Effects of Paricalcitol on Renal Secondary Hyperparathyroidism and Proteinuria in Dogs With Chronic Kidney Disease.

Abstract

BACKGROUND: Renal secondary hyperparathyroidism (RHPT) is an inevitable consequence of chronic kidney disease (CKD). Paricalcitol might safely attenuate RHPT and proteinuria. HYPOTHESIS/OBJECTIVE: Paricalcitol decreases parathyroid hormone (PTH) and proteinuria in dogs with CKD. ANIMALS: Thirteen dogs with naturally acquired CKD. METHODS: Placebo-controlled clinical trial. Dogs were randomly allocated to receive a placebo or paricalcitol (14&#x2009;ng/kg/day) in a crossover design of 2, 12-week arms. Dogs were evaluated every 3&#x2009;weeks. Associations between treatment, visit, and the outcome variables were assessed using generalized estimating equations. RESULTS: PTH decreased by 22% (95% CI, 7%-35%, p&#x2009;=&#x2009;0.006) in the paricalcitol-treated dogs and increased by 18% (95% CI, 2%-37%, p&#x2009;=&#x2009;0.022) in the placebo-treated dogs with each visit. FGF-23 at 12&#x2009;weeks increased compared with baseline in the paricalcitol-treated (mean 6941&#x2009;pg/mL, 95% CI, 1781-20&#x2009;057 vs. 489&#x2009;pg/mL, 95% CI, 188-1272, p&#x2009;<&#x2009;0.001, respectively), but not in the placebo-treated dogs (696&#x2009;pg/mL, 95% CI, 316-1531 vs. 955&#x2009;pg/mL, 95% CI, 308-2963, p&#x2009;=&#x2009;0.529). Urine protein-to-creatinine ratio at 12&#x2009;weeks increased compared with baseline in the placebo-treated (0.8, 95% CI, 0.3-1.3 vs. 0.5, 95% CI, 0.2-0.9, p&#x2009;=&#x2009;0.04, respectively), but not in the paricalcitol-treated dogs (0.6, 95% CI, 0.3-0.9 vs. 1.0, 95% CI, 0.1-1.8, p&#x2009;=&#x2009;0.35). Ionized calcium was unchanged between baseline and 12&#x2009;weeks in the paricalcitol- and placebo-treated groups (1.3&#x2009;mmol/L, 95% CI, 1.29-1.35 and 1.34, 95% CI, 1.27-1.40 vs. 1.30, 95% CI, 1.25-1.35, p&#x2009;=&#x2009;0.12 and 1.28, 95% CI, 1.24-1.32, p&#x2009;=&#x2009;0.034, respectively). However, 7/13 dogs developed mild hypercalcemia. Adverse effects were not reported by the owners. CONCLUSION AND CLINICAL IMPORTANCE: Paricalcitol attenuated RHPT and stabilized renal proteinuria in dogs with CKD.