Increased Expression of Inflammatory Genes Using RNAseq in Kidney Tissue in Felines with Renal Disease or Calcium Oxalate Stones (P09-005-19)

Inflammatory processes play an important role in the initiation and progression of kidney disease. Renal calcium oxalate stone formed from the crystal deposits in the tubular epithelial cells can increase reactive oxygen species and subsequent inflammation. We investigated the gene expression At the time of death the circulating levels of creatinine and SDMA, markers of kidney decline, were significantly higher in cats with renal disease (n = 11) or stone-forming cats (CaOx, n = 12) when compared to controls (n = 19). We identified 3 candidate genes including complement C3d receptor (CR2), MMP-7, and IKAROS family zinc finger 3, that were maximally up-regulated in renal disease with fold increases of 14.3, 13.9, and 10.9 when compared to controls (p < 0.01). Other selected inflammatory markers that were significantly increased but less than 10-fold included IL7R, TLR8, CXCR4, LCP1, IL2RB, and MSR1. The profile for maximally up-regulated genes in CaOx cats was somewhat similar when compared with those with renal disease with the exception of MMP-7. In CaOx cats the maximal up-regulation occurred in CR2, IKAROS family zinc finger 3, and L-selectin with fold increases of 33.9, 16.8, and 12.6 when compared to controls (p < 0.01). Selected inflammatory markers that were significantly increased, but less than 10-fold, included CD37, DOCK2, LCP1, CCL19, and TLR7 in CaOx compared to controls. Interestingly, there was a significant increase in Fc fragment of IgM receptor (FCMR) in both renal disease (12.4 fold) and CaOx (13.2 fold) when compared to controls. Our results identify newer immune biomarkers that are novel targets for attenuating kidney dysfunction and while there are similarities in the inflammatory genes upregulated in cats with kidney disease and stone formers, the expression profile of upregulated genes, taken as a whole, is different in both groups. These results indicate that there are somewhat different renal responses to calcium oxalate stones and renal disease which suggests the optimal anti-inflammatory nutritional therapy may be different. Hill’s Pet Nutrition, Inc.