Urinary MCP1 and Microalbumin increase prior to onset of Azotemia in mice with polycystic kidney disease.

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.

Implications of age and diet on canine cerebral cortex transcription.

Mechanisms contributing to age-related cognitive decline are poorly defined. Thus, we used canine microarrays to compare gene expression profiles of brain tissue from geriatric and young adult dogs. Cerebral cortex samples were collected from six geriatric (12-year old) and six young adult (1-year old) female beagles after being fed one of two diets (animal protein-based versus plant-protein based) for 12 months. RNA samples were hybridized to Affymetrix GeneChip Canine Genome Arrays. Statistical analyses indicated that the age had the greatest impact on gene expression, with 963 transcripts differentially expressed in geriatric dogs. Although not as robust as age, diet affected mRNA abundance of 140 transcripts. As demonstrated in aged rodents and humans, geriatric dogs had increased expression of genes associated with inflammation, stress response, and calcium homeostasis and decreased expression of genes associated with neuropeptide signaling and synaptic transmission. In addition to its existing strengths, availability of gene sequence information and commercial microarrays make the canine a powerful model for studying the effects of aging on cognitive function.