Read the French translation: Comment Traiter un Chat Hyperthyroidien en Insuffisance Rénale Chronique?
Renal function is profoundly influenced by thyroid status. In cats, several studies have shown a marked decline of renal function after treatment of hyperthyroidism. This has been documented with all treatments routinely available for treatment of feline hyperthyroidism (medical, surgical, 131I).
Physiological Interactions Between Thyroid Hormones and Renal Function
Through their ino- and chronotropic effects, excessive thyroid hormone concentrations can lead to an increased cardiac output. Further, hyperthyroidism diminishes peripheral vascular resistance by dilating arterioles of the peripheral circulation. The increased glomerular filtration rate (GFR) associated with hyperthyroid states is thought to result from the increased cardiac output and intrarenal vasodilatation and leads to a decline in BUN and serum creatinine concentrations.
Considerations and Clinical Implications in Hyperthyroid Cats
It is important to underline that chronic kidney disease (CKD) and hyperthyroidism are both frequently encountered diseases in geriatric cats. Therefore, finding both diseases in one cat is not uncommon. Also, clinical signs of both diseases can overlap. Renal function will decline after treatment of hyperthyroidism in cats. This can unmask renal disease in some cats. Decreased muscle mass associated with emaciation and therefore decreased production of creatinine can contribute to the declined serum creatinine concentrations observed in untreated hyperthyroid cats. The presence of a hyperthyroid state could contribute to the development or progression of CKD. Systemic hypertension can lead to intraglomerular hypertension, hyperfiltration and contribute to the development of glomerulosclerosis.
In the study of Adams et al. (1997), 9 out of 22 hyperthyroid cats had concurrent CKD at presentation. Another study on a larger number of cases (n=167) reported that 14% of hyperthyroid cats had pre-existing renal disease. Further, approximately 30% of non-azotemic hyperthyroid cats develop azotemia after therapy of hyperthyroidism.
Assessment of complete blood count, chemistry, urinalysis and blood pressure are important in hyperthyroid cats prior to treatment, mostly as part as a global medical evaluation of a geriatric patient. Medical, surgical and 131I therapy are available and effective in the treatment of hyperthyroidism. Thyroidectomy and 131I are considered definitive and irreversible treatments. Daily oral administration of methimazole (MMI) is reversible.
Clinicians can be confronted with 2 different scenarios concerning azotemic hyperthyroid cats. First, the presence of pre-existing azotemia in an untreated hyperthyroid cat, second, the development of azotemia after hyperthyroid treatment in an initially non-azotemic cat. These 2 possibilities will be discussed separately, and obviously appropriate management of CKD is mandatory in both scenarios.
Pre-Existing Azotemia in a Newly Diagnosed Hyperthyroid Cat
First, in such a case, the diagnosis of hyperthyroidism can be somewhat complicated by a decline in thyroid hormones (euthyroid sickness) within the reference range. Second, given the further decline in GFR to be expected after resolution of the hyperthyroid state, it is important to start an azotemic hyperthyroid cat with a reversible anti-thyroid therapy (trial therapy). Methimazole or carbimazole are used (orally or transdermal), at a low starting dose (i.e., 1.25 mg orally once a day). This allows assessing the impact of anti-thyroid therapy on renal function. These patients should be monitored every 2 weeks. Dosage adjustments should be made prudently. The presence of overt signs of thyrotoxicosis (heart murmur, emaciation, proteinuria) underlines the importance of treating the hyperthyroidism. Management of CKD is also warranted. If the patient stabilises and renal function remains stable after reestablishment of a euthyroid state, a more definitive treatment, such as 131I, can still be considered. If renal function declines significantly after methimazole or carbimazole treatment is instituted, and more importantly if this is accompanied by a clinical deterioration of the cat, it seems wise to maintain the cat on a reversible anti-thyroid therapy, which can be adjusted individually as needed. In some cats, maintenance of a mild hyperthyroid state gives the best short term clinical result. Cats with pre-existing azotemia have a somewhat less favourable prognosis.
Development of Azotemia After Treatment of Hyperthyroidism
Resolution of the hyperthyroid state can unmask CKD. Excess thyroid hormones increase GFR and treatment of hyperthyroidism will decrease GFR, leading to an increase in BUN and creatinine values. Approximately 30% of the patients develop overt azotemia after treatment of hyperthyroidism. This underlines the importance of appropriate monitoring after therapy of hyperthyroidism. We have shown that following treatment of hyperthyroidism with 131I, renal function will be stabilized within 1 month. Therefore, we recommend evaluation of BUN and creatinine at that time point.
Predicting which initially non azotemic cats will develop overt azotemia after treatment of hyperthyroidism is currently difficult. Pre-treatment values of serum creatinine, BUN, USG and urine protein to creatinine ratio (UPC) did not appear to be predictive for the development of post-treatment renal failure in several studies. However, there are some reports of hyperthyroid cats with isostenuric urine prior to treatment who developed post-treatment azotemia. It seems reasonable to advice a trial therapy with methimazole/carbimazole for all hyperthyroid cats or at least for cats with a USG <1.030, although this remains controversial and the cut-off for USG is somewhat arbitrary. Currently the most useful predictive parameter seems to be GFR measurement. A low pre-treatment GFR was predictive of the development of azotemia in several studies. However, measurement of GFR is often impractical in a clinical setting. The usefulness of urinary markers for early renal disease is currently being investigated. Measurement of retinol binding protein (RBP), demonstrated that besides glomerular damage, these cats also have proximal tubular dysfunction. RBP did improve after treatment of hyperthyroidism and as many other clinico-pathological data, was not predictive for post-treatment azotemia.
Limited scientific evidence suggests that cats developing azotemia after treatment of hyperthyroidism have a similar prognosis like cats that remain non-azotemic. This is also our clinical impression.
Conclusion
The relationship between kidney disease and hyperthyroidism in cats is complex. It can be challenging to accurately diagnose and treat cats with concurrent CKD and hyperthyroidism. Follow-up of all cats treated for hyperthyroidism is important as a significant amount will develop CKD.
References
1. Adams WH, et al. Veterinary Radiology & Ultrasound 1997;38:231.
2. DiBartola SP, et al. Journal of American Veterinary Medical Association1996;208:875.
3. Langston CE, Reine NJ. Clin Tech in Small Anim Pract 2006;21:17.
4. van Hoek I, et al. Journal of Veterinary Internal Medicine 2009;23:1031.
5. van Hoek I, Daminet S. General and Comparative Endocrinology 2009;160: 205.
6. van Hoek I, et al. Domestic Animal Endocrinology 2009;36:45.
7. Syme HA. Vet Clin North Am-Small Anim Pract 2007;37:723.
8. Milner RJ, et al. Journal of the American Medical Veterinary Association 2006;228:559.
9. Riensche MR, et al. Journal of Feline Medicine and Surgery 2008;10:160.