Saturday, October 11, 2014

Unmasking Kidney Disease In Hyperthyroid Cats after Treatment


I have two hyperthyroid cats that both had "completely normal" kidney function until we started treating with methimazole. On treatment, the serum T4 concentrations in both cats have come down nicely to 1.2 and 2.0 µg/dl, respectively (reference interval, 1.0-4.0 µg/dl), so these values are within the low-normal range, which is what I aim for after treatment.

In the first cat, the serum creatinine has increased from 1.2 mg/dl up to 2.0 mg/dl, whereas the serum creatinine value in the second cat rose from 1.5 mg/dl up to 2.5 mg/dl. Based on the IRIS staging system, both cats could be classified as having stage 2 chronic kidney disease (CKD).

How do I manage such hyperthyroid cats that develop "new" CKD after treatment? Should I lower the methimazole or stop it all together in order to help improve the kidney function?

My Response:

Hyperthyroidism and CKD are both very common problems of the older cat and may occur concurrently in the same patient (1,2). Because hyperthyroidism increases the glomerular filtration rate (GFR) and renal blood flow (RBF), the kidney disease may be masked and only revealed once the cat is rendered euthyroid (3-5). As you know, that's what happened in these two feline patients.

However, it is very important to understand that treatment of hyperthyroidism doesn't cause new kidney problems; the CKD was already present in your cats before the methimazole treatment, but the serum creatinine values were normal, in part due to the high GFR associated with hyperthyroidism. Now that you have the hyperthyroidism under control, the lowering of circulating thyroid hormone concentrations has also resulted in a drop in GFR, unmasking the underlying CKD that was already there.

Management of hyperthyroid cats that develop kidney disease after treatment
So what do we do with hyperthyroid cats like your two patients here— cats that develop mild CKD after treatment of hyperthyroidism with methimazole?

It was once thought that if azotemia developed following medical treatment, then it would be best to stop the methimazole and leave the hyperthyroidism untreated (or at least under-treat it) to maximize renal function. This recommendation has now been widely abandoned, with the realization that hyperthyroidism could actually be causing renal injury in these cats through the process of glomerular hyperfiltration (1,2,6). This increase in glomerular pressure has been associated with proteinuria and evidence of tubular damage, which could result in progressive renal injury. In other words, hyperthyroidism has the potential to exacerbate these processes and worsen, rather than help, renal function.

On the other hand, it's also important not to over control hyperthyroidism. In other words, we don't want the post-treatment T4 concentrations to go too low because iatrogenic hypothyroidism will make the azotemia worse (7). Even mild degrees of hypothyroidism can worsen the azotemia in susceptible cats. This means that the serum T4 value does not have to be below reference range — even a serum T4 in the lower third of the reference range may be too low, especially if the serum TSH is high, diagnostic for mild hypothyroidism (8).

Because of this association between development of iatrogenic hypothyroidism and worsening of azotemia, my "goal" in treating cats with hyperthyroidism is to reduce the total T4 concentration into the middle of the reference range (e.g., 2.0-3.0 µg/dl with your lab). So in your first cat, you may want to lower the methimazole dose and allow the serum T4 to come up into the mid-normal range. This may help increase GFR and improve kidney function in that cat. One recent study found that restoration of euthyroidism in cats with iatrogenic hypothyroidism resulted in a significant reduction in serum creatinine concentration, with azotemia resolving in half of the cats (9).

Finally, if you unmask kidney disease after treatment of a hyperthyroid cat, this also means that you should take steps to attempt to slow the progression of CKD, just as you would in a geriatric cat with CKD alone. These steps may include one or more of the following, depending on secondary factors and stage of the CKD (10,11):
  • Antibiotics, if urinary tract infection
  • Antihypertensives, if hypertensive
  • Low-phosphate diet
  • Phosphorus binders
  • Calcitriol or ACE-inhibitors, if necessary
  • Subcutaneous fluids
Survival times of hyperthyroid cats that develop mild CKD after treatment
In most cats that develop newly-diagnosed azotemia after treatment for hyperthyroidism, the CKD is mild (usually IRIS stage 2) and associated with few clinical signs other than mild polyuria and polydipsia. Owners of cats that have developed azotemia still report that treatment of the hyperthyroidism has improved the clinical condition of their cat, as shown by weight gain and resolution of other clinical signs of hyperthyroidism.

The survival time of cats that develop azotemia following treatment of hyperthyroidism does not differ from those that do not develop any azotemia (7). This fact may be surprising to many practicing veterinarians who naturally assume that the development of CKD is associated with a worse prognosis. However, CKD progresses relatively slowly in cats, and only about half of all cats diagnosed with mild CKD will ultimately succumb to the disease (12). Many CKD cats die because of unrelated causes.

Survival times of hyperthyroid cats that are azotemic prior to treatment
The situation is completely different in cats that are already clearly azotemic (serum creatinine >2 mg/dl), even before any treatment for hyperthyroidism has been given. In general the survival of this group of cats with azotemic CKD prior to treatment is poor. In one study, the median survival time for azotemic cats was only 178 days; however, survival times in that study was very variable,  ranged from 0 days up to 1,505 days (4.1 years) (13).

Bottom Line:

Hyperthyroid cats that develop "new" CKD after treatment are common, but the azotemia is generally mild and we should not withhold methimazole treatment in those cats. However, we don't want to induce iatrogenic hypothyroidism, and steps should be taken to address the underlying CKD. Unless prior azotemia was present, the prognosis of most treated cats with mild CKD is good to excellent.

References:
  1. Langston CE, Reine NJ. Hyperthyroidism and the kidney. Clin Tech Small Anim Pract 2006;21:17-21.  
  2. Syme HM. Cardiovascular and renal manifestations of hyperthyroidism. Vet Clin North Am Small Anim Pract 2007;37:723-743.  
  3. Graves TK, Olivier NB, Nachreiner RF, et al. Changes in renal function associated with treatment of hyperthyroidism in cats. Am J Vet Res 1994;55:1745-1749.  
  4. Boag AK, Neiger R, Slater L, et al. Changes in the glomerular filtration rate of 27 cats with hyperthyroidism after treatment with radioactive iodine. Vet Rec 2007;161:711-715.  
  5. van Hoek I, Lefebvre HP, Peremans K, et al. Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine. Domest Anim Endocrinol 2009;36:45-56.  
  6. Syme H. Are methimazole trials really necessary? In: Little SE, ed. August's Consultations in Feline Internal Medicine: Elsevier, 2014;in press.
  7. Williams TL, Elliott J, Syme HM. Association of iatrogenic hypothyroidism with azotemia and reduced survival time in cats treated for hyperthyroidism. J Vet Intern Med 2010;24:1086-1092.  
  8. Peterson ME. Feline focus: Diagnostic testing for feline thyroid disease: hypothyroidism. Compendium 2013;35:E4. 
  9. Williams TL, Elliott J, Syme HM. Effect on renal function of restoration of euthyroidism in hyperthyroid cats with iatrogenic hypothyroidism. J Vet Intern Med 2014;28:1251-1255. 
  10. Bartges JW. Chronic kidney disease in dogs and cats. Vet Clin North Am Small Anim Pract 2012;42:669-692.
  11. Polzin DJ. Chronic kidney disease in small animals. Vet Clin North Am Small Anim Pract 2011;41:15-30. 
  12. Elliott J, Rawlings JM, Markwell PJ, et al. Survival of cats with naturally occurring chronic renal failure: effect of dietary management. J Small Anim Pract 2000;41:235-242.
  13. Williams TL, Peak KJ, Brodbelt D, et al. Survival and the development of azotemia after treatment of hyperthyroid cats. J Vet Intern Med 2010;24:863-869. 

4 comments:

Luke Wagner said...

Dr. Peterson- As of this am,. Our beloved 10 year old family cat , Ruth, is hyperthyroid. Her T4 level is 9.58. Considering I131 rx,but concern is she also has renal and ureter uroliths. We have been monitoring her renal values and have remained normal for the last ~ 2 years .She is acting well however has dropped ~2 lbs in last 3 weeks or so. Would appreciate your thoughts on how you would approach treatment in this situation. Nearest treatment facility has opening Nov 17, but have reservations about how to proceed..In the interim ,I was going to start her out on low dose 1.25mg transdermal gel BID . Much appreciated, Luke Wagner ,DVM

Dr. Mark E. Peterson said...

I'd give the methimazole for at least a month and then monitor T4 and renal values. You want to drop the T4 down to the mid-normal range to evaluate renal function. If the azotemia becomes much worse, you might not want to treat with I-131 until you have resolve the uroliths, etc.

badhair said...

Dr Peterson,

My cat underwent I-131 and now has renal failure as indicated by a creatanine of 2.5, high normal is 2.4. She was put on a medication trial prior to I-131 and her T4 was 2.2 and her creatanine 1.6. I think the I-131 causes kidney issues , it can't mask what wasn't there . I regret doing this to her . She had 2mCi administered after reaching a T4=6. It was caught when she was only T4=4 and i was advised to wait . It seems there is some damage done by I-131 and now I've destroyed her kidneys . Her T4 was 1.8 at 6 weeks post tx and her creatanine 2.5! At 3.5 months post tx her T4=2.3 and her creatanine still 2.5. Her phosphorus is 3.3 (2.4-8.2) and her BUN 25 (14-36). What is her prognosis and what can I do aside from the prescription diet? How long can she live? Have I given her a death sentence for sending her for I-131 tx? Please advise , thank you for your time .

Dr. Mark E. Peterson said...

First of all, methimazole trials are far from perfect, and I have stopped doing them becuase they cannot always predict which cats have CKD.

Did you read this blog post? Your cat's prognosis is reasonably good and survival time could be years. As the post says, rule out hypertension and urinary tract infection. A low phosphate diet is the best (or use phosphate binders).

Also do a TSH level to make sure that your cat isn't mildly hypothyroid. In those cases, treated with thyroid hormone could reverse the high kidney levels.