Let's look at how we manage cats with CKD and hypertension. I'm wondering, which is the anti-hypertensive drug that you have most experience using in cats? The drug that we have definitely been using for the longest and which has been shown to be highly efficacious for the management of hypertension in cats is amlodipine besylate.

This is a calcium channel blocker, and in fact its use was first reported in cats back in 1997. We are really lucky in veterinary medicine to have several anti-hypertensive drugs available for cats. In addition to amlodipine besylate, there is the angiotensin receptor blocker, telmisartan, which is also licenced as an anti-hypertensive agent for cats.

Historically, people have also used ACE inhibitors such as benazepril. However, although it's been shown in experimental studies that benazepril can decrease systolic blood pressure, in general, this reduction is really small, typically just 10 to 15 millimetres of mercury, and so it's not recommended as a first line anti-hypertensive treatment for cats. One of the advantages of amlodipine is that we have good evidence that it can effectively reduce blood pressure, not only in those cats that are in the hypertensive category, but also those cats that are in the severely hypertensive category.

So even when systolic blood pressure values can be over 200 millimetres of mercury. The evidence suggests that amlodipine can have a profound effect on blood pressure, but importantly, side effects such as hypotension, which is defined as an SVP of less than 120 millimetres of mercury, tend not to occur. So let's look at the mechanism of action of amlodipine, both systemically and also at the level of the kidney.

So here we have our cat from earlier, who has been treated for a week with amlodipine. Amlodipine besylate is a calcium channel blocker that causes arteriolar vasodilation, therefore decreasing systemic pressures. We can see our cat's systolic blood pressure has decreased from 180 to 130 millimetres of mercury.

Providing there has been adequate reduction in systemic blood pressures, the risk of transfer of high systemic pressures to the glomerulus will be reduced, therefore reducing glomerulocapillary pressures. As a consequence, we expect to see a reduction in the amount of protein crossing from the glomerulus to the tubular filtrate. At the level of the kidney, amlodipine besylate causes preferential afferent arteriolar vasodilation.

Because the relative vasodilation of the afferent arterial is greater than at the efferent arterial, there is no anticipated change in GFR, making amlodipine suitable for cats at all stages of kidney disease. So clinically when we start a cat on amlodipine, we expect to see a significant reduction in blood pressure. With a good response to treatment, we hope to reduce the risk of damage to the glomerulus and also reduce any hypertension induced proteinuria.

If we're starting a cat on amlodipine, what sort of reduction in blood pressure do you expect to see? Well, from the retrospective and prospective clinical studies, it's reported that you can see between a 30 to 70 millimetre mercury reduction in SBP when we start a cat on amlodipine treatment. And between 60 to 100% of cats will respond to amlodipine as a monotherapy, although sometimes we need a dose titration.

For ease of administration, I usually think about starting dose for amlodipine in most cats being 0.625 milligrammes per cat by mouth once a day, so that's half an Amodip tablet. I will usually recommend that cats are reevaluated after 3 to 10 days to have their blood pressure checked.

If SBP is still in the hypertensive category, so over 160 millimetres of mercury, then I will increase the dose of amlodipine to 1.25 milligrammes per cat once a day, i.e.

A whole Amadip tablet. If we have to increase the dose, then I will recommend that there is a further recheck to confirm that we have hit our target SBP of less than 160 millimetres of mercury. From clinical experience and published studies, the vast majority of cats will have good blood pressure control when managed in this way.

And from studies that have looked at the systolic blood pressure, at which we typically see ocular target organ damage, ensuring that SBP is less than 160 millimetres of mercury will substantially decrease this risk. It's interesting to note that there is data from a study by Beichmann and colleagues that indicates that there is an association between the initial blood pressure measurement and the likely dose of amlodipine that will be required. For cats where systolic blood pressure is over 200 millimetres of mercury, it's highly likely that the 1.25 milligramme per cat dose will be required.

A practical solution can therefore be to start these cats that have particularly high SBP on the higher dose from the outset. We have good clinical and previously published data that amlodipine can be a very effective treatment for these cats that are severely hypertensive. Rechecking SBP after starting treatment remains important.

To show that you have both reached the desired target for blood pressure control and to ensure that there's no evidence of hypotension. Rarely, probably in less than 5% of cats with systemic hypertension, a dose of up to 2.5 milligrammes per cat of amlodipine can be needed, equating to 0.5 milligrammes per kilogramme once daily, and very rarely a second agent might need to be considered.

But given how effective amlodipine is in these situations, it's important to ensure there are no compliance concerns before progressive dose escalation or second agents are used. Iris recommends assessing proteinuria as part of substaging of cats with CKD so this raises the question, when should we be evaluating proteinuria in a cat that has both hypertension and CKD? When we diagnose a cat with CKD, we are clearly going to have evaluated renal function, so your markers of filtration such as creatinine, SDMA, and urea, together with a urine specific gravity as an indicator of urine concentrating ability.

This is going to form part of your diagnosis of CKD. If you are performing a urine dipstick alongside the urine specific gravity, then this will give you some indication of whether or not proteinuria is likely to be present. Because dipsticks are only semi-quantitative, it's important to evaluate the degree of proteinuria alongside urine concentrating ability.

So for example, finding 2+ proteinuria is much more likely to be significant in a cat with a USG of 1012 than it is in a cat with a USG of 1030. However, ultimately, a urine protein to creatinine ratio is needed to fully quantify proteinuria and to perform iris substaging. But we know that in cats being hypertensive is likely to increase the magnitude of proteinuria.

Therefore, a practical and potentially cost saving option can be to only evaluate urine protein to creatinine ratio for substaging once that normattensive state has been achieved. Studies have shown that approximately 70% of hypertensive cats that have their hypertension controlled with amlodipine besylate will show some reduction in their level of hypertension induced proteinuria when they become norm attentive. For many of these cats, this will place them in either the non proteinuric or the borderline proteinuric substage category, and separate anti proteinuric therapy may not be needed.

This is likely to be the result of reduced glomerulocapillary pressures, secondary to reducing blood pressure. Where a cat is still persistently proteinuric after control of blood pressure, so has a urine protein to creatinine ratio that is persistently greater than 0.4, then we should consider specifically managing renal proteinuria.

A question that people often ask is whether diagnosing advanced, i.e., iris stage 4 CKD impacts decision making around anti-hypertensive treatment.

So sometimes we will diagnose cats with relatively late stage disease. By this I mean late Iris Stage 3 or Iris stage 4 CKD. And these cats can definitely be at risk of being more unstable.

We need to be a bit more cautious in these cats around administering anti-hypertensive drugs that could decrease GFR, for example, ACE inhibitors or angiotensin receptor blockers, but it's often a risk-benefit situation. Ideally, we would use a drug that is not going to reduce GFR further and risk deterioration in kidney function. Amlodipine can certainly be used in this situation, given that we don't expect any change in GFR or creatinine.

So irrespective of virus stage, amlodipine can be an effective anti-hypertensive agent. What should we take away in relation to and hypertension? We know that CKD increases the risk that a cat will be hypertensive.

So we should measure blood pressure in all cats with CKD and make an early diagnosis of hypertension. The kidney is a target organ for hypertensive damage. Controlling blood pressure enables us to protect the kidney from this injury.

Amlodipine is an effective monotherapy for treating hypertension in cats with all stages of CKD even those with severe hypertension. A practical tip to take away is that when we control blood pressure, we can see a decrease in hypertension associated proteinuria, so it can be helpful to substage for proteinuria once normalten is achieved. It can feel like a lot to clients when they find out that their cat has not just CKD but also hypertension.

Talking through what is going to be involved so that they can understand can really help to ensure we optimise care for cats with both CKD and hypertension together.