? Spike Prescribed Benazapril 2.5mg. For Increasing BUN. Is it Safe for Him.

Took Spike to the Vet this afternoon to address the past 4 days of vomiting at about the time he would be reaching the nadir of his Prozinc dose. The Vet didn't find anything wrong and said it was probably just a food issue as it does seem to mostly be related to being fed the chicken flavor.

She ran a lab and his BUN has increased to 53.3 mg/dl. Normal is 15.0 - 32.0
It was 48.1 on March 28th.
It was 43.6 on March 2nd. the date of his diagnosis of diabetic.

Vet prescribed 5mg tablet x 1/day for 30 days.

I just read that it can increase the risk of hypoglycemia in cats that are on insulin. Needless to say, I'm a little concerned about this. She said that this drug would help his kidney function and to continue using the AminAvast supplement ALONG WITH this new drug until the AminAvast runs out in several more days. The Vet said this is pretty standard procedure for cats with elevated BUN that aren't being helped by the AminAvast.

Any input that y'all can give would be appreciated. I haven't given him a dose of it yet as I kinda wanna hear what you and others think.

@FrostD
@Suzanne & Darcy

 

My Darcy was also prescribed Benazepril for his kidney function. I was very hesitant to use it. There are so many pros/cons. It kind of depends on what camp your vet is in. I did hours and hours of research on it. Let me link something for you for starters. It is most commonly prescribed for cats who are spilling protein into their urine, but many vets use it to help with kidney function. That increase in BUN is troubling, but your boy still eats like a sweet little piggy. Did she test creatinine or phosphorus or anything? Are you to recheck everything in 30 days?
I'll send the link in my next post.

 

Benazepril (Fortekor)

This is approved in Europe, Australia and Canada for the treatment of CKD in cats. If you are in the UK, I virtually guarantee you left the vet's clutching some therapeutic kidney food and some Fortekor.



Benazepril is actually a heart medication, and the evidence for its use in CKD is not particularly strong; plus in some cases, it may worsen bloodwork, at least initially. It can, however, be effective in treating a problem sometimes seen in CKD cats known as proteinuria (where protein leaks into the urine). Personally, I would use it in a cat with proteinuria, and I would probably use it for additional blood pressure control if amlodipine (mentioned above) was not sufficient, but I probably wouldn't bother with it otherwise.



See Proteinuria for more information.

 

Home > Key Issues > Proteinuria



Overview

• Proteinuria means there is excess protein in the urine. It is important to know if it is present because it may make CKD progress faster.
  

• It is also used to help 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, there will be excess levels of protein in the urine. This is called proteinuria.




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




According to ISFM consensus guidelines on the diagnosis and management of feline chronic kidney disease (2016) Sparkes AH, Caney S, Chalhoub S, Elliott J, Finch N, Gajanayake I, Langston C, Lefebvre H, White J & Quimby J Journal of Feline Medicine and Surgery 18 pp219-239, around 20% of CKD cats have obvious proteinuria. and 50-66% do not have it. The remaining 14-30% are borderline.





Pet Place has a non-technical explanation of proteinuria.




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




Why Proteinuria is Important





Proteinuria is important because it may make the CKD progress faster. Chronic kidney disease (CKD) in dogs and cats — staging and management strategies (2015) Chew D Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference states "Protein in urine is both a marker and a creator of more renal disease."




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




Types of Proteinuria

Proteinuria can have a number of possible causes, and treating the cause (if possible) may mean the proteinuria resolves. Treatment recommendations for CKD in cats (2019) International Renal Interest Society state "Cats in Stage 3 with urine protein to creatinine ratio (UP/C) >0.4 should be investigated for disease processes leading to proteinuria...Look for any concurrent associated disease process that may be treated/corrected”





Measurement and interpretation of proteinuria and microalbuminuria(2016) Grauer FG International Renal Interest Society explains more about the different types of proteinuria.



Pre-Renal


The proteinuria is caused by something other than the kidneys or urinary tract. Hypertension is one possible cause, according to Management of chronic renal failure: beyond the can(2001) Wallace MS Presentation to the Atlantic Coast Veterinary Conference.



Proteinuria and renal disease: a roundtable discussion (2005) mentions that hyperthyroidism may cause proteinuria.



Renal


The proteinuria is caused by the kidneys not working properly. Glomerulonephritis or amyloidosis may cause severe proteinuria, but Electrophoretic patterns of proteinuria in feline spontaneous chronic kidney disease (2020) Giraldi M, Paltrinieri S & Scarpa P Journal of Feline Medicine and Surgery 22(2) pp114-121 states "tubular proteins were significiantly more frequent in our population of cats with CKD compared with healthy cats at risk. This result supports the fact that the main pathological feature of feline (idiopathic) CKD consists in chronic tubular interstitial nephritis."



Post-Renal (Non-Renal)


The proteinuria is caused by a part of the urinary tract other than the kidneys depositing protein in the urine. Blood in the urine, infection or inflammation may give a false positive result, causing post-renal proteinuria.



Cornell University College of Veterinary Medicineexplains more about these issues.





How Proteinuria Damages Kidney Function




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 this also happens in cats.



Proteinuria(2013) Syme H Presentation to the 38th World Small Animal Veterinary Association World Congress states "Following loss of a critical amount of renal mass, hyperfiltration occurs in the remaining functional nephrons. Hyperfiltration occurs due to an increase in pressure applied to the glomerular filtration barrier, and this results in proteinuria. Ultimately, over time, this adaptive change may be detrimental ('maladaptive') and may result in interstitial fibrosis and inflammation resulting in further nephron loss, even in the absence of any extrinsic factors which damage the kidney (the so-called intact nephron hypothesis).



Proteinuria — what is this and why do we worry about it?(2014) Caney S Eukanuba Veterinary Diets Clinical Symposium 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.



Symptoms





One commonly seen symptom of proteinuria is foamy urine.



Proteinuria may also cause weight loss, and swelling in the legs, abdomen or face.




Diagnosis




Proteinuria is diagnosed via a urine sample. See Diagnosis for more information about obtaining urine samples.



Proteinuria and renal disease: a roundtable discussion (2005) is an interesting discussion by a number of veterinary specialists about proteinuria, and CKD generally, that includes a diagnostic algorithm.



Investigating proteinuric kidney disease(2007) Polzin D Veterinary Medicine discusses the significance of proteinuria.



Measurement and interpretation of proteinuria and microalbuminuria(2016) Grauer FG International Renal Interest Society states that the most commonly used method of obtaining urine to check for proteinuria is via the urine dipstick test but adds that "both routine-screening tests (dipstick and SSA) performed poorly and appear to be of minimal diagnostic value due to an unacceptable high number of false-positives. For both dipstick and SSA tests, the positive and negative likelihood ratios were close to 1 and the positive and negative predictive values were close to 50%, indicating that neither test provided useful information."



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 Medical 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.




Urine Protein:Creatinine Ratio (UPC)

The best way to test for proteinuria is via the urine protein:creatinine (UPC) ratio, which is also used to determine the severity of the proteinuria (see below).



The UPC test is available from Idexx Laboratories, which states "If the urinalysis is positive for protein and the sediment is not active, a urine protein:creatinine (UPC) ratio is automatically performed. If the urinalysis is negative for protein, or if there is an active sediment (white blood cells =6/hpf, red blood cells = 100/hpf, color is red or pink, and/or bacteria are seen), the UPC ratio will not be performed. The test price is the same whether or not a UPC ratio is performed."



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




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 +.



An update on the diagnosis and management of proteinuria in dogs and cats (2018) Idexx Laboratories has a very helpful overview of proteinuria and provides codes for its tests.



Cornell University College of Veterinary Medicine explains more about the diagnosis of proteinuria. It says "The urine protein results should always be interpreted in context with the urine specific gravity and pH. Normal urine contains little protein; negative to trace reactions are usual in concentrated urine (urine specific gravity > 1.025). A trace to 1+ reaction in a dilute urine (urine specific gravity < 1.015) is suggestive of significant proteinuria. A dipstick protein reaction > 2+ in concentrated or dilute urine indicates significant proteinuria."




Cut out and keep guide...diagnostic implications of proteinuria (2013) van Dongen A Veterinary Focus 23(3) pp47-48 explains more about the diagnosis of proteinuria.



Role of quantitative MA testing in everyday practice(2012) Harai B Antech Insights Aug/Sep 2012 discusses how to run and interpret tests for proteinuria.




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



Treatment recommendations for CKD in cats (2019) International Renal Interest Society suggest a biopsy is also necessary for "Persistent and severe proteinuria (UP/C>2.0) in a non-azotemic patient" or "Worsening proteinuria in a CKD patient."




Proteinuria Staging and Prognosis

IRIS staging of CKD(2019) International Renal Interest Society 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 UPC test in a number of different countries. 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




Treatment recommendations for CKD in cats (2019) International Renal Interest Society state "Changes in the magnitude of proteinuria should always be interpreted in light of the patient's blood creatinine concentration since proteinuria may decrease in progressive renal disease as the number of functional nephrons decrease. Decreasing proteinuria in the face of a stable blood creatinine suggests improving renal function, whereas decreasing proteinuria with increasing blood creatinine suggests disease progression."




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, do not 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




There are a number of possible treatments, some of which can be quite effective at reducing the level of proteinuria, but as yet there is little evidence that any of them may delay the progression of the CKD.



Reassessment of "normal" values in dogs and cats with chronic kidney disease(2019) Grauer GF International Renal Interest Society says "Current recommendations suggest that persistent proteinuria of renal origin of a magnitude > UPC of 0.4 in cats and > 0.5 in dogs with azotemic CKD should be treated with a renal diet and an angiotensin converting-enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB). Borderline proteinuria (UPC of 0.2 to 0.5 in dogs, or 0.2 to 0.4 in cats) warrants increased monitoring. Note, however, that borderline and even "normal" levels of proteinuria in cats have been associated with progressive disease."




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. These guidelines are now quite old, and whilst the basic information still applies, there is no discussion of newer treatments such as telmisartan.




Management of proteinuria in dogs and cats with chronic kidney disease (2016) Vaden SL & Elliott J Veterinary Clinics of North America Small Animal Practice 46(6) pp1115-30 discusses the treatment of proteinuria.

• • Diet
  • Stem cell transplants
  • Medications

Diet

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



Feeding a reduced protein but high quality protein food may be recommended. 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. 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."



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 following medications that may be used to treat proteinuria:

• ACE inhibitors, including benazepril (Fortekor) or enalapril (Enacard)
  
  Angiotensin II receptor blockers (ARBs), such as telmisartan (Semintra)
  
  • Which to use
    
    
  • Combining ACE inhibitors and ARBs
    
• Aspirin
  
  
• Beraprost (Rapros)
  

ACE Inhibitors

• What are ACE inhibitors?
  
  
• Using ACE inhibitors to control proteinuria
  
  
• Cautions, interactions and side effects
  
  
• Whether to use ACE inhibitors
  

What are ACE Inhibitors?

ACE inhibitors are heart medications which are commonly used to treat a heart condition called hypertrophic cardiomyopathy. They work by preventing the conversion of a hormone called angiotensin I into another hormone called angiotensin II, that plays a part in the development of proteinuria. The role of angiotensin II is to constrict blood vessels By preventing the conversion if ACEI into ACEII, 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. This may also reduce proteinuria.



ACE inhibitors are sometimes used to control hypertension (high blood pressure), and their use for this purpose is covered on the Hypertension page, though they are not usually considered the best choice for managing hypertension in cats.



The main reason they tend to be used i CKD cats is for reducing proteinuria.



Angiotensin converting enzyme (ACE) inhibitors (2017) Klabunde RE Cardiovascular Pharmacology Concepts explains how ACE inhibitors work.



Benazepril (Fortekor, Benazecare, Lotensin, Nelio)

One ACE inhibitor, benazepril, is approved for the treatment of CKD in cats in the UK, 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 website 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. You do not want Fortekor Plus, because it also contains another heart medication, pimobendan.



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)

Enalapril (trade name is Enacard) is another member of the ACE inhibitor family. This is excreted largely by the kidneys, so is not usually the best choice for a CKD cat. Benazepril, in contrast, 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) Langston CE Veterinary Medicine is a video presentation (video may no longer work properly). Dr Langston starts benazepril 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 in cats given benazepril when compared with cats given 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%)."



Since ACE inhibitors may sometimes lead to an increase in creatinine levels (usually temporary), some vets are reluctant to use them in later stage CKD cats. ACE inhibitors and CKD: the good, bad and ugly(2016) Grauer GF CVC in Kansas City Proceedings pp670-672 says "Use of ACEI in dogs and cats with serum creatinine concentrations greater than 5.0 mg/dl is usually not recommended." However, Treatment recommendations for CKD in cats (2019) International Renal Interest Society do not advise against using ACE inhibitors at any stage, saying "Cats in Stage 4 with urine protein to creatinine ratio (UP/C) >0.4 should be investigated for disease processes leading to proteinuria and treated with anti-proteinuric measures."



Although ACE inhibitors do reduce proteinuria in cats, it is not clear whether this makes a real difference to 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 proteinuria (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."



Benazepril (Fortekor) Dosing

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



When used to treat proteinuria in cats, 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 (5.5 - 11 lbs)

1 tablet

5.0 - 10.0 kg (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


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



ACE Inhibitors and 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."



Chronic kidney disease (CKD) in dogs and cats — staging and management strategies (2015) Chew D Presentation to the Virginia Veterinary Medical Association 2015 Virginia Veterinary Conference 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 hypertension in dogs and cats (2018) Acierno MJ, Brown S, Coleman AE, Jepson RE, Papich M, Stepien RL & Syme HM Journal of Veterinary Internal Medicine 32(6) pp1803-1822 say "Angiotensin converting enzyme inhibitors and ARB should not be started in dehydrated patients in which GFR [a measure of kidney function] may decrease precipitously. These patients should be carefully rehydrated and then re-evaluated before instituting ACEi or ARB treatment."



Treatment recommendations for CKD in cats (2019) International Renal Interest Society warn "The use of an RAAS inhibitor is contraindicated in any cat that is clinically dehydrated or is showing signs of hypovolemia. Correct dehydration before using these drugs otherwise glomerular filtration rate may drop precipitously."



Proteinuria (2013) Syme H Presentation to the 38th World Small Animal Veterinary Association World Congress 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.



ACE Inhibitors Effects on Potassium Levels and Anaemia


The use of ACE inhibitors may lead to an increase in potassium levels in the blood, which could be a risk in a cat who already has high blood potassium levels. Drugs discusses this.



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."



However, Renal dysfunction in small animals (2013) Brown SA Merck Veterinary Manual states "If an ACE inhibitor is used in conjunction with a renal diet, potassium should be carefully monitored. Hyperkalemia may develop, particularly in Stage 4, and dietary change or dosage adjustment should be considered if serum potassium exceeds 6.5 mEq/L."



Treatment recommendations for CKD in cats (2019) International Renal Interest Society advise against the use of ACE inhibitors when potassium is over 5 mEq/L.



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.



ACE Inhibitors 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.



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”.



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."




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." Treatment recommendations for CKD in cats (2019) International Renal Interest Societysay "there is at present no evidence that intervention with anti-proteinuric drugs slows progression."



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 benazepril) 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."



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 talk to your vet.

 

I really should have just linked you to the page on felinecrf.org. This is a very well-researched and documented website (and the support group for kidney disease is excellent.) I did, however, do a lot of my own research and finally decided to give Darcy the Benazepril. He died of complications related to kidney disease, but not from the kidney disease itself. I am in love with your Spike just from looking at his photo.

Next time you are at the vet, make SURE that they check his blood pressure. High blood pressure is dangerous and is common in cats with kidney disease. Then in 30 days after he starts the Benazepril, run bloodwork and a urinalysis and check the Blood Pressure.

 

Thank you for all of this info. And to think, my first main concern was if a half of a 5mg pill was gonna knock Spike into hypoglycemia when 8 give it to him after his insulin shot.

Did you have any bg issues with using the drug along with giving insulin? I think I'll start him on the half a 5mg. pill this evening rather than In the AM, as I work days and can't monitor. Luckily, it's Friday, so I'll have all weekend to see what's gonna happen before the new workweek starts.

I have a printout of the comprehensive lab results and will enter it into the lab section on the SS later today.

The Vet seemed to like his other results. His bg was 384 at the office.
BUN/Creatinine ratio is 31.4
Creatinine is 1.7 mg/dl Norm Range 0.8 - 1.8
Phosphorus is 5.4 mg/dl Normal Range 2.6 - 6.0

I'm just scared it'll knock him into hypo.

 

I do not think it will cause him to hypo. But every cat is different so I am happy you will be home thos weekend!

 

Well Suzanne gave you the full dissertation, not much left for me to add LOL