Effects of Paricalcitol on Renal Secondary Hyperparathyroidism and Proteinuria in Dogs with CKD

Abstract: Background– Renal secondary hyperparathyroidism (RHPT) occurs in dogs with chronic kidney disease (CKD). Paricalcitol, a 2nd generation vitamin D analog may have beneficial effects including PTH reduction, proteinuria attenuation, and prolonged survival. Hypothesis/Objectives– Determine the effect of paricalcitol on RHPT and proteinuria in dogs with CKD.Animals– Thirteen dogs with naturally-acquired CKD stage 2-4. Methods– Double-blinded, placebo-controlled study. Dogs were randomly allocated to receive placebo or paricalcitol (14 ng/kg PO once daily) in a crossover design of two, twelve-weeks arms. Dogs were evaluated every 3 weeks. Associations between treatment, visit and the outcome variables were assessed using generalized estimating equations. Separate analyses were performed for each variable level for which an interaction effect was observed.Results– There was no difference in base-line creatinine of paricalcitol- and placebo-treated dogs (2.87 mg/dL, 2.25-3.48 vs. 2.81 mg/dL, 2.16-3.45, P=.603). With each visit, PTH concentrations decreased by 22% (7%-35%, P=.006) in the paricalcitol-treated dogs, and increased by 18% (2%-37%, P=.022) in the placebo-treated dogs. FGF-23 concentrations at 12 weeks increased compared to baseline in the paricalcitol-treated dogs (6941 pg/mL, 1781-20057 vs. 489 pg/mL, 188-1272, P<.001, respectively), but not in the placebo-treated dogs (696 pg/mL, 316-1531 vs. 955 pg/mL, 308-2963, P=.529). Urine protein-to-creatinine ratio at 12 weeks increased compared to baseline in the placebo-treated dogs (0.8, 0.3-1.3 vs. 0.5, 0.2-0.9, P=.040, respectively), but not in the paricalcitol-treated dogs (0.6, 0.3-0.9 vs. 1.0, 0.1-1.8, P=.351). Ionized calcium did not change between visits in both groups. Conclusions and clinical importance– Paricalcitol attenuated RHPT in dogs with CKD.