Urinary cytokine levels in apparently healthy cats and cats with chronic kidney disease

Abstract

Chronic kidney disease (CKD) is a common cause of illness and death in cats. The hallmark of CKD in cats is chronic tubulointerstitial nephritis, and inflammation contributes to the progression of renal fibrosis. However, at present, it is difficult to assess directly the degree of intra-renal inflammation without renal biopsy. Measurement of inflammatory cytokine levels in urine may provide a non-invasive means of assessing intra-renal inflammation. Urine cytokine levels (urine cytokine/urine creatinine ratio) were measured in 18 healthy cats and 26 cats with CKD. When urine cytokine levels in healthy and CKD cats were compared, we found significantly higher levels of IL-8 and transforming growth factor-β1 (TGF-β1) in urine of CKD cats, along with significantly lower vascular endothelial growth factor (VEGF) levels. A significant positive correlation between serum creatinine and TGF-β1 levels was found in CKD cats. Urinary cytokine measurement may, potentially, be a useful means of assessing intra-renal inflammation, fibrosis and vascular health in cats with CKD.

Safety and efficacy of intravenous infusion of allogeneic cryopreserved mesenchymal stem cells for treatment of chronic kidney disease in cats: results of three sequential pilot studies

“…Urine cytokine concentrations were determined using commercial ELISA kits, as we have described recently [31]. Briefly, urine concentrations of interleukin (IL)-6, IL-8, and IL-10 were measured using feline specific ELISA kits (R&D Systems), while monocyte chemoattractant protein 1 (MCP-1) and vascular endothelial growth factor (VEGF) were measured using commercial canine MCP-1 and VEGF kits respectively (R&D Systems).…”

“…All reported cytokine concentrations were normalized for differences in urine concentration as a urine cytokine-to-urine creatinine ratio. In order to maximize cytokine yield in the urine samples, additional sample processing steps were performed as previously described prior to running the IL-8, MCP-1, and VEGF ELISA kits [31]. …”

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

“…107,108 However, conflicting studies evaluating active rather than total urinary TGF-β1 found no significant difference between non-azotemic geriatric cats, nonazotemic cats that progressed to develop azotemia and azotemic cats. However, there was a trend towards increasing active urinary TGF-β in cats that developed azotemia and were monitored longitudinally.…”

“…No significant difference in MCP-1:creatinine ratio could be detected although IL8: creatinine ratio were significantly higher in cats with CKD than control cats. 107 A shortfall of these studies is that histopathology was not routinely available although in other species studies support that the correlation between urinary cytokine levels and renal inflammation is strong. 110 Transglutaminase 2 (TG-2) has recently been investigated in cats.…”

Evaluation of serum cytokines in cats with and without degenerative joint disease and associated pain

“…Cytokines and chemokines are typically produced and consumed locally, and detection of increased concentrations in peripheral blood would likely reflect much higher concentrations at the sites of release. An additional limitation in the use of serum is the contribution to cytokine load from comorbid conditions including age (Greene and Loeser, 2015), obesity (Thijssen et al, 2015), and chronic kidney disease (Habenicht et al, 2013). While we evaluated the relationship between measured cytokine concentrations and age, body condition, and the presence or absence of chronic kidney disease and found few positive associations, each likely contributes to the overall circulating concentration of cytokines in these cats.…”