ObjectiveTo review the inter-relationships between calcium, phosphorus, parathyroid hormone (PTH), parent and activated vitamin D metabolites (vitamin D, 25(OH)-vitamin D, 1,25(OH)2-vitamin D, 24,25(OH)2-vitamin D), and fibroblast growth factor-23 (FGF-23) during chronic kidney disease (CKD) in dogs and cats.Data SourcesHuman and veterinary literature.Human Data SynthesisBeneficial effects of calcitriol treatment during CKD have traditionally been attributed to regulation of PTH but new perspectives emphasize direct renoprotective actions independent of PTH and calcium. It is now apparent that calcitriol exerts an important effect on renal tubular reclamation of filtered 25(OH)-vitamin D, which may be important in maintaining adequate circulating 25(OH)-vitamin D. This in turn may be vital for important pleiotropic actions in peripheral tissues through autocrine/paracrine mechanisms that impact the health of those local tissues.Veterinary Data SynthesisLimited information is available reporting the benefit of calcitriol treatment in dogs and cats with CKD.ConclusionsA survival benefit has been shown for dogs with CKD treated with calcitriol compared to placebo. The concentrations of circulating 25(OH)-vitamin D have recently been shown to be low in people and dogs with CKD and are related to survival in people with CKD. Combination therapy for people with CKD using both parental and activated vitamin D compounds is common in human nephrology and there is a developing emphasis using combination treatment with activated vitamin D and renin-angiotensin-aldosterone-system (RAAS) inhibitors.
Background: Nephrotic syndrome (NS) develops most commonly in people with glomerular diseases associated with marked albuminuria. Hypernatremia, hypertension, and progressive renal failure are more prevalent in nephrotic than nonnephrotic human patients.Hypothesis/Objectives: Dogs with NS have higher serum cholesterol, triglyceride, and sodium concentrations, higher urine protein:creatinine ratios (UPC) and systolic blood pressure, and lower serum albumin concentrations than dogs with nonnephrotic glomerular disease (NNGD). NS is associated with membranous glomerulopathy and amyloidosis. Affected dogs are more likely to be azotemic and have shorter survival times.Animals: Two hundred and thirty-four pet dogs (78 NS dogs, 156 NNGD dogs).Methods: Multicenter retrospective case-control study comparing time-matched NS and NNGD dogs. NS was defined as the concurrent presence of hypoalbuminemia, hypercholesterolemia, proteinuria, and extravascular fluid accumulation. Signalment, clinicopathologic variables, histopathologic diagnoses, and survival time were compared between groups.Results: Age, serum albumin, chloride, calcium, phosphate, creatinine, and cholesterol concentrations, and UPC differed significantly between NS and NNGD dogs. Both groups were equally likely to be azotemic at time of diagnosis, and NS was not associated with histologic diagnosis. Median survival was significantly shorter for NS (12.5 days) versus NNGD dogs (104.5 days). When subgrouped based on serum creatinine (o or !1.5 mg/dL), survival of NS versus NNGD dogs was only significantly different in nonazotemic dogs (51 versus 605 days, respectively).Conclusions and Clinical Importance: Presence of NS is associated with poorer prognosis in dogs with nonazotemic glomerular disease. Preventing development of NS is warranted; however, specific interventions were not evaluated in this study.
BackgroundLong‐term treatment of cats with ionized hypercalcemia using alendronate has not been evaluated.Hypothesis/ObjectivesAlendronate is well tolerated in treatment of ionized hypercalcemia in cats.AnimalsA total of 12 cats with ionized hypercalcemia.MethodsProspective study of 12 cats with ionized hypercalcemia of idiopathic origin was identified by telephone and email communication with a convenience sample of consulting veterinarians. Cats were treated with alendronate at a dose of 5–20 mg per feline PO q7d. Serum ionized calcium concentration (iCa) was measured before beginning treatment with alendronate, and after 1, 3, and 6 months of treatment. Alendronate dosage was adjusted according to iCa. Evaluation included physical examination, CBC, biochemistry profile, and diagnostic imaging. The owners and referring veterinarians were questioned about any observed adverse effects. The Wilcoxon matched‐pairs signed rank test was used to compare baseline iCa to iCa at different time periods.ResultsAlendronate treatment resulted in a decrease in iCa in all 12 cats. The median percentage change in iCa was −13.2%, −15.9%, and −18.1% (range, −29.6 to +7.6; −30.5 to −1.9; −45.8 to +1.5%) at the 1, 3, and 6 month time points, respectively. Baseline iCa was significantly different from 1 month (P = .0042), 3 months (P = .0005), and 6 months (P = .0015). No adverse effects were reported for any of the cats.Conclusions and Clinical ImportanceAlendronate was well tolerated and decreased iCa in most cats for the 6‐month period of observation.
Case summaryA 14-year-old cat presented with bilateral patellar fractures and radiographically thickened tibial cortices. This cat had been treated with alendronate for 8 years prior to presentation. To remove the subjectivity of the radiographic evaluation, tibial radiographs from 35 apparently healthy geriatric cats were used for comparison. Cortical and diaphyseal thickness were measured at the proximal and distal thirds of the tibia. Our cat had increased cortical bone thickness compared to that of the control cats.Relevance and novel informationTreatment with bisphosphonates can lead to brittle bones and fractures after prolonged use in humans. This is the first description of fractures and cortical bone changes that may have been associated with prolonged bisphosphonate use in a cat. Radiographic measurements of cortical bone thickness may identify cats that are at increased risk for bone pathology secondary to prolonged alendronate use.
Gemcitabine had antitumor effects on canine TCC cells in vitro, and the combination of gemcitabine and carboplatin had synergistic activity at biologically achievable concentrations.
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