2017 ACVIM Forum Research Abstract Program

A weight gain of 37% in dogs does not appear to affect most routine markers of kidney function or GFR. Increased UPC does suggest that weight gain results in higher urinary excretion of protein as seen in humans. Additionally, CEUS was able to detect differences in blood volume and velocity of the renal medulla, which may indicate that structural and functional changes may have occurred as a result of weight gain. Further studies utilizing noninvasive markers or techniques to localize abnormalities in kidney function or injury in obese dog are warranted. Additional studies are also required to evaluate whether these changes are reversible after weight loss. Fibroblast growth factor 23 (FGF-23) is a bone-derived hormone that regulates phosphorus (P) and vitamin D metabolism. It was recently shown that dogs with chronic kidney disease (CKD) have increased FGF-23 concentrations. FGF-23 increases urinary fractional excretion of phosphorus (uFEP) in order to limit increases in serum phosphorus. The phosphaturic activity of FGF-23 is based on suppression of renal P reabsorption in the proximal tubules. Recently human studies showed that uFEP/FGF-23 ratio may reflect functional nephrons and the phosphaturic actions of FGF-23, and can be used as prognostic marker of CKD. A low uFEP/FGF-23 ratio may indicate a reduction in the number of functional nephrons and/or impaired FGF-23 signaling from Klotho (co-receptor for FGF-23) expression. The goal of this study was to evaluate whether uFEP/FGF-23 ratio reflect severity of CKD and could predict prognosis of CKD dogs. Sixteen CKD dogs were followed-up for 13 months or until death (IRIS stage 2, n = 5; stage 3, n = 11). Urinary and serum phosphorus as well as serum FGF-23 were measured at the first visit. The uFEP/FGF-23 ratio was determined in fifteen healthy dogs (mean AE SEM; 0.083 AE 0.024). Normophosphatemia (3.54 AE 0.07 mg/dL; range 2.3 to 5.4 mg/dL) was detected in all CKD dogs in stage 2 most of the times during the follow-up, and hyperphosphatemia detected in 8 out of 11 dogs in stage 3 (5.68 AE 0.23 mg/dL; range 2.5 to 16.0 mg/dL). The uFEP/FGF-23 ratio was 0.027 AE 0.014 in stage 2 CKD, and 0.006 AE 0.003 in stage 3 CKD (P = 0.0122). Serum FGF-23 concentrations were higher in stage 3 and even though FGF-23 was increased, there was no increment in phosphaturia. CKD dogs in stage 3 with lower uFEP/FGF-23 ratios had a poorer prognosis. Decreased survival was predicted when uFEP/FGF-23 ratios were less than 0.006 (survival up to 300 days). The worst prognosis occurred when uFEP/FGF-23 ratio was < 0.003 (less than 130 days survival). In conclusion, a low uFEP/FGF-23 ratio associated with normal to high serum FGF-23 concentrations supports a reduction in functional nephrons and/or impaired FGF-23 signaling from renal injury since increased FGF-23 should promote sufficient phosphaturia. Evaluation of Klotho (serum, urine, renal tissue) will be valuable to this question. Studies with larger population of dogs in various IRIS CKD stages will confirm the prognostic value of uFEP/ FGF-23 in dogs with spontaneous chronic kidney disease. Alpha-enolase, a ubiquitous, glycolytic enzyme known for catalyzing the conversion of 3-phosphoglycerate to phosphoenolpyruvate, has been implicated as a self-antigen in various autoimmune diseases. Autoantibodies in serum are capable of eliciting renal injury and ultimately can contribute to patient morbidity and mortality. Furthermore, endogenous renal alpha-enolase