Feline hyperthyroidism and chronic renal failure (CRF) are common diseases in older cats. Further, renal function is profoundly influenced by thyroid status in several species. 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.

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 (CO). Further, hyperthyroidism diminishes peripheral vascular resistance by dilating arterioles of the peripheral circulation. This leads to a stimulation of the renin-angiotensin-aldosterone system, which contributes to the increased CO. As a consequence of these processes, an increased RBF is observed. Opposite changes are described in hypothyroid humans and rats.

The increased GFR associated with hyperthyroid states is thought to result from the increased CO and intrarenal vasodilatation and leads to a decline in BUN and serum creatinine concentrations. Opposite changes are observed in hypothyroidism (human) and studies have shown a normalisation of GFR, BUN and creatinine values after successful treatment of hypo- or hyperthyroidism in human medicine.

Considerations and Clinical Implications in Hyperthyroid Cats

It is important to underline that CRF 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. Further as shown in table 1, renal function will decline after treatment of hyperthyroidism in cats. This can unmask renal failure 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 CRF. 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 CRF at presentation. Another study on a larger number of cases (n=167) reported that 14% of hyperthyroid cats had pre-existing renal disease (Milner et al., 2006). Approximately 30% of hyperthyroid cats are azotemic after therapy of hyperthyroidism.

Assessment of complete blood count, chemistry, urinalysis and blood pressure are important in hyperthyroid cats prior to treatment. Indeed, careful evaluation of BUN, creatinine and urine specific gravity (USG) are required prior to instituting therapy for hyperthyroidism as these results will influence the initial choice of therapy for hyperthyroidism. 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.

Pre-existing renal failure in a newly diagnosed hyperthyroid cat: First, in such a case, the diagnosis of mild 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 wise to start an azotemic hyperthyroid cat with a reversible anti-thyroid therapy (trial therapy). Often, methimazole is 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 CRF 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 treatment is instituted, 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 may be beneficial.

Development of renal failure after treatment of hyperthyroidism: Resolution of the hyperthyroid state can unmask renal failure. Excess thyroid hormones increase GFR and treatment of hyperthyroidism will decrease glomerular filtration, leading to an increase in BUN and creatinine values. Approximately 30% of the patients develop overt CRF after treatment of hyperthyroidism. This underlines the importance of appropriate monitoring after therapy of hyperthyroidism.

Predicting which non azotemic cats will develop renal failure 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 (although not evidence-based) to recommend a trial therapy in any hyperthyroid cat presented with one or more of the following: BUN or serum creatinine values at the high end of the reference interval, a low USG, an increased UPC or marked ultrasonographic kidney abnormalities. Currently the most useful predictive parameter seems to be GFR measurement. A low pre-treatment GFR was predictive of the development of CRF in several studies. However, measurement of GFR is often impractical in a clinical setting. Usefulness of urinary markers of early renal disease is currently being investigated.

Keeping in mind the negative effects on renal function, described in rats and humans in hypothyroid states, it seems important to avoid a hypothyroid state after treatment of hyperthyroidism in cats.

The relationship between kidney disease and hyperthyroidism in cats is complex. It can be challenging to accurately diagnose and treat cats with concurrent CRF and hyperthyroidism. Follow-up of all cats treated for hyperthyroidism is important as a significant amount will develop CRF.

Table 1. Follow-up of renal function after treatment of hyperthyroidism in cats.

Hyperthyroid: HT, Methimazole: MMI, thyroidectomy: SX, Radioactive iodine: 131I. Mean values for USG, GFR and creatinine are given prior to and after therapy of hyperthyroidism.

References

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