TANYA'S

COMPREHENSIVE GUIDE TO

FELINE CHRONIC KIDNEY DISEASE

 

 

 

 

PROTEINURIA

 

ON THIS PAGE:


What is Proteinuria?


Why Proteinuria is Important


Other Causes


Symptoms


Diagnosis


Treatments, Including Benazepril (Fortekor) and Telmisartan (Semintra)


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Home > Key Issues > Proteinuria

 


Overview


  • Proteinuria (excess protein in the urine) is important because it may make CKD progress faster.

  • It is also used to determine the stage of CKD.

  • This page explains more about proteinuria and how you can deal with it.


What is Proteinuria?


 

Healthy cats only have tiny amounts of protein in their urine because their kidneys do not allow the protein to leak through. If this mechanism is not working properly for some reason, there will be excess levels of protein in the urine. This is called proteinuria.

 

The main proteins which leak through are albumin and globulin, so it is also sometimes referred to as microalbuminuria.

 

The International Renal Interest Society (2013) states that proteinuria may be renal or post-renal:

  • Renal: the proteinuria is caused by the kidneys not working properly.

  • Post-renal (or non-renal): the proteinuria is caused by a part of the urinary tract other than the kidneys depositing protein in the urine. This is commonly caused by urinary tract infections, inflammation or blood loss.


Why Proteinuria is Important


 

Proteinuria is important because it may make CKD progress faster. In Chronic kidney disease (CKD) in dogs and cats - staging and management strategies (2015) A Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference, Dr D Chew states "Protein in urine is both a marker and a creator of more renal disease." He has a helpful diagram on page 10 showing how proteinuria happens.

 

It is not known exactly why proteinuria worsens kidney disease in cats. Feline chronic kidney disease and the proteinuric conundrum (2014) Sparkes A Presentation to the Australian and New Zealand College of Veterinary Scientists Science Week 2014 states "It is thought, in humans at least, that proteins in the tubular fluid (passing through a damaged glomerulus) provoke an inflammatory response that produces further renal damage", and it is possible that the same thing occurs in cats.

 

In Proteinuria - what is this and why do we worry about it? (2014) Dr S Caney p34 states that proteinuria may damage kidney function in cats in three different ways, by:

  • "overwhelming the ability of the proximal tubule cells to resorb protein from the glomerular filtrate"

  • "protein leaking into the interstitial space and triggering inflammatory cascades"

  • "blocking tubules leading to their loss"

Whatever the precise mechanism, clearly it is important to know about and treat proteinuria.

 

Proteinuria also plays an important role in the early detection of CKD, and is used to help diagnose and stage CKD.

 


Other Causes


 

Other causes of proteinuria include diabetes and hypertension. In Management of chronic renal failure: beyond the can, a presentation to the Atlantic Coast Veterinary Conference 2001 (scroll to No. 3), Dr MS Wallace mentions that hypertension may promote proteinuria.

 

Blood in the urine, infection or inflammation may give a false positive result, causing post-renal proteinuria.

 


Symptoms


 

One commonly seen symptom of proteinuria is foamy urine. Proteinuria may also cause weight loss, and swelling in the legs, abdomen or face

 

The National Kidney and Urologic Diseases Information Clearing House is a human site with information about the symptoms of proteinuria.

 


Diagnosis


 

Proteinuria is diagnosed via a urine sample. See the Diagnosis chapter for more information on obtaining urine samples.

 

The International Renal Interest Society (2013) states that the most commonly used method of obtaining urine to check for proteinuria is via the urine dipstick test but that it is not always very accurate and may give false positive or false negative results. Urine protein-to-creatinine concentration ratio in samples collected by means of cystocentesis versus manual compression in cats (2015) Vilhena HC, Santos RR, Sargo TJ, Lima TB, Dias SS, Pastorinho MR, Queiroga FL & Silvestre-Ferreira AC Journal of the American Veterinary Medicine Association 246(8) pp862-867 discusses whether the urine collection method affects the accuracy of the result, and also found the urine dipstick test was not particularly accurate, but mentions that cystocentesis may cause blood in the urine, which in some cases may adversely affect the result.

 

Infection or inflammation may also give a false positive result.

 

It is recommended that three urine samples should be collected over a minimum period of two weeks before a conclusion is drawn.

 

The degree of proteinuria is usually indicated by the number of + signs on the test result, with more + indicating greater severity, so Protein +++ is more severe than Protein +.

 

Cornell University College of Veterinary Medicine explains more about the diagnosis of proteinuria.

 

Proteinuria Staging and Prognosis: Urine Protein:Creatinine Ratio (UPC Ratio)


The International Renal Interest Society (2015) uses proteinuria as a risk factor for the development of CKD, and as one factor in determining the severity of the CKD. It does this by measuring the UPC ratio, which is the ratio of protein (in the urine) to the cat's creatinine level (in the blood). Idexx Laboratories offers a test in a number of different countries which can calculate the protein:creatinine ratio. It is part of their catalyst 1 test.

 

IRIS grades the UPC ratio as follows:

 

Urine Protein: Creatinine Ratio

Proteinuria Status

Below 0.2

Non Proteinuric (NP)

Between 0.2 and 0.4

Borderline Proteinuric (BP)*

Over 0.4

Proteinuric (P)

*Check again within two months

 

There is a correlation between the severity of proteinuria and the prognosis. Survival of cats with naturally occurring chronic renal failure is related to severity of proteinuria (2006) Syme HM, Markwell PJ, Pfeiffer D & Elliott J Journal of Veterinary Internal Medicine 20 pp528–535 found that cats with a urine protein:creatinine ratio below 0.5 survived almost three times as long as cats with a urine protein:creatinine ratio of over 0.5.

 

However, don't panic if your cat's level is over 0.4 because the UPC ratio is not always accurate - for example, blood in the urine, infection or inflammation may give a false positive result. Hypertension may worsen proteinuria, so getting blood pressure under control may lead to an improvement in the UPC ratio. The UPC ratio is often higher if the cat has glomerulonephritis.

 

Even if your cat's UPC ratio is indeed high, it may gradually reduce with treatment.

 

Cornell University College of Veterinary Medicine has some information about the UPC ratio.

 


Treatments


 

Laboratory evaluation in dogs and cats with chronic kidney disease (2015) Grauer GF Clinician's Brief May 2015 pp65-69 states that there is "increasing evidence that anti-proteinuric treatments can slow the progressive nature of CKD." He goes on to say "Tighter control of hyperphosphatemia, renal proteinuria, and systolic hypertension may improve treatment outcome."

 

Diet


Feeding a reduced protein but high quality protein food may be of some use. Nutritional management of feline chronic kidney disease (2008) Elliott J, Elliott D Veterinary Focus 18(2) pp39-44 states that "protein restriction may "decrease proteinuria mediated by glomerular hyperfiltration, a mal-adaptive response to CKD which contributes to progressive renal injury. This is the reason for reducing protein intake in Stages 2 and 3 of CKD." However, the authors themselves admit that "The efficacy of reducing protein intake as a treatment for proteinuria is highly controversial in the cat and dog", adding that this may lead to malnutrition.

 

Omega 3 essential fatty acid supplements are of benefit to humans with proteinuria but it is not known if they have the same effect for cats. Proteinuria in dogs and cats (2012) Harley L & Langston C Canadian Veterinary Journal 53(6) pp631–638 states "High dose omega 3 polyunsaturated fatty acids (n3 PUFAs) in the form of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to reduce proteinuria in humans with glomerular disease. It is also possible that renal eicosanoid production may be affected, reducing inflammation and vasoconstriction; the n3 PUFAs are renoprotective in the dog. Dogs consuming n3 PUFAs have lower mortality, increased renal function, and reduced proteinuria and cholesterol (2,32,41). The dose of n3 PUFAs is not known in dogs and cats and dosing is extrapolated from human data. Prescription renal diets, however, are often supplemented with n3 PUFAs."

There is as yet no evidence that these treatments will reduce proteinuria, but they are usually worth trying for a CKD cat for other reasons (see Nutritional Requirements), so I would speak to your vet about trying them.

Stem Cell Transplants


Studies indicate that stem cell transplants may improve proteinuria in rats with induced kidney injury. There is as yet no evidence that they may do the same for cats.

Medications


The main medications are:


ACE Inhibitors (ACEI) and Angiotensin II Receptor Blockers (ARBs)


 


ACE Inhibitors


What are ACE Inhibitors?


ACE inhibitors are heart medications. They work by preventing the conversion of a hormone called angiotensin I into another hormone called angiotensin II, the role of which is to constrict blood vessels. The ACE inhibitor thus relaxes the blood vessels, which helps to reduce blood pressure and therefore reduces the work that the heart has to perform to pump blood through the body.

 

Because of this, ACE inhibitors are sometimes used to control hypertension (high blood pressure), and their use for this purpose is covered on the Hypertension page. The main reason they tend to be used for CKD cats, however, is for reducing proteinuria.

 

Benazepril (Fortekor, Benazecare, Lotensin)


One ACE inhibitor, benazepril, is approved for the treatment of CKD in cats in Europe, Australasia and Canada. If you are in these countries, it is therefore highly likely that your vet will offer you this treatment at some stage. Indeed, in the UK, benazepril and therapeutic kidney diets are often the only treatments offered (though if they were all that is available or suitable for CKD cats, this site would be a lot shorter than it is!).

 

Benazepril is sold under the trade names of Fortekor or Benazecare in Europe and Canada and under the trade name of Lotensin in the USA. 

 

Since in practice most people who are offered an ACE inhibitor will be offered benazepril, much of what is stated below focuses on this medication, particularly since almost all the research into the use of ACE inhibitors in cats relates to benazepril. 

 

Pet Place has some information about benazepril.

 

Enalapril (Enacard)


Another member of the ACE inhibitor family is enalapril (Enacard). This is excreted largely by the kidneys, so is not usually the best choice for a CKD cat. Benazepril is primarily excreted (85%) via the liver in cats, which puts less strain on the kidneys.

 

Mar Vista Vet has more information on enalapril.

Using ACE Inhibitors to Control Proteinuria


ACE inhibitors may improve proteinuria because they block the negative effects of angiotensin II (see above). This can lead to a reduction in the amount of blood flowing through the kidneys, which in turn may reduce the glomerular filtration rate, a measure of kidney function. Chronic kidney disease (CKD) in dogs and cats - staging and management strategies (2015) Chew D A Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference explains more about this on pages 10 and 11 (it is quite technical).

Proteinuria in cats with chronic kidney disease (2008) is a video presentation by Dr CL Langston of the Animal Medical Center in NYC. Dr Langston starts benazapril if  the UPC ratio is over 0.4.

 

Evaluation of the clinical efficacy of benazepril in the treatment of chronic renal insufficiency in cats (2006) Mizutani H, Koyama H, Watanabe T, Kitagawa H, Nakano M, Kajiwara K & King JN Journal of Veterinary Internal Medicine 20(5) pp1074-9 tested benazepril on 61 cats with naturally occurring CKD in a randomised double-blind placebo-controlled study. The study found that UPC ratios were significantly lower with benazepril when compared with the placebo at days 120 and 180. "Incidence rates of cats with IRIS classification stage 2 or stage 3 that remained in stage 2 or 3 without progressing to stage 4 were higher with benazepril (93 +/- 5%) as compared with placebo (73 +/- 13%)."

 

Although ACE inhibitors do reduce proteinuria in cats, it is not clear whether this makes a real difference in lifespan. Tolerability and efficacy of benazepril in cats with chronic renal disease (2006) King JN, Gunn-Moore DA, Tasker S, Gleadhill A & Strehlau G Journal of Veterinary Internal Medicine 20(5) pp1054-1064 found that benazepril improved proteinuria in cats in the study, and cats with more severe proteinurua (a UPC ratio greater than 1.0) who received benazepril showed improved appetite and weight gain, and had an average survival time of 402 days versus 126 days for those cats being treated with a therapeutic kidney diet only. However, the study states "there was no difference in renal survival time between the two groups when all 192 cats were compared."

 

Therapeutic implications of recent findings in feline renal insufficiency (2009) Scherk M Presentation to the International Congress of the Italian Association of Companion Animal Veterinarians states "Benazepril has undergone a large, multiinstitutional study to assess its effects on CRI in cats. Results of this and other smaller studies show that using benazepril or placebo didn’t make any significant difference in survival time for all CRI cats. For cats with urinary protein loss (urine protein:creatinine, UPC), benazepril treated cats had longer survival times and better appetite than placebo-treated urinary protein losing cats."

 

Benazepril (Fortekor) Dosing


Benazepril comes in tablet form in either 2.5 mg or 5 mg sizes.

 

When given to treat proteinuria, the usual dose is 0.5 - 1.00 mg per kg of body weight once each day, so a 10 lb (4.5 kg) cat would receive 2.25mg a day. In practice, the manufacturer recommends that it be administered as follows:

 

Cat Weight Number of 2.5mg tablets
2.5 - 5.0 kg or 5.5 - 11 lbs 1 tablet
  5.0 - 10.0 kg or 11 - 22 lbs    2 tablets

In light of the cautions immediately below, it may be safer to start with half the dose, only increasing gradually.

 

ACE Inhibitor Cautions, Interactions and Side Effects


Fortekor has not been tested in cats weighing less than 2.5kg (5 lbs) so be careful if you have a small cat. 

 

Increased Creatinine Levels


In some cats, creatinine levels may rise shortly after beginning benazepril. Therefore the manufacturer of Fortekor recommends that kidney bloodwork should be checked 5-10 days after starting the medication, though very few vets seem to do this routinely. For most cats this increase will be temporary, but monitor your cat to be sure. If your vet does not think this is necessary, show him or her some of the following links.

 

Blood pressure in small animals Part 2: hypertension target organ damage heart and kidney (2009) Carr AP & Egner BE European Journal of Companion Animal Practice 19(1) pp1-5 states "When using ACEi, it is important to monitor for azotemia as this can occur secondary to the vasodilator effect."

 

In Chronic kidney disease (CKD) in dogs and cats - staging and management strategies (2015) A Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference, Dr D Chew states "General guidelines for use of ACE-inhibitors in CKD include rechecking renal function in 1 week following start of ACE-inhibition to make sure that GFR has not been reduced too much. It is common to see a small increase in serum creatinine at this time (20 to 30% increase over baseline). If creatinine has increased too much, reduce the dose of the ACE-inhibitor. Some dogs and cats are ACE-inhibitor intolerant in that their renal function will be much worse during initial treatments so that treatment must be discontinued. We also recommend to recheck the UPC 1 and 3 months after the start of ACE-inhibition. The goal is to achieve a 50% decrease in UPC in those in which it was initially increased." 

Therapeutic implications of recent findings in feline renal insufficiency (2009) Scherk M Presentation to the International Congress of the Italian Association of Companion Animal Veterinarians states "Cats with an increased UPC (> 0.4) who are started on this medication, should be rechecked within 3-7 days and have their renal parameters, hydration, body weight, appetite and overall health monitored. Thereafter, re-evaluation should occur every 2-4 months in a stable patient. If there is no decrease in UPC, the medication should be discontinued."

 

ACE Inhibitors and Dehydrated Cats


It is very important not to use ACE inhibitors in dehydrated cats because doing so can push them over the edge. ACVIM Consensus Statement: guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats (2007) Brown S, Atkins C, Bagley R, Carr A, Cowgill L, Davidson M, Egner B, Elliott J, Henik R, Labato M, Littman M, Polzin D, Ross L, Snyder P, and Stepien R Journal of Veterinary Internal Medicine 21 pp542–558 says "ACEI should not be used in dehydrated patients in which the GFR might drop precipitously. These patients should be carefully rehydrated and then re-evaluated before instituting antihypertensive therapy."

 

The International Renal Interest Society (2015) warns "Take care not to introduce CCB/ACEI treatment to unstable dehydrated cats where GFR [a measure of kidney function] may drop precipitously if CCB/ACEI are introduced before the patient is adequately hydrated."

 

Proteinuria (2013) Presentation to the 38th World Small Animal Veterinary Association World Congress, Dr H Syme states "Treating cats that are severely azotaemic or that have prerenal azotaemia with ACE-inhibitors may actually speed their demise."

 

Despite this, I often hear of British cats who have high kidney values being sent home with benazepril after a session on intravenous fluids, but with no access to sub-Qs. Please be careful if this applies to you, because your cat will probably become dehydrated without sub-Qs.

 

Effects on Potassium Levels and Anaemia


The use of ACE inhibitors may also lead to an increase in potassium levels in the blood, which could be a risk in a cat who already has high levels of potassiumDrugs discusses this. However, Tolerability and efficacy of benazepril in cats with chronic renal disease (2006) King JN, Gunn-Moore DA, Tasker S, Gleadhill A & Strehlau G Journal of Veterinary Internal Medicine 20(5) pp1054-1064 found that "benazepril had no relevant effect on plasma potassium concentrations and in particular did not contribute to hyperkalemia."

 

There is some debate as to whether ACE inhibitors may exacerbate anaemia and/or induce some resistance to the use of erythropoiesis stimulating agents (Aranesp, Epogen, Procrit or Eprex) in humans. The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin (1999) MacDougall IC Nephrology Dialysis Transplantation 14(8) pp1836-1841 reports on the evidence for and against this concern in humans.

 

Interactions and Side Effects


Using ACE inhibitors at the same time as diuretics such as furosemide (Lasix), whilst sometimes necessary in cats with heart disease, can be dangerous. Mar Vista Vet has more information about this.

Non-steroidal anti-inflammatories (NSAIDs), including meloxicam (Metacam), may increase the effects of benazepril and reduce blood pressure too far, so do not give both medications to your cat  without checking with your vet first. 

 

ACE inhibitors should be given two hours apart from phosphorus binders, because the binders may reduce the bioavailability of the ACE inhibitors. Drugs has more information about this.

 

ACE inhibitors may cause lethargy, particularly when first begun. This may be a sign that blood pressure has fallen too low, which in turn may lead to an increase in creatinine levels as described above. Coughing may also be seen. Some cats exhibit vomiting and/or reduced appetite. Diarrhoea may also occur.

 

Pet Place discusses benazepril, including possible side effects.

 

Whether to Use ACE Inhibitors


The potential downsides of using ACE inhibitors (a decreased GFR and increased creatinine levels) are usually considered to be an acceptable price to pay for the benefits (reduced intraglomerular pressure) in humans. This trade off appears to also be accepted for cats in Europe, Australasia and Canada, where benazepril in particular is routinely prescribed for CKD cats. In the USA, ACE inhibitors are not used routinely, and are usually only prescribed if a cat has significant proteinuria, or if amlodipine alone is not sufficient to control hypertension.

 

Although studies indicate that ACE inhibitors may reduce proteinuria, they have not indicated an increase in survival time. Feline chronic kidney disease and the proteinuric conundrum (2014) Sparkes A Presentation to the Australian and New Zealand College of Veterinary Scientists Science Week 2014 says "interventional treatment with ACEIs, while reducing the degree of proteinuria has not yet been shown to have a survival benefit."

 

Prolonging life and kidney function (2009) Chew DJ & DiBartola SP Proceedings of the Southern European Veterinary Conference & Congreso Nacional states "Angiotensin-converting enzyme (ACE) inhibitors (e.g. enalapril, benazepril) may have protective effects in patients with chronic renal disease due to their ability to block adverse effects of angiotensin II. ACE-inhibition reduces glomerular capillary hydraulic pressure by decreasing postglomerular arteriolar resistance. Proteinuria is decreased secondary to decreased glomerular hydraulic forces and development of glomerulosclerosis is limited when protein trafficking across the glomerulus is decreased. Remnant nephrons in animals with CRF have glomerular hypertension that can benefit from reductions in transglomerular forces. An additional potential benefit from ACE-inhibition is improved control of systemic blood pressure. This beneficial effect must be balanced against their potential to worsen azotemia since glomerular pressure provides the driving force for GFR in the “super-nephron”.

 

Chronic kidney disease in dogs and cats II: Principles of management (2010) Maddison J & Syme H Irish Veterinary Journal 63(2) pp106-9 states "There is evidence that use of ACE inhibitors (such as benazapril) will attenuate the progression of renal failure in humans and animals with significant proteinuria. However, the evidence that they are beneficial in patients with mild proteinuria (the majority of cats) has not yet been clearly established. There is a rationale for using ACE inhibitors in cats and dogs with renal failure as there may be some benefit provided the patient can be pilled easily and the owner can afford the treatment. However, dietary change (reduction in phosphate) carries significantly greater potential benefits in slowing the progression of non-proteinuric renal failure and ACE inhibitor therapy should not be regarded as a substitute for it. Treating cats and dogs that are severely azotaemic, or that have pre-renal azotaemia with ACE-inhibitors may actually speed their demise."

 

The effects of Rheum officinale on the progression of feline chronic kidney disease (2011) Hanzlicek AS Thesis submitted to Kansas State University College of Veterinary Medicine states "Based on easily measured clinical parameters, this study failed to detect a significant difference in cats administered a Chinese rhubarb supplement, benazepril, or both."

 

Some members of Tanya's CKD Support Group have found benazepril helpful whilst others felt it did not suit their cat and in some cases caused problems. Personally, I would be prepared to use benazepril if I had a cat with proteinuria. I would also be prepared to use it if my cat had hypertension uncontrolled by amlodipine alone. I don't think I would use it in a cat without these problems, particularly not in a cat with creatinine over 3.5 mg/dl (USA) or 310 µmol/L (international). This level is arbitrary, and simply reflects my own feelings of what might be a reasonable cut-off point.

 

If your vet offers you benazepril, please discuss it fully with him/her and try to decide together whether you think it could benefit your cat with his/her particular symptoms, bloodwork and quality of life. If you do decide to use it, please check Side Effects and Interactions above, particularly the part about dehydrated cats. Whatever your cat's numbers, you should have bloodwork run 5-10 days after beginning to use benazepril, and monitor blood pressure (see above).

 

If you are already using benazepril and you have any concerns, please also talk to your vet but do not stop it suddenly. As a heart medication, it should be gradually tapered down.


Angiotensin II Receptor Blockers (ARBs)


What are Angiotensin II Receptor Blockers (ARBs)?


Angiotensin II receptor blockers (ARBs) are heart medications but they work in a slightly different way to ACE inhibitors. Angiotensin II is a hormone, the role of which is to constrict blood vessels. This type of medication works by blocking the receptor to which angiotensin II attaches, thus relaxing the blood vessels, which in turn helps to reduce blood pressure and therefore reduces the work that the heart has to perform to pump blood through the body. These medications are sometimes referred to as angiotensin II receptor antagonists.

 

In human medicine ARBs tend to be used when ACE inhibitors cannot be used for some reason.

 

Telmisartan (Semintra)


Telmisartan is an ARB. Its trade names include Micardis in the USA and Semintra in Europe. I first heard about the use of telmisartan in cats because an American vet school was investigating the use of telmisartan to control blood pressure.

 

Telmisartan was launched in Europe in September 2013 and in Canada in June 2014 under the name of Semintra as a treatment for proteinuria in cats. A patent application was filed in the USA in 2013. In the meantime, generic telmisartan is available in the USA.

 

Boehringer Ingelheim has a leaflet about how Semintra works.

 

Drugs has some information about the use of this drug in humans, as does Patient UK.

Using Angiotensin II Receptor Blockers to Control Proteinuria


In December 2012 Boehringer Ingelheim were given approval in Europe for the use of telmisartan for the "reduction of proteinuria associated with chronic kidney disease (CKD) in cats” under the trade name of Semintra. The European Medicines Agency has some information about the approval of Semintra, and mentions that in one field trial of around six months duration involving 224 cats, Comparison of efficacy of long-term treatment with telmisartan and benazepril in cats with chronic kidney disease (2015) Sent U, Gössl R, Elliott J, Syme HM, Zimmering T Journal of Veterinary Internal Medicine 29(6) pp1479-87, telmisartan was found to be as effective as benazepril in reducing proteinuria and may in the future be shown to be more effective at controlling proteinuria.

Telmisartan (Semintra) Dosing


According to the European Medicines Agency EPAR Summary for the Public, the usual dose when treating for proteinuria is 1 mg per kg (2.2. lbs) body weight each day.

 

Semintra comes in liquid form in a 30ml bottle, with a 4mg/ml strength, i.e. each ml contains 4 mg of telmisartan. Therefore you would give 0.25ml per kg of body weight each day, so a 10 lb (4.5 kg) cat would receive 1.125ml a day. This means the bottle would last for almost four weeks.

 

In light of the cautions immediately below, it may be safer to start with half the dose, only increasing gradually.

Telmisartan can be given orally or mixed with food. It takes effect within seven days.

 

The UK National Office for Animal Health has some information on Semintra.

 

Angiotensin II Receptor Blockers Cautions, Interactions and Side Effects


The advice for ARBs is very similar to that for ACE inhibitors:

 

Increased Creatinine Levels


As yet there is little information about the effects of telmisartan in cats, but RX List states "a 0.5 mg/dL rise or greater in creatinine was observed in 0.4% telmisartan patients compared with 0.3% placebo patients." The same thing is quite possible in cats so caution should be exercised, as with benazepril.

Effects on Potassium Levels and Anaemia


Drugs states "Hematologic side effects have included anemia."

 

CVMP assessment report for Semintra (EMEA/V/C/002436) (2012) discusses the approval of telmisartan for proteinuric cats in Europe and states "Other effects were: reversible increases in serum potassium; reversible increases in urea nitrogen and creatinine; reversible decreases in red blood cell parameters; and slightly elevated values for AST, ALT and bilirubin." These increases were actually seen in dogs and rats, but it adds "Given the possibility for effects on red blood cell parameters, the SPC includes a recommendation that red cell count should be monitored during therapy."

 

Interactions and Side Effects


The European Medicines Agency EPAR Summary for the Public states that vomiting or diarrhoea may occasionally be seen.

 

RX List says of meloxicam (Metacam), a non-steroidal anti-inflammatory (NSAID) and telmisartan "Either increases toxicity of the other...May result in renal function deterioration, particularly in elderly or volume depleted individuals", so do not give both medications to your cat  without checking with your vet first. 

 

Whether to Use Angiotensin II Receptor Blockers


Telmisartan has been available as Semintra in Europe for over three years now, and like benazepril (Fortekor), some members of Tanya's CKD Support Group think it is helpful whilst others felt it did not have any benefits.

 

As with benazepril, I would be prepared to use telmisartan if I had a cat with proteinuria, but until more research into ARBs in cats has been performed, I don't think I would bother otherwise.

 


ACE Inhibitors or Angiotensin II Receptor Blockers


I am sometimes asked whether it is better to use benazepril or telmisartan. There is a lot more research into the use of benazepril in cats than there is into telmisartan. According to CVMP assessment report for Semintra (EMEA/V/C/002436) (2012), even the study on which the approval of Semintra was based did not focus on its effectiveness as such, but rather "was designed to show that telmisartan is as efficacious as the comparator, the ACE inhibitor benazepril, to reduce proteinuria in CKD in the cat." 

 

In Chronic kidney disease (CKD) in dogs and cats - staging and management strategies (2015) A Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference, Dr D Chew states that "It is not clear when or if an ARB should be chosen to reduce RAAS activity instead of an ACE-Inhibitor for treatment of CKD in veterinary patients to reduce proteinuria, systemic blood pressure, or intrarenal inflammation."

 

Feline CKD: New horizons - where do we go from here? (2013) Taylor S & Sparkes AH Journal of Feline Medicine & Surgery 15 Suppl 1 pp45-52 states "Despite some potential advantages of the use of ARBs in human CKD, their efficacy appears to be similar to that of ACE inhibitors, effected via a reduction in glomerular capillary pressure and improvement in permselectivity of the glomerular capillary barrier, and hence a reduction in proteinuria and arrest of progression in proteinuric renal diseases. The use of ACE inhibitors and ARBs in human CKD thus appears largely to be interchangeable, with NICE guidelines in the UK not indicating a preferred treatment." It adds that further research is necessary to fully assess how useful telmisartan can be in cats.

 

However, Attenuation of the pressor response to exogenous angiotensin receptor blockers and benazepril hydrochloride in clinically normal cats (2015) Jenkins, TL, Coleman AE,e Schmiedt CW & Brown SA American Journal of Veterinary Research 76(9) pp807-13 compared the effectiveness of three ARBs, including telmisartan, and benazepril. It concluded that "Results indicated that telmisartan administration may have advantages over benazepril administration for cats with renal or cardiovascular disease." It should be noted that the medications were tested in only six healthy, young cats.

 


Combining ACE Inhibitors and Angiotensin II Receptor Blockers


In humans, ACE inhibitors and ARBs are occasionally used together, usually when the patient is on the maximum dose of an ACE inhibitor but is still having problems such as proteinuria not being fully controlled. However, Health Canada states (with regard to humans) "Recent studies have demonstrated that any combination of aliskiren, ACEIs or ARBs increases the risks of hypotension (low blood pressure), hyperkalemia (high levels of potassium in the blood) and kidney problems."

 

Feline CKD: New horizons - where do we go from here? (2013) Taylor S & Sparkes AH Journal of Feline Medicine & Surgery 15 Suppl 1 pp45-52 states "Studies will also be needed to see if combined ACE inhibitor and ARB therapy may have additional benefits in cats with CKD for control of blood pressure, control of proteinuria and improved survival, as is seen in some humans with CKD. An increase in adverse renal outcomes in some studies, however, means indications for dual RAAS blockade remain controversial."

 

Dual blockade of the renin-angiotensin system with angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) (2011) Ritter JM British Journal of Clinical Pharmacology 71(3) pp313–315 says that while a "trial of the combination of telmisartan (ARB) with ramipril (ACE inhibitor) versus monotherapy showed that combined therapy achieved a mean blood pressure reduction 2.4/1.4 mm Hg greater in the combination group than in the group treated with ramipril alone and a greater effect on urinary albumin excretion, the combination showed no benefits in terms of the primary study endpoint (a composite of cardiovascular death, myocardial infarction, stroke and hospitalisation for heart failure), caused more symptoms attributable to hypotension, and increased the decline in renal function and need for dialysis compared with ACE inhibitor monotherapy...Thus clinical endpoint evidence does not support combined use of ACE inhibitor with ARB... Messerli concluded that ‘unless data emerge to the contrary, dual blockade should no longer be used in clinical practice’."

 


Links


 

Chronic kidney disease (2007) Polzin D Delaware Valley Academy of Veterinary Medicine has some information about proteinuria (page 17).

Proteinuria in dogs and cats (2012) Harley L & Langston C Canadian Veterinary Journal 53(6) pp631–638 has a good overview.

The International Renal Interest Society (2013 has an article about proteinuria by Dr GF Grauer.

Proteinuria and renal disease: a round table discussion (2005) is an interesting discussion by a number of veterinary specialists about proteinuria, and CKD generally.

Assessment and management of proteinuria in dogs and cats: 2004 ACVIM Consensus Statement (Small Animal) (2005) Lees GE, Brown SA, Elliott J, Grauer GF & Vaden SL Journal of Veterinary Internal Medicine 19 pp377-385 gives suggestions for the diagnosis and treatment of proteinuria.

Proteinuria in cats with chronic kidney disease (2008) is a video presentation by Dr CL Langston of the Animal Medical Center in NYC.

When does protein in a urine sample necessitate further patient evaluation and treatment (2007) Polzin D Veterinary Medicine discusses the significance of proteinuria.

Pet Place has a non-technical explanation of proteinuria (no need to register, just click on Close at the bottom of the irritating pop-up).

Antech Diagnostics discusses how to run and interpret tests for proteinuria.

The importance of proteinuria and microalbuminuria (2006) Scott SA Presentation to the World Small Animal Veterinary Association World Congress, discusses diagnostic methods for proteinuria.

 

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This page last updated: 06 November 2016

Links on this page last checked: 06 September 2016

 

   

*****

 

TREATING YOUR CAT WITHOUT VETERINARY ADVICE CAN BE EXTREMELY DANGEROUS.

 

I have tried very hard to ensure that the information provided in this website is accurate, but I am NOT a vet, just an ordinary person who has lived through CKD with three cats. This website is for educational purposes only, and is not intended to be used to diagnose or treat any cat. Before trying any of the treatments described herein, you MUST consult a qualified veterinarian and obtain professional advice on the correct regimen for your cat and his or her particular requirements; and you should only use any treatments described here with the full knowledge and approval of your vet. No responsibility can be accepted.

 

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