Chronic low-grade inflammation is a key contributor to the progression of kidney disease. The release of cytokines and other pro-inflammatory proteins may further contribute to detrimental kidney health by increasing interstitial edema and renal fibrosis. The aim of the present study was to investigate the inflammatory markers in canines who developed renal disease naturally and were diagnosed with renal disease either during life or following necropsy, as assessed by a veterinarian. RNA was isolated from canine blood obtained at necropsy and stored as bioarchived samples from ten canines with renal disease (9.6–14.7 yr) and ten controls (10.1–14.8 yr). At the time of death, the mean blood creatinine concentration and BUN were elevated in dogs with renal disease compared to control (both p < 0.01). Samples were assessed for changes in gene expression using the Canine cytokine RT² Profiler PCR Array for inflammation. There was a significant increase in C-C Motif Chemokine Ligand 16 (CCL16), C-X-C Motif Chemokine Ligand 5 (CXCL5), Interleukin 16 (IL-16), and Complement Component 5 (C5) (all p < 0.05 vs. con). In addition, there was also a statistically non-significant increase in 49 genes and a down-regulation in 35 genes from a panel of total 84 genes. Pro-inflammatory genes including CCL16, CXCL5, IL-16, and C5 can all contribute to renal inflammation and fibrosis through different signaling pathways and may lead to a progressive impairment of kidney function. Blockade of their activation may be important in ameliorating the initiation and/or the progression of renal disease.

This study used thirty-two dogs, which were assigned to a preferred period of 14 days and then assigned to one of the four treatment foods: control (containing no added betaine, no added L-carnitine), control with 0.5% added betaine (Treatment 2), control with no added betaine and 300 ppm added L-carnitine (Treatment 3), or control with 0.5% added betaine and 300 ppm added L-carnitine (Treatment 4). All treatment foods were fed for ninety days. Untargeted blood metabolomic analysis and immune response were measured at the beginning and end of the 90-day feeding trial. Feeding betaine increased single-carbon metabolites while decreasing many carnitine-containing metabolites. Feeding L-carnitine increased many carnitine metabolites, while the combination synergistically influenced the metabolome. The combination of betaine and L-carnitine increased the cytokines released in a Tru-culture system in response to stimulation while numerically decreasing their release when unstimulated. Therefore, the combination of dietary betaine and L-carnitine could have the dual positive effects of reducing cytokine stimulation, controlling inflammation during health, and providing a robust response to bacterial infection.

Background: Mature microRNAs (miRNAs) have been implicated in inflammation and fibrosis and are associated with the pathogenesis of renal dysfunction. miRNAs are single-stranded RNAs approximately 22 nucleotides in length that can posttranscriptionally modify mRNA by base-pairing with its complementary sequences leading to the silencing of mRNA. Methods: We assessed circulating levels of miRNAs in the blood of dogs that were clinically diagnosed as having chronic kidney disease (CKD) post-mortem, after the dogs had lived their full lives. Gene expression was measured using a Canine miRNA PCR array from blood samples that were collected at the natural end-of-life necropsy from dogs with CKD (2–17 yr) and control dogs (5–13.5 yr). Results: End-of-life pathology reports indicated interstitial inflammation, fibrosis, and thickening of the Bowman’s capsule. Histopathological analysis of H&E-stained renal sections taken from end-of-life samples showed a significantly higher number of healthy glomeruli as assessed morphologically in controls compared with CKD. There was a significant decline in the levels of miRNAs cfa-let-7a, cfa-let-7c, cfa-let-7f, and cfa-let-7g in dogs with CKD compared with controls. In addition, there was also a ≥1.5-fold reduction in levels of cfa-miR-93, cfa-miR-122, cfa-miR-200a, and cfa-miR-204 in CKD compared with controls (all ns). These microRNAs may have potential anti-fibrogenesis effect and are also down-regulated in rodent models and in in vitro mechanistic models of renal fibrosis, leading to increased fibrosis. There was also a down-regulation of cfa-miR-16 (−2.76 fold, ns), which is consistent with its reported role in attenuating kidney injury independent of fibrosis. Conclusions: Down-regulation of these miRNAs may be indicative of a reduction in their role in attenuating renal function, leading to impaired kidney function and possibly fibrogenesis. Importantly, the circulating miRNAs may serve as non-invasive biomarkers for impaired renal function in CKD. Nutritional interventions that upregulate selected miRNAs may serve as important targets for slowing the progression of CKD.