Urinary diseases of exotic pets (Proceedings)

Urinary diseases are frequently encountered in exotic animal pets and an understanding of the renal physiology and pathology of these diseases is important for effective treatment. Several factors contribute to the development of these problems including the anatomy and diet of these animals.

Rabbits and guinea pigs

The renal architecture in rabbits and rodents is unipapillate, with one longitudinal papilla and one calyx directly entering each ureter. The ureters empty into the urinary bladder which is flaccid in rabbits when empty and three times more distensible than the feline urinary bladder. Urine empties from the urinary bladder via the urethra, which in rabbits is the approximate size of a human child. Rabbits have unique calcium metabolism in that calcium homeostasis is regulated by the kidneys. Absorption of dietary calcium is passive and independent of vitamin D. Total blood calcium levels are often high and variable as a result. Urine is a major route of calcium excretion for rabbits (45-60% compared to <2% in other mammals). An increase in dietary calcium directly corresponds to increases in urinary excretion of calcium. As herbivores, rabbits and guinea pigs produce urine that is alkaline (pH 8.0-8.2) and has a thick cloudy appearance due to crystals formed by calcium carbonate precipitates in rabbits and calcium oxalate precipitates in guinea pigs. Urine turbidity may be variable depending on the amount of dietary calcium ingested, hydration status, health, age, and reproductive status of the animal. Urine color can vary from yellow, orange, brown, or red depending on diet and plant pigments excreted. Red urine often results from eating dandelion, broccoli, cabbage or beets and may be mistaken as blood.

A degree of calciuria is normal in rabbits and guinea pigs, however excess calcium precipitate or decreased fluid output results in thick paste, or sludge. Calcium sludge accumulates in the urinary bladder resulting in cystitis, and causes urethral irritation when urinated. Urolithiasis is the formation of calculi in the urinary tract and may be unrelated to calciuria. Uroliths may be renal, ureteral, cystic, or urethral. Urolithiasis in rabbits is related to their high calcium excretory rate but also may be the result of mechanical obstruction of the urinary tract. Urine retention leading to stone formation can be caused by adhesions, abscesses, tumors, and urine sludging. Non-obstructive factors including genetics, dehydration, inactivity, obesity, urine retention, cystitis, and changes in urine pH may also predispose rabbits and guinea pigs to urolithiasis. Cystitis secondary to Streptococcus pyogenes is a predisposing factor in guinea pigs. Small mammals with urolithiasis or hypercalciuria often have a history of limited exercise, making them prone to obesity, and a diet of free-choice pellets and alfalfa hay, which is high in digestible calcium. Clinical signs of urine sludging secondary to excessive calciuria and urolithiasis include dysuria, stranguria, depression, painful hunched posture, teeth grinding, urinary incontinence, urine scald (perineal dermatitis), polyuria, and polydypsia. Anorexia and hematuria may also be present.

Physical examination is an important part of the diagnosis of urinary disease. Calcium sediment is sometimes palpable in the urinary bladder of rabbits with urine sludging. Uroliths might be palpable in the bladder but are often too small. Kidneys can be enlarged in cases of hydronephrosis. Dried sludge may be apparent in the fur on the hindquarters or around the urogenital area. Radiographic evaluation of the patient will demonstrate radio-opaque stones within the urinary tract or sediment in the urinary bladder. Patients with multiple stones may be difficult to evaluate radiographically, requiring ultrasound to detect multiple small stones. A more thorough evaluation of the kidneys can also be performed through ultrasonography evaluation. Routine urinalysis should be performed when hypercalciuria or urolithiasis is suspected. Urine specific gravity in rabbits is 1.003-1.036 but may be difficult to measure due to the presence of crystals. Herbivore urine is normally alkaline and may contain trace protein and glucose normally. Microscopic evaluation of sediment will help detect crystals, red blood cells, inflammatory cells, and bacteria. It is important to note that hematuria in females may be urinary or reproductive in origin (urine collection via cystocentesis will differentiate between these). If bacteria are present, culture and sensitivity testing is indicated. Routine hematological evaluation will provide screening for systemic disease including infection, anemia, kidney function, hepatic health, and blood calcium levels.

Identification and correction of predisposing factors is needed for therapy to be effective. Supportive care including wound management, grooming, analgesia using a combination of opioids (buprenorphine 0.03 mg/kg SQ q 6-8 hrs) and NSAIDS (meloxicam 0.3 mg/kg PO q 12 hrs), and antibiotic therapy should be implemented as needed. Antibiotic therapy should be based on culture results but enrofloxacin (5-20 mg/kg q 12 hrs) and trimethoprim-sulfa (15-30 mg/kg q 12 hrs) are good empirical choices. Urinary sludging is managed in several ways. Initially, the urinary bladder should be expressed to clear retained sediment. This may be quite painful and the patient often needs to be sedated or anesthetized for the procedure. Diuresis will lead to rehydration of the patient and increased fluid content of the urine, diluting calcium crystals. Treatment of urolithiasis depends on the patient's health, location of calculi, and size of calculi. Surgery is generally indicated for the removal of large calculi as these will not resolve on their own. A cystotomy is the treatment of choice for any calculi in the bladder. A surgical spoon should be used to facilitate small stone removal to avoid lodging in the urethra, whereas flushing and suction can help rid the bladder of any fine granules. Cultures of the bladder wall and the stone itself should be obtained. A nephrectomy may be necessary if there are any stones in the renal pelvis causing obstruction and hydronephrosis. The prognosis for this procedure is guarded due to a higher risk of post-surgical complications. Presurgical evaluation of the kidney enzymes is prudent. Smaller calculi may be treated with catheterization and flushing to remove the stones from the urinary bladder or urethra. This non-surgical approach involves administering fluids to increase the flushing action of the urinary tract. Expressing the bladder to encourage emptying will increase the efficacy of this method. Catheter placement is done under anesthesia and the bladder infused with saline. The fluid is then suctioned out and the procedure repeated until the sludge is reduced.

Increasing water consumption is arguably the most important factor in preventing hypercalciuria or urolithiasis. Initial diuresis with intravenous, subcutaneous, or oral fluids should be implemented. Feeding succulent leafy greens such as kale, mustard greens, dandelion greens, and parsley and adding natural fruit juices without sugar to the water encourage water intake over time. Limiting dietary intake of calcium is also important. Feeding pelleted food formulated from grass hay and limiting exposure to alfalfa hay is recommended. Vitamin and mineral supplements should be discontinued. Exercise and grazing will promote water intake and frequent urination. Potassium citrate has been advocated by some as a means to prevent calcium oxalate urolith formation (Rabbits – 33 mg/kg PO q 8 hrs, Guinea pigs – 10-30 mg/kg PO q 12 hrs). The citrate salt is highly soluble and complexes with the calcium reducing the urinary concentration of calcium oxalate. Potassium citrate is also a urine alkalinizer which helps to increase the solubility of calcium oxalate resulting in less sedimentation. Long term management including urine analysis performed regularly to monitor for infection or mineral formation and radiographs to assess new calculi formation are indicated every 6 months. 

Birds and reptiles

The urinary tract of birds is anatomically simple, with two kidneys, two ureters, but no urinary bladder. The kidneys are located bilaterally against the dorsal body wall in the renal fossa. Each kidney has three segments; a cranial, middle, and caudal pole. The ureters have branches from all three kidney lobes and extend from the kidneys caudally to the urodeum of the cloaca. Renal products include uric acid and urine due to the distribution of both mammalian and reptilian nephrons within the renal parenchyma. Reptiles also have simple urinary systems comprised of the kidneys and ureters bilaterally. In lizards, the kidneys are situated in the caudal coelom protected by the pelvic canal. These are often palpable when enlarged due to renal disease. The kidneys in chelonians are dorsal in the caudal coelom and in snakes are in the caudal 1/3 of the body. The kidneys eliminate uric acid through tubular secretion from reptilian nephrons which lack a loop of Henle. Lizards and chelonians, but not snakes, possess a urinary bladder that connects directly to the cloaca. Urine entering the cloaca from the ureters enters the urinary bladder where it is stored. If needed to maintain the animal's hydration, the urine is emptied from the bladder to the cloaca and retropulsed into the distal colon for reabsorption.

Clinical signs of renal disease in birds include polyuria, polydipsia, oliguria or anuria in acute disease, uric acid deposition in the case of articular or visceral gout, and hind limb paresis or paralysis if nephromegaly occurs. In general, birds with renal disease are systemically “ill”. These birds are lethargic, fluffed, anorexic, and dehydrated. Diagnosis of renal disease in birds is multi-modal and includes hematology, urine analysis, radiography, culture, and endoscopy. Clinical signs of renal disease in reptiles are often less pronounced and may include a gradual decline in appetite, activity, and body condition. Generalized edema can be apparent but is not specific to renal disease.

The cloaca of birds and reptiles serves as the common collecting chamber for urinary and fecal outflow. Fecal contamination of urine is unavoidable but urine can be evaluated if collected from the droppings in a timely manner if a non-absorbable substrate such as wax paper is used. Specific gravity in avian urine is usually between 1.005-1.020 g/µl and pH is 6.5-8.0. Polyuria due to renal disease or stress will most often be isosthenuric. Polyuria secondary to hepatic disease or primary polydipsia will usually be hyposthenuric. Very little protein should be in the urine as protein is excreted as urates in the droppings. Healthy birds will have little to no glucose in the urine. The presence of hematuria may indicate primary kidney disease or cloacal lesions. Ketones, bilirubin, and urobilinogen are not expected. Amorphous urate crystals are a common finding in avian and reptilian urine. Hemoglobin-like, granular, cellular and hyaline casts have been seen and are highly significant as a clear indication of renal inflammation or disease. Hematological evaluation should include a complete chemistry profile and complete blood count. An elevation in uric acid may be seen with renal disease but is not always present. Additionally, uric acid level can rise for other, unrelated, causes such as digestion of a high protein meal, muscle catabolism, and dehydration. Uric acid is actively eliminated through the kidneys by tubular excretion and is relatively unaffected by glomerular filtration rate in birds. Parameters such as calcium and phosphorus, in conjunction with uric acid and clinical signs, will help the practitioner interpret the relevance of these values. Radiography of the coelom will allow for visualization of the kidneys in some species, especially if nephromegally is present. Unilateral disease may indicate the presence of neoplasia. An excretory urogram is needed to visualize the ureters.

Treatment of renal disease in birds and reptiles often requires critical care and hospitalization. One goal of therapy is to decrease the uric acid level in the body by decreasing its production and enhancing its elimination from the body. Fluid therapy will have little effect on the plasma uric acid level but will provide systemic support to the critical patient and maintain perfusion. Since uric acid is the insoluable by-product of protein catabolism, diets low in protein should be fed to birds and reptiles with renal disease. Phosphorus binding products are useful additives to avoid absorption of dietary phosphorus which may exacerbate an existing hyperphosphatemia. Sodium restricted diets are not indicated for the management of renal failure in these patients as sodium may increase the solubility of uric acid. Allopurinol has been used effectively to inhibit uric acid formation. Colchicine/probenicid combinations are also helpful in removing uric acid from the body. Renal disease caused by bacterial nephritis is common either from ascending infections from the cloaca to the kidneys or hematogenous spread. Antibiotic therapy is indicated in these cases but antibiotic choice should be judicious. Avoid the use of sulfa drugs as these are excreted by the same pathway as uric acid and avoid nephrotoxic drugs such as the aminoglycosides. Renal failure often results in uric acid deposition in tissues. Articular gout occurs in chronic renal failure when uric acid tophi are deposited within the articular surface of joints. The resulting arthritis is extremely painful, thus analgesia is indicated and euthanasia should be considered when pain cannot be controlled. Visceral gout, the deposition of uric acid in the viscera, often occurs rapidly in acute renal failure. This condition may be suspected based on radiographic findings but it is often difficult to diagnose and treat.

Resources

Avian Medicine and Surgery. Altman R.B., Clubb S.L., Dorrestein G.M., Quesenberry K., eds. 1997. W.B. Saunders Co., Philadelphia, PA.

Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery, 2nd ed. Quesenberry K.E. and Carpenter J.W., eds. 2004. W.B. Saunders, St. Louis, MO.

Manual of Exotic Pet Practice. Mitchell M.A. and Tully T. N. 2009. Saunders, St. Louis, MO.

Reptile Medicine and Surgery, 2nd ed. Mader D.R., ed. 2006. Elsevier, Philadelphia, PA.

Textbook of Rabbit Medicine. Harcourt-Brown F. 2002. Butterworth-Heinemann, Oxford.

Veterinary Clinics of North America; Exotic Animal Practice – Renal Disease. Echols M.S., ed. 2006. W.B. Saunders Co., Philadelphia, PA.