Renal secondary hyperparathyroidismis a metabolic disorder that affects about 75% of dogs and 84% of cats with chronic kidney disease (CKD). Numerous factors are implicated in the pathogenesis of this endocrine abnormality (Fig. 1): retention of phosphorus secondary to a decrease in glomerular filtration rate and reduced synthesis of 1,25-(OH)2D constitute the initial stimulus to increase the production and secretion of parathyroid hormone (PTH). In the early stages this mechanism is effective in promoting the renal excretion of phosphorus and increasing the circulating levels of calcitriol and ionised calcium; however, later, with the progressive loss of functional kidney tissue and the worsening hyperphosphataemia this mechanism is no longer sufficient to maintain calcium-phosphorus homeostasis. In advanced stages, although the circulating levels of PTH remain persistently raised there is severe hyperphosphataemia aggravated by reduced renal production of calcitriol. The prevalence of renal secondary hyperparathyroidism is especially high (>96%) in the most advanced stages of renal failure (IRIS stage 3-4), but increased secretion of PTH can also occur in the early phases (IRIS stage 1), when the serum concentrations of calcium and phosphorus are still normal.
Fig. 1. Pathogenesis of renal secondary hyperparathyroidism. (From: Rijnberk A, Kooistra HS. Clinical Endocrinology of Dogs and Cats, 2010; 2nd edition Schlutesche)
CLINICAL MANIFESTATIONS
As already mentioned, the secretion of PTH can occur in dogs and cats even in the initial stages of kidney disease (IRIS stage 1); however, the clinical signs of renal secondary hyperparathyroidism develop only if the disorder persists for a long time. Alongside the classical signs of renal failure (polyuria/polydipsia, anorexia, vomiting, and depression) there may be skeletal alterations as a result of bone demineralisation which, in the most severe cases, evolve into fibrous osteodystrophy. In adult animals the skull is the bone segment most affected, while the volume of the other bones is not usually modified. As a result of bone reabsorption, the mandible may become so demineralised as to become mobile, a feature giving rise to the name “rubber jaw” (Fig. 2).
If the renal failure develops in young subjects, before maturation of the skeleton has been completed, the process of bone repair by the connective tissue can exceed the reabsorption with a consequent increase in the volume of the bone (hyperostotic osteodystrophy). The harmful effects of hyperparathyroidism also extend to other organs and systems: other clinical signs that can be found include weakness, lethargy, anorexia and a predisposition to the development of infections because of a state of immunodepression. The excess of PTH also promotes nephrocalcinosis and a consequent worsening of the kidney disease.
CONTROL OF RENAL SECONDARY HYPERPARATHYROIDISM
The aim of treatment is to lower plasma concentrations of PTH to below a harmful level in order to improve the survival and quality of life of the animal. The most important step in the prevention and treatment of osteodystrophy is restricting the amount of phosphorus in the diet. Ideally, the concentration of phosphorus in the blood should be below 4.5 mg/dl in dogs with IRIS stage 2 disease, below 5 mg/dl in those in IRIS stage 3, and below 6 mg/dl in dogs in IRIS stage 4. The diets designed for animals with kidney disease usually have a phosphorus content of less than 75% that in normal maintenance diets and are sufficient to normalise the serum levels of phosphorus in all patients with IRIS stage 2 disease and in most of those with IRIS stage 3. In contrast, dietary therapy alone is not sufficient in subjects with IRIS stage 4; in these cases, in addition to the diet, substances able to chelate the phosphorus (preferably aluminium hydroxide) in the bowel must be given.
Besides the limitation of dietary phosphorus, recent studies indicate that benefit can be obtained from the administration of calcitriol, above all in dogs with stage 3 or 4 kidney disease. In such patients treatment with calcitriol has been demonstrated to prolong the survival and improve the quality of life of the treated animals; the same results had already been observed in humans with CKD. Treatment with calcitriol in these subjects is also indicated when the levels of PTH are not raised. However, it still remains to be determined whether early calcitriol treatment in dogs with stage 1 or 2 kidney disease is useful in preventing the onset of secondary hyperparathyroidism and improving its prognosis.
Supplementation with calcitriol can only be initiated if the blood phosphate level is below 6 mg/dl and the product of calcium x phosphorus is less than 60. The starting dose of calcitriol is 2.5 ng/kg per os every 24 hours. The aim of treatment is to maintain the levels of circulating calcium, phosphorus and PTH within the reference ranges. These parameters must initially be monitored every 2-4 weeks until the optimal dose is reached. Subsequently the controls can be performed every 3-6 months on the basis of the patient’s clinical state.
As regards cats with kidney disease, there is currently insufficient data to state that supplementation with calcitriol has beneficial clinical effects.
Suggested readings
- Cortadellas O. et al: Calcium and phosphorus homeostasis in dogs with spontaneous chronic kidney disease at different stages of severity. J vet Intern Med, 24, (1), 2010.
- Polzin J.D.: Chronic Kidney Disease. In: Ettinger S.J., Feldman E.C.: Textbook of Veterinary Internal Medicine, VII edizione Elsevier Saunders, pg. 1990-2021, 2010.
- Polzin D.J. et al: Calcitriol. In: Bonagura J.D., Twedt D.C. : Kirk’s Current Veterinary Therapy XIV, Sounders Elsevier, pg. 892-895, 2009.
- Tryfonidou M.A., Hazewinkel H.A.W. : Calciotropic Hormones. In: Kooistra H. S.: Clinical Endocrinolgy of Dogs and Cats, II edizione Schlutesche, pg. 253-295, 2010.