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.