State-of-the-Art Lecture Update on the Diagnosis and Management of Acute Kidney Injury in the Dog
The term “acute kidney injury” (AKI) has been adopted in recent years in both human and veterinary medicine and replaced the old term “acute renal failure.” The term AKI is more accurate, as not every injury is associated with a measurable failure. The new terminology also sensitizes clinicians to early identification and intervention. Currently, an increase in serum creatinine concentration as little as 0.3 mg/dL or decreased urine production for more than 6 hours is classified as AKI, even if concentration creatinine is still within the reference range. Yet, in many animals, the baseline creatinine concentration is unknown at presentation and urine production is not quantified. Thus, any animal with acute onset of clinical signs, increased creatinine concentration, low urine specific gravity, without any evidence of previous chronic kidney disease, should be suspected for AKI until proven otherwise. Presence of urinary markers such as glucose or casts might aid in the diagnosis, however, these are present only in ∼ 30% of the cases, thus are insensitive. Novel sensitive and specific biomarkers are currently under investigation.
The most common etiologies for AKI in dogs can be categorized as follows:
1. Nephrotoxicity, including endogenous nephrotoxins (e.g., hemoglobin, myoglobin) and exogenous nephrotoxins, including ethylene glycol, lilies (cats), grapes and raisins (dogs), medications (e.g., gentamicin) and contrast agents.
2. Infectious agents: leptospirosis, pyelonephritis, sepsis, and FIP in cats.
AKI is a systemic disease affecting many body organs, thus the treatment should be focused on the whole patient rather than on the kidney alone. The treatment should focus at identification and elimination of any inciting causes (if possible), controlling the ensued clinical signs and clinicopathologic abnormalities (i.e., retention of uremic toxins, acid-base and electrolyte disorders, changes in blood pressure, decreased erythropoietin production) as well as addressing complications (e.g., respiratory disorders, pancreatitis, disseminated intravascular coagulation etc.). The goal is to maintain homeostasis and control clinical signs until the kidney recovers.
Animals with AKI are often dehydrated at presentation but may also be overhydrated, mostly due to previous medical treatment that included excessive fluid administration. Although changes in hydration and volemia often parallel, there are some exceptions. An overhydrated patient may be hypovolemic and vice versa. Assessment of hydration status is based mostly on the patient’s skin turgor and the mucous membranes, however in patients with uremia this assessment is often challenging. Uremia can lead to decreased saliva production and dry mouth (xerostomia) or alternatively to nausea and salivation. There are only a few objective measures that can be used to assess the hydration status. The most readily available tool to assess changes in hydration status is serial measurements of body weight.
The initial treatment should focus in correcting the patient hydration status. Unless there is a contraindication for rapid fluid administration (e.g., heart disease), dehydration should be corrected over 4–6 hours, using the following formula:
Volume (L) = Body weight x % Hydration
When calculating the amount of fluids to be administered thereafter, one has also to consider urine production, ongoing losses, and insensible losses. The maintenance requirements of patients with AKI cannot be extrapolated from the required maintenance fluids of normal patients, as some of the AKI patients are an/oliguric while others are polyuric. Therefore, fluid rate should be adjusted individually for each patient.
Patients with AKI should be weighed at presentation and routinely during the treatment period. Once a patient has reached its goal weight, it should be maintained on this weight throughout the hospitalization time. Fluid rate is determined by the rate of fluid loss (urine production, insensible losses and ongoing losses). Fluid administration without close monitoring may result in life threatening overhydration, especially in those patients with low urine production that cannot excrete the fluids administered. Clinical signs of overhydration include serous secretions from the nose, peripheral edema, lung edema, chemosis, pleural effusion and ascites. Overhydration is a common cause for morbidity and mortality in patients with AKI.
Recovery from AKI is often associated with the transition from anuria/oliguria to polyuria. This is a critical point, in which the risk for dehydration is high, and consequently further damage to the kidneys may occur. Polyuric patients may lose a substantial amount of fluids and typically do not drink enough to compensate for the fluid loss, thus fluids have to be administered as needed to maintain normal hydration status.
Once the animal has reached normal hydration status and urine production is still low, the use of diuretics should be considered. Under no circumstances should diuretics be used to promote urine production in a dehydrated patient. The most commonly used diuretics are mannitol, furosemide and dopamine. Despite their wide use, there is no solid scientific evidence to advocate their use. In addition, like any other drug, diuretics may be associated with side effects, therefore their use should be considered for each case individually.
Mannitol is an osmotic diuretic; therefore, it is active along the entire nephron. Mannitol increases urine production, blood flow to the kidney, and promotes urea excretion. Mannitol is also a free radical scavenger. It is administered initially as a bolus (0.5–1.0 g/kg over 20 minutes) which is followed by a constant rate infusion at 1 mg/kg/min. Prior to mannitol administration blood pressure should be controlled, as mannitol may increase the intravascular volume and worsen hypertension.
Furosemide is a potent loop diuretic, which acts on the thick ascending loop of Henle. Furosemide increases the blood flow to the kidney and promotes urea excretion, but it does not have any effect on the glomerular filtration rate. Furosemide is administered as an initial bolus or as a constant rate infusion. In addition to its diuretic effect, furosemide promotes potassium excretion.
The use of dopamine is highly controversial, both in human and veterinary medicine. The recommended dose for AKI is a low (0.5–3.0 µg/kg/min), which, at least in theory, activates only the dopaminergic receptors without activation of α and β adrenergic receptors. Recent studies performed in human medicine demonstrated that although dopamine can increase urine production in some patients with AKI, its use did not change the outcome of these patients (death or the need for dialysis). Fenoldopam is a selective dopaminergic agonist which has been shown to promote urine production and solute excretion in normal animals but in a recent study did not change the outcome or kidney dysfunction in animals with heatstroke related AKI.1
Controlling Clinical and Clinicopathologic Signs Associated with Uremia
Gastrointestinal signs result from a direct effect of the uremic toxins on the chemoreceptor trigger zone and from gastrointestinal damage caused by these toxins (e.g., ulcers). The control of gastrointestinal signs is achieved by the use of gastrointestinal protectants (H2 blockers, proton pump inhibitors) and antiemetic medications (e.g., metoclopramide, ondansetron, maropitant).
Metabolic acidosis is a common acid-base disorder of patients with AKI. Metabolic acidosis results from retention of acids in the blood, decreased bicarbonate reabsorption in the proximal tubule, decreased bicarbonate production and decreased hydrogen excretion. Correction of dehydration will eliminate lactic acidosis but patients that remain acidotic need to be treated with bicarbonate, as follows:
HCO3 (mEq) = 0.3 x Body weight (kg) x Base deficit
Treatment should be performed cautiously and over a few hours. Rapid bicarbonate administration may lead to paradoxical cerebellar acidosis or metabolic alkalosis.
Hyperkalemia is a common complication of patients with AKI, which results mostly from decreased renal potassium excretion and acidosis. The treatment is determined by the severity of the hyperkalemia and the degree of cardiotoxicity. In mild cases, potassium-free fluids may correct hyperkalemia. In more severe cases dextrose (with or without insulin) and bicarbonate administration are used to shift the potassium intracellularly. When cardiotoxicity is already present, calcium is indicated to protect the heart.
Hypertension is a common complication in AKI. Hypertension may cause severe damage to end organs (eyes, heart, kidneys and brain). In most cases treatment with the calcium channel blocker (e.g., amlodipine) controls hypertension. In refractory cases, hydralazine and nitroprusside can also be considered. Angiotensin converting enzyme inhibitors are recommended as part of the management of hypertension in patients with chronic kidney disease, but should be carefully considered in cases of AKI as they may further decrease GFR and worsen azotemia.
1. Segev G, Bruchim Y, Berl N, Cohen A, Aroch I. Effects of fenoldopam on kidney function parameters and its therapeutic efficacy in the management of acute kidney injury in dogs with heatstroke. J Vet Intern Med. 2018;32(3):1109–1115.