Vascular calcification is an important risk factor in human chronic kidney disease (CKD) and associated with dysregulated mineral metabolism. Precipitation of calcium and phosphate starts by formation of soluble colloidal primary calciprotein particles (CPPs) which transform to crystalline secondary CPPs. Shorter duration of this transformation step (i.e. increased serum calcification propensity) is associated with increased mortality in human CKD patients. Although vascular calcification is under recognized in cats with CKD, mineral disturbances similar to those observed in human CKD are common. Plasma fibroblast growth factor 23 (FGF23) concentration is a marker of mineral disturbances in feline CKD. Here, we examined serum calcification propensity in a cross-section of cats with varying degrees of renal dysfunction, and its relationship with plasma FGF23, phosphate, total calcium, magnesium, and total protein concentrations, and calcium phosphate product.
Blood samples were prospectively collected from 5 euthyroid non-azotemic cats ≥9 years old, 12 cats with International Renal Interest Society (IRIS) stage 2 CKD, and 3 cats with IRIS stage 3 CKD, and stored at -80⁰C. Serum calcification propensity was measured with a functional assay that detects the transformation time (T50) of spherical primary CPPs to elongated secondary CPPs by a diagnostic company blinded to the clinical data (Calciscon, Nidau-Biel, Switzerland). Intact FGF23 was measured in EDTA plasma using a validated ELISA assay (Kainos Laboratories, Tokyo, Japan). Serum T50 values among the three groups were compared using one-way ANOVA with post-test for linear trend. Correlations between serum T50 and plasma FGF23, phosphate, total calcium, magnesium, and total protein concentrations, and calcium phosphate product were assessed with Spearman’s rank correlation (rs).
The mean T50 value was 250 (standard deviation [SD], 58.4) minutes in non-azotemic cats, 204 (SD, 66.5) minutes in cats with IRIS stage 2 CKD, and 119 (SD, 51.5) minutes in cats with IRIS stage 3 CKD. Mean T50 was different among groups (P = 0.037) with a significant linear trend (P = 0.011), indicating that serum calcification propensity increased in groups with worsening kidney function. Serum T50 was inversely correlated with plasma FGF23 (rs = -0.63; P = 0.003) and total protein (rs = -0.53; P = 0.017), but did not correlate significantly with plasma creatinine (rs = -0.42; P = 0.069), phosphate (rs = -0.34; P = 0.146), total calcium (rs = -0.23; P = 0.341), calcium phosphate product (rs = -0.27; P = 0.250), or magnesium (rs = 0.27; P = 0.258).
These preliminary data suggest serum of cats loses its intrinsic properties to inhibit calcification with declining renal function. The velocity with which serum calcified was inversely associated with plasma FGF23 and total protein concentrations, which may suggest that dysregulation of mineral metabolism and chronic inflammation are underlying mechanisms of soft tissue calcification in cats. Further research in a larger population of cats is needed to confirm our findings and assess the prognostic value of serum calcification propensity in cats with CKD.
Royal Veterinary College
Henk van den Broek graduated with honor from Utrecht University in 2013. After some time in first opinion small animal practice, he joined the Royal Veterinary College in London for a PhD in feline chronic kidney disease-mineral and bone disorder under supervision of Professor Jonathan Elliott and Dr Rosanne Jepson. He has recently published on hypercalcaemia and on the prognostic importance of magnesium in feline CKD.
Friday, June 15
11:15 AM – 11:30 AM
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