Selected Research Abstracts
Journal of Veterinary Internal Medicine, Article: pp. 1307–1313 | Abstract, Volume 20, Issue 6 (November 2006)
Comparison of the Effects of Daily and Intermittent-Dose Calcitriol on Serum Parathyroid Hormone and Ionized Calcium Concentrations in Normal Cats and Cats with Chronic Renal Failure
Roger A. Hostutler, Stephen P. DiBartola, Dennis J. Chew, Larry A. Nagode, Patricia A. Schenck, Päivi J. Rajala-Schultz, and W. Tod Drost
Background: Chronic renal failure is complicated by secondary hyperparathyroidism, which traditionally has been controlled by dietary restriction of phosphorus and administration of phosphorus binders. Early treatment of patients with chronic renal failure with calcitriol may be indicated because once established, parathyroid gland hyperplasia does not readily resolve with therapy.
Hypothesis: Daily and intermittent dosing of calcitriol will decrease plasma parathyroid hormone concentration in normal cats and cats with chronic renal failure without causing ionized hypercalcemia.
Animals: Ten normal cats; 10 cats with chronic renal failure.
Methods: Phase 1 was daily calcitriol administration (2.5 ng/kg PO q24h) for 14 days. Phase 2 was intermittent calcitriol administration (8.75 ng/kg PO q84h) for 14 days. A 7-day washout period separated phases 1 and 2. Before each phase, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured. On days 1, 2, and 3 of both phases, serum ionized calcium concentrations were measured. On the last day of both phases, calcitriol, parathyroid hormone, and ionized calcium concentrations were measured 0, 2, 4, and 6 hours after calcitriol administration.
Results: Overall, serum parathyroid hormone concentrations were significantly higher in cats with chronic renal failure than in normal cats (P = .022), but serum parathyroid hormone concentrations for both normal cats and cats with chronic renal failure were not significantly different before and after 14 days of treatment with calcitriol, regardless of whether calcitriol was administered daily or intermittently. Adverse effects of calcitriol administration (specifically ionized hypercalcemia) were not seen in either feline group during either phase of the study over the 3-day evaluation after calcitriol administration was initiated.
Conclusions and Clinical Importance: At the dosages used, calcitriol treatment did not result in significant differences in serum parathyroid hormone concentrations before and after treatment in both normal cats and cats with chronic renal failure. With these dosages, adverse affects of calcitriol administration were not seen. Potential reasons for lack of apparent effect include small sample size, insufficient duration of study, insufficient dosage of calcitriol, problems with formulation or administration of calcitriol, and variable gastrointestinal absorption of calcitriol.
From the Morris Animal Foundation Web Site.
99CA-037: “"Clinical Benefit of Calcitriol in Canine Chronic Renal Failure"
University of Minnesota, Dr. David J. Polzin (David J. Polzin, DVM, PhD, DACVIM, Professor of Veterinary Internal Medicine)
Chronic kidney failure is a common disease, affecting about 10 percent of dogs over the age of 12. Clinical signs include lethargy, lack of appetite, vomiting, weight loss, and excessive thirst and urination. Kidney failure usually leads to death. The mainstay of therapy is dietary modification, but this isn't always successful because of the dogs lack of appetite. Other treatments, including kidney transplant, are often cost prohibitive. Deficiency of calcitriol, a hormone produced by the kidneys, may contribute to the disease. The investigators are studying whether calcitriol replacement therapy alleviates the clinical signs in dogs with kidney failure. The results may offer a new treatment option that will extend the dogs life and the quality of life.
This study examined the use of calcitriol therapy for dogs with chronic kidney disease. Researchers determined that calcitriol is effective in stabilizing the renal function in dogs with this disease, leading to prolonged survival. Although previous, uncontrolled studies had indicated that this type of therapy could also improve appetite, increase physical activity or improve interactions between pet and owners, this controlled study did not support those results. However, since calcitriol therapy was found to be safe and effective in stabilizing renal function, the investigators recommend using it to treat dogs with kidney disease.
99FE-14, University of Minnesota, Dr. David J. Polzin (David J. Polzin, DVM, PhD, DACVIM, Professor of Veterinary Internal Medicine)
“Clinical Benefit of Calcitriol in Feline Chronic Renal Failure”
Description: Chronic kidney failure is one of the most common diseases affecting older cats, with about 10 percent of cats over the age of 10 and 30 percent of those over the age of 15 developing the disease. Symptoms include lethargy, vomiting, weight loss, and excessive thirst and urination. The disease typically leads to death. A deficiency in calcitriol, a hormone produced by the kidneys, appears to contribute to the disease's development. The investigators are studying whether calcitriol replacement therapy in cats with chronic kidney failure will improve the cat's quality of life and prolong its survival.
Accomplishment: In contrast to previously completed uncontrolled studies of chronic kidney disease in cats, the investigators found, through their controlled study, that calcitriol doesn't appear to improve appetite, physical activity or pet-owner interactions. In addition, they found no evidence that this type of therapy alters the course of kidney disease in cats. Although calcitriol appears to have no long-term adverse effects in cats, investigators recommend against its use given its expense and apparent lack of therapeutic effectiveness. However, because the drug was tested in cats with early stage disease, investigators stress that a follow-up study would be appropriate to evaluate whether calcitriol therapy may effectively impact the outcome of the disease in the long-term.
Editor's Note: The above is from a summary of Dr. Polzin's work on the Morris Animal Foundation web site. I don't know if it has yet been published in a peer-reviewed journal.
1: Vet Clin North Am Small Anim Pract 1996 Nov;26(6):1293-330
Benefits of calcitriol therapy and serum phosphorus control in dogs and cats with chronic renal failure. Both are essential to prevent of suppress toxic hyperparathyroidism.
Nagode LA, Chew DJ, Podell M. Department of Veterinary Biosciences, Ohio State University, Columbus, USA.
Daily oral calcitriol at low doses is safe and effective in the control of renal secondary hyperparathyroidism in dogs and cats. Low doses of calcitriol are most effective when started early in uremia before the advanced stages of renal secondary hyperparathyroidism. At early stages calcitriol both diminishes PTH synthesis in the parathyroid cells present and prevents the hyperplasia that, if unchecked, results in the most extensive an difficult-to-control hyperparathyroidism. The salutary effects on the dog's or cat's sense of well being, appetite, activity, strength, and lifespan as reported by the veterinarians of our survey are attributed primarily to keeping PTH levels below a toxic threshold. Additionally, some of the benefits achieved by calcitriol are likely a direct consequence of calcitriol interacting with the vitamin D receptor in a wide variety of tissues throughout the body. Phosphorus restriction through a combination of diet and intestinal phosphate binders is important to allow calcitriol therapy to successfully lower PTH levels, but it likely has no direct effects that are independent of interactions involving calcitriol. Phosphorus restriction is also important to minimize chances for adverse tissue mineralization. Calcitriol therapy can be considered for treatment of chronic renal failure after serum phosphorus has been decreased to less than 6.0 mg/dL in patients in whom it was initially elevated. Calcitriol supplementation to dogs and cats with chronic renal failure makes good endocrinologic sense. Calcitriol deficits cause increased PTH and, as these two hormones are designed to maintain calcium and phosphorus homeostasis, the PTH increase is initially adaptive. One of the important effects of PTH is to stimulate additional calcitriol formation as a powerful means to raise blood calcium through increased calcium absorption from the diet. With too great an increase in PTH, however, its effects become harmful to many tissues due to the widespread distribution of the PTH receptor in many cell types that are likely normally responsive only to the paracrine PTH-related peptide that shares the PTH receptor. Exogenous supplemental calcitriol administration allows concentrations of calcitriol in the bloodstream to remain normal without the toxic consequences of excessive PTH secretion that would otherwise be provoked. Studies involving young dogs with subtotal nephrectomy may not parallel those on older dogs and cats with spontaneous chronic renal failure. In particular, higher doses are needed to effect PTH change in these young dogs than we have found necessary for older dogs and cats. Because survey participants agreed most strongly with the idea that their calcitriol-treated dogs and cats were living longer than comparably uremic animals they had treated previously, further studies to evaluate the ability of calcitriol to retard the progression of renal lesions and loss of excretory renal function seem warranted. Additional studies to document the beneficial effects of calcitriol on the many organs adversely affected by excess PTH during uremia are also needed because findings thoroughly documented and proven in humans and rats may not always extrapolate to dogs and cats.
PMID: 8911021 [PubMed - indexed for MEDLINE]
chronic renal failure: calcium homeostasis in 80 cases diagnosed between 1992
Eighty cats with chronic renal failure (CRF) were evaluated in a prospective study to investigate the prevalence and aetiopathogenesis of renal secondary hyperparathyroidism (RHPTH), using routine plasma biochemistry and assays of parathyroid hormone (PTH), blood ionised calcium and 1,25 dihydroxycholecalciferol (1,25[OH]2D3). Hyperparathyroidism was a frequent sequela of CRF, affecting 84 per cent of cats with CRF, the severity and prevalence of RHPTH increasing with the degree of renal dysfunction. Compared with an age-matched control population, plasma concentrations of phosphate and PTH were significantly higher and 1,25(OH)2D3 concentrations were significantly lower in the two groups of cats presenting with clinical signs of CRF. Significant ionised hypocalcaemia was present only in cats with end-stage renal failure. However, a number of cats were hyperparathyroid in the absence of abnormalities in the parameters of calcium homeostasis measured in this study. There was a significant correlation between plasma phosphate and PTH concentrations.
PMID: 9551377 [PubMed - indexed for MEDLINE]