease phenotype that resembles human autosomal dominant polycystic kidney disease with renal cyst formation and inflammation. Previous reports suggest that dietary protein restriction may slow disease progression in mice and humans with polycystic kidney disease. Accordingly, we fed pcy mice either a standard chow (22.5% protein) or a protein-restricted (11.5% soy-based protein) diet from weaning until 34 wk of age. Every 6 wk we measured markers of kidney disease, including serum creatinine, BUN, and serum albumin as well as urinary monocyte chemoattractant protein 1 (MCP1), microalbumin, and specific gravity. Progression of kidney disease was equivalent for both diet groups despite dietary protein restriction. Urinary biomarkers proved useful for early detection of disease, in that urinary microalbumin was elevated as early as 22 wk of age and urinary MCP1 was increased by 28 wk of age, whereas increases in serum creatinine and BUN were detected later (at 34 wk of age) in both diet groups. Thus, urinary microalbumin and MCP1 analyses provided earlier, noninvasive indicators for detection of kidney disease and disease progression in pcy mice than did serum creatinine and BUN.
与传统的血液化学生物标志物(如肌酐)相比,尿液生物标志物可能为监测肾脏疾病提供一种更敏感且侵入性更小的方法。CD1(pcy/pcy)(pcy)小鼠具有缓慢进展的疾病表型,类似于人类常染色体显性多囊肾病,伴有肾囊肿形成和炎症。先前的报告表明,饮食蛋白质限制可能会减缓多囊肾病小鼠和人类的疾病进展。因此,我们从断奶到34周龄给pcy小鼠喂食标准饲料(22.5%蛋白质)或蛋白质限制(11.5%大豆蛋白)饮食。每6周我们测量肾脏疾病标志物,包括血清肌酐、血尿素氮和血清白蛋白以及尿单核细胞趋化蛋白1(MCP1)、微量白蛋白和比重。尽管饮食蛋白质受到限制,但两个饮食组的肾脏疾病进展情况相当。尿液生物标志物被证明对疾病的早期检测有用,因为尿微量白蛋白早在22周龄时就升高了,尿MCP1在28周龄时增加,而血清肌酐和血尿素氮的增加在两个饮食组中都在较晚的时候(34周龄)才被检测到。因此,与血清肌酐和血尿素氮相比,尿微量白蛋白和MCP1分析为检测pcy小鼠的肾脏疾病和疾病进展提供了更早的非侵入性指标。