Acute renal failure (ARF) is a syndrome characterised by sudden onset of filtration failure by the kidneys, accumulation of uraemic toxins, and dysregulation of fluid, electrolytes and acid-base balance. It is potentially reversible if diagnosed quickly and treated aggressively. Azotaemia is defined as an elevation in blood urea nitrogen (BUN) and creatinine. The serum urea nitrogen is usually severely elevated in an azotaemic rabbit, whereas the creatinine may only be mildly elevated. One reason for this is thought to be the rabbit's decreased muscle mass compared to that of dogs and cats. ARF is initiated by ischaemia, nephrotoxins or intrinsic renal disease. The primary objective for treating the ARF patient includes attempts at reestablishing urine flow and treatment of the precipitating event.
Examples include shock, hypovolaemia, decreased cardiac output and sepsis. It is often possible to distinguish animals with prerenal azotaemia from those with intrinsic ARF using history and clinical findings. The presence of mild to moderate azotaemia, clinical dehydration, hypovolaemia or hypotension, in conjunction with a concentrated urine specific gravity (USG) (USG >1030) confirms a diagnosis of pre-renal azotaemia. Therapeutic confirmation of the diagnosis can be made by a rapid resolution of the azotaemia with restoration of fluid balance and normalisation of systemic haemodynamics.
The most common causes of postrenal azotaemia include partial or complete obstruction of the urethra or bladder by uroliths, blood clots or sand and mucous plugs.
Intrinsic Renal Disease
This may be glomerular nephritis, tubular damage or interstitial renal disease. Causes include:
Drugs. Aminoglycosides, chemotherapeutics, radiographic contrast agents, ethylene glycol, heavy metals and diuretics can cause direct tubular damage. Non-steroidal antiinflammatory drugs (NSAIDs) are commonly used in rabbits to treat inflammatory conditions and pain. NSAIDs inhibit cyclo-oxygenase (COX)-dependent synthesis of vasodilatory prostaglandins that regulate renal blood flow when renal perfusion is compromised. Non-selective COX-1/COX-2 inhibitors (e.g., flunixin meglumine, ibuprofen, aspirin) promote loss of counter-regulatory vasodilation to an ischaemic insult, which intensifies vascular resistance and furthers hypoperfusion of the kidney. The newer NSAIDs, which are primarily COX-2 inhibitors (e.g., meloxicam, carprofen, deracoxib), also have the potential to be nephrotoxic. The author recommends that NSAIDs are not to be given to poorly perfused, dehydrated or azotaemic rabbits. Correction of perfusion deficits, dehydration and azotaemia must be done prior to using NSAIDs.
Infectious diseases such as Encephalitozoon cuniculi can cause interstitial nephritis. Rabbits may present with neurological signs and acute or chronic renal failure.
The clinician must differentiate chronic renal failure from ARF because ARF is potentially reversible while chronic renal failure is not reversible. Both acute and chronic renal failure will show laboratory data with elevations in BUN and creatinine. In chronic renal failure there is a history of chronic loss of body condition, polydipsia and polyuria, and laboratory findings of anaemia. In the author's experience, ultrasound evaluation of the kidneys in chronic renal failure shows small kidneys (measuring less than 3 cm in length x 2 cm in width) with poor architecture. In ARF the animal will usually have a normal body condition and no history of polyuria and polydipsia. There is usually a normal haematocrit in ARF. Other diagnostic tests such as a urinalysis (± culture and sensitivity) to rule out infection and E. cuniculi serology, should be done in suspected cases.
Treatment For ARF
Correction of Perfusion Abnormalities
Correct perfusion abnormalities when hypotension (i.e., systolic blood pressure <90 mmHg) is present. Crystalloid fluids are initially given at 15-20 ml/kg boluses with 3-5 ml/kg hetastarch to correct perfusion parameters. In some cases, Oxyglobin® may be used in the difficult-to-resuscitate patient. Heat support is used when the rabbit is hypothermic.
As a guide to the volume of fluid required to rehydrate an animal, calculate hydration deficit and multiply by body weight in kilograms. A 2 kg rabbit that is 10% dehydrated will require 2 x 10/100 litres = 200 ml of fluid to correct the deficit. Administer this volume over a short period of time of 6-8 hours (e.g., 25-33 ml/hr for 6-8 hours in a 2 kg rabbit). Once the animal is normotensive and rehydrated, record the volume of urine produced every 4 hours. This is the polyuric or diuresis phase of ARF. Measurement of urine volume can be accomplished by continuous urinary bladder catheterisation or by placing preweighed diapers under the vulva or penis. The volume of urine voided on the diaper can be estimated by assuming 1000 ml equals 1000 grams. The volume of fluid to be administered in each 4-hour period is the sum of calculated maintenance requirements (2 ml/kg/ hr) and urine volume for the previous interval. Even weighing the rabbit twice a day can provide insight into how effective (or ineffective) your fluid therapy is. If the rabbit has lost weight, then your replacement fluid therapy is ineffective. Ongoing losses (e.g., diarrhoea) also must be estimated and added to the volume of fluids administered; it is safe to assume that most patients with ARF become 3-5% dehydrated each day as a result of ongoing losses. Therefore, increase the final calculated volume of fluids administered by 3-5%. In many instances, once the polyuric phase of ARF occurs, such large volumes of urine are produced that only aggressive fluid administration will allow you to keep up with your patient's fluid requirements. The urine production may be as high as 5-10 ml/ kg/hr, which is added to maintenance fluid requirements and ongoing losses (i.e., 5-10 x maintenance requirements may be required during the diuresis phase). Rule-of-thumb replacement using 2-2.5 times maintenance fluids for diuresis is ineffective and will lead to dehydration and ineffective urine production. Fluids should be gradually discontinued when hydration and urine production are restored (fluids in and urine out are matched), serum urea and creatinine are normal (stabilised) and the patient is eating and drinking. Taper the fluids by 50%/day. The taper of fluids will prevent medullary washout.
Use of force feeding can be attempted, but in the author's experience sick rabbits with ARF will refuse syringe feedings. Use of a nasogastric tube with a fibre diet is recommended.
Hyperphosphataemia and Hypercalcaemia
The major site of excretion of phosphorus is the kidneys. In the author's clinic most rabbits have higher ionised calcium than that seen in domestic animals. The most serious consequences of hyperphosphataemia are hypercalcaemia and tissue deposition of calcium salts potentially causing dysfunction of organs such as the kidneys and the heart. Therapy consists of fluid diuresis and oral phosphate-binding agents (Amphogel 90 mg/kg/day via nasogastric tube or orally) once the rabbit is eating or being fed through the use of a nasogastric tube.
Discontinue any drugs that may have caused the ARF (i.e., NSAIDs, aminoglycosides, etc). Treat urinary tract infection with enrofloxacin (15 mg/kg orally q24h) pending a urinary culture and sensitivity.
Treat for E. cuniculi if suspected and especially when neurological signs are present with ARF.