DVM: Your experience with diagnosing and treating acute renal failure is extensive given your position as an assistant professor of small animal internal medicine at Purdue University and your special interest in areas of renal disease. Can you describe some of the most common presentations in dogs vs. cats?
DVM: Do these patients often present with concurrent disease conditions?
Pressler: Many patients with acute renal failure have additional diseases or conditions diagnosed at the time of presentation. These concurrent conditions may be the cause of their acute renal failure — for example, pancreatitis, heart failure or hypoadrenocorticism — or may be consequences of the same conditions that resulted in kidney damage as in the case of disseminated intravascular coagulopathy (DIC). Concurrent conditions may also have developed secondary to the renal failure itself, as in the case of pulmonary edema, pancreatitis, hypovolemic or hypotensive shock or pancreatitis. In general, cats seem less likely to have most of these concurrent diseases, but, on the contrary, they are more likely to have infiltrative renal disease such as lymphoma or feline infectious peritonitis (FIP) or ureteral obstruction as a cause of their renal failure.
DVM: How do you approach diagnosis in suspected cases of acute renal failure?
Pressler: Acute renal failure, by definition, is at least partially reversible with aggressive therapy. Therefore, diagnosing the underlying cause of kidney disease offers the best chance of preventing damage from progressing via targeted therapy on top of aggressive general support. Naturally, I always start with a thorough history and physical examination. I never ask owners if their pets could have gotten into any toxins because many people do not know that some common household plants and drugs can result in kidney disease. Instead, I run through a list of possible toxins with owners one by one and ask individually about lilies, NSAIDs, grapes, etc. I treat all dogs with acute renal failure for leptospirosis while awaiting results of serum titers, both because this disease is prevalent throughout most of the United States and because of the zoonotic risk. I also culture urine immediately, regardless of urine sediment findings, in the event that renal failure is due to pyelonephritis. Finally, I always include abdominal imaging in my diagnostic evaluation of patients with acute renal failure in order to diagnose infiltrative diseases such as lymphoma or FIP or to detect ureteral obstructions.
DVM: What are the most important treatment concerns when a dog presents with acute renal failure?
Pressler: The importance of correcting and continually monitoring hydration status cannot be overstated in any patient with acute renal failure. Many patients are dehydrated at the time of first presentation. Aggressively replacing any fluid deficits (usually over the course of just a few hours) is required to normalize renal blood flow; this allows urine production that will hopefully unclog nephrons that have become obstructed by damaged, sloughed cells; provides oxygen to injured and healing tubules; and maintains blood flow to the renal medulla, which is highly sensitive to hypoxemic damage. Patients with acute renal failure must be serially monitored to ensure that the intravenous fluid rate is sufficient to maintain hydration. Remember that "two-times-maintenance" is based on maintenance for that animal being that of a healthy animal. Constant reassessment of body weight, skin turgor and urine output often leads to adjustments in fluid rate multiple times a day. I also measure central venous pressure if possible as a more objective measure of hydration status.
DVM: How does that differ in cats?
Pressler: Cats with acute renal failure do not differ from dogs in their need for aggressive fluid support, although mild fluid overload is much more likely to result in heart failure and pulmonary edema than in dogs. This may be because cats are more likely to have occult heart disease than dogs.
DVM: Do you have specific recommendations for handling the secondary GI signs seen with renal failure (e.g., inappetence, GI ulceration)?
Pressler: When a patient with intrinsic renal disease is displaying signs referable to the GI tract — in other words, vomiting — I always treat for presumptive GI ulceration. Oral H2-blockers such as famotidine are available without a prescription, are well-tolerated and are not costly. If this class of drugs fails to resolve the observed clinical signs, then I usually re-examine the patient for other possible causes before attempting another drug. If further gastroprotection is required, I typically opt for a proton-pump inhibitor such as omeprazole and reserve sucralfate for patients with obvious GI bleeding as exhibited by hematemesis or melena.
DVM: Is mirtazapine useful in this area?
Pressler: Inappetence secondary to nausea in uremic patients is presumptively due to both stimulation of the medullary chemoreceptor trigger zone by uremic toxins and peripheral GI ulceration and enteritis. The precise mechanism whereby mirtazapine prevents nausea is unknown. One effect in people appears to be inhibition of 5-HT3 serotonin receptors within the chemoreceptor trigger zone, so I do believe that mirtazapine could, in theory, be beneficial for treating renal failure-associated nausea. That being said, I have had mixed success in dogs with chronic kidney disease but still believe a trial course is appropriate if other treatments have been unsuccessful. I do worry, however, about the lack of studies on this drug in dogs and cats, as we know very little about possible side effects or drug interactions. For example, mirtazapine is eliminated primarily in the urine in people, and dose reductions are recommended in patients with kidney failure.
DVM: Would you describe how you address hypertension in patients with acute renal failure? Does the presence of hypertension change your treatment progression?
Pressler: To begin with, it needs to be emphasized that hypertension is a common consequence of renal failure, so measurement of blood pressure should be a routine part of the initial evaluation and all recheck examinations in patients with kidney disease. Persistent hypertension is associated with shortened time until uremic crisis and reduced survival in patients with chronic kidney disease. Treatment is thus recommended with the hope that normalization of blood pressure will delay progressive nephron damage.
In dogs, angiotensin-converting enzyme (ACE) inhibitors lower blood pressure, reduce proteinuria and may provide additional anti-inflammatory and antifibrotic benefits. If hypertension persists despite a maximal dose of ACE inhibitors, then I add amlodipine. I always start this second drug at the lowest recommended dose because there is a synergistic effect, and hypotension may occur.
In cats, amlodipine is highly effective in treating hypertension in patients with kidney disease. ACE inhibitors are rarely effective at lowering blood pressure in cats, proteinuria is much less common and there is less evidence for dysregulation of the renin-angiotensin-aldosterone system that would presumptively benefit from ACE inhibitors.
DVM: Does the use of telmisartin seem promising for treating hypertension?
Pressler: Angiotensin II receptor antagonists such as telmisartin or losartan are commonly used antihypertensives in people. These drugs directly inhibit the action of angiotensin II, a potent vasoconstrictor, and may provide superior blockade of the renin-angiotensin-aldosterone system than ACE inhibitors do. These drugs also prevent the phenomenon of aldosterone escape seen with chronic ACE inhibitor therapy, which refers to the increases in aldosterone to pretreatment concentrations. Unfortunately, these drugs are relatively costly, doses in veterinary patients have not been established, and it is unknown how or if these drugs alter prognosis in dogs with glomerular or chronic kidney disease. I believe these drugs will eventually become a routine part of our antiproteinuria therapy, but I am wary of using them as first-line anti-hypertensives until further efficacy and safety studies are performed.
DVM: Finally, do you have a particular protocol for addressing renal secondary hyperparathyroidism?
Pressler: The first step in treating renal secondary hyperparathyroidism is normalizing the serum phosphorus concentration, as hyperphosphatemia increases serum parathyroid hormone (PTH) concentrations. This is best done first by transitioning to a renal-formulated diet. If the serum phosphorus concentration is still increased or in the upper end of the reference range, then an oral phosphate binder should be administered; I most commonly use nonflavored, powdered aluminum hydroxide. Only once phosphorus has reached this target do I measure serum PTH concentrations in patients with azotemic chronic kidney disease. If the concentration is increased, then it is the most likely cause of decreased active vitamin D production by the diseased kidneys, and calcitriol should be considered.
DVM: Specifically, how and when do you use calcitriol?
Pressler: I personally consider calcitriol only in those patients with chronic kidney disease in which the PTH concentration is increased despite the serum phosphorus concentration being in the lower half of the reference range. However, I always balance prescribing calcitriol with a number of other factors, including whether the owner has demonstrated good compliance with previous medications since calcitriol has a low safety margin and errors in administration can have severe consequences. I also consider the owner's financial situation because visits for measurement of serum PTH and ionized calcium concentrations to determine appropriate dosing can be costly. The last consideration is the rate of disease progression in the patient.
Unfortunately, the true benefit of calcitriol administration has not been determined as of yet through prospective studies, so the veterinary nephrology community is still not unified as to when and how best to incorporate calcitriol in the management of patients with chronic kidney disease. For example, azotemic patients with normal serum PTH concentrations still have intracellular biochemical alterations consistent with renal secondary hyperparathyroidism. However, although this does suggest that earlier use of calcitriol than what I suggest could eventually prove to be beneficial, in most nephrologists' opinions, these are outweighed at this time by the safety and cost considerations I outlined above.
DVM: Thank you, Dr. Pressler, for your time and detailed answers regarding several controversial areas of renal disease treatment. There are always new avenues of interest coming out of human medicine, and only time and research will tell if they prove to be effective treatments for small animals.
Editor's note: Barrak Pressler, DVM, PhD, Dipl. ACVIM, is an assistant professor of small-animal internal medicine at Purdue University in West Lafayette, Ind., where he is the principal investigator in the Comparative Nephrology Laboratory. His main clinical and basic science interests are veterinary nephrology and urology, particularly the pathogenesis and immune dysfunction of glomerular and autoantibody diseases. He has published multiple research articles in these fields and is a Veterinary Medicine editorial advisory board member.
Dr. Blake is a freelance technical editor and writer in Eudora, Kan.