Renal disease in birds (Proceedings)

Renal disease in avian species is a relatively common occurrence in clinical practice and can be caused by a number of disease processes. Just as in other metabolic diseases (i.e. liver disease) determining a definitive diagnosis in a timely manner and administering appropriate therapy is crucial to the patient's survival. Unfortunately, kidney diseases in birds often carry a poor prognosis as many cases are diagnosed after they become chronic disease. This article will discuss methods of recognizing and diagnosing clinical renal disease in avian species including clinical signs, laboratory testing, diagnostic imaging, biopsy, histopathology and culture.

Clinical Signs

Clinical signs associated with kidney disease are highly variable and may be attributable to any number of disease processes. Clinical signs may include lethargy, depression, polyuria, polydipsia, dehydration, weakness, ataxia, lameness, weight loss, diarrhea and neurologic signs.

Complete Blood Count (CBC) and Biochemical analysis

Hematological data (CBC) allows the clinician to screen the hematopoietic system for abnormalities indicative of disease. However, biochemical assays are often more valuable when attempting to diagnose renal disease/failure in birds. The clinician should remember that consistently repeatable abnormalities in the biochemical panel are more diagnostic than a single value outside of reference ranges.

Serum and Plasma proteins and dysproteinemias

Changes in plasma protein levels, in particular hypoproteinemias, have been associated with renal disease; however, few studies have evaluated serum protein levels in avian species with confirmed renal disease.1

Phosphorous

Elevations in phosphate levels are commonly seen in mammalian species with renal disease. In avian species alterations (increase) in phosphorous levels do not occur consistently with renal disease and are of little diagnostic value.2

Urea Nitrogen

Unlike mammals, urea nitrogen (UN) occurs in only small amounts in avian plasma, is excreted by glomerular filtration (100%), and is not a particularly useful indicator of renal function in birds.2 However, there is some indication that urea is significantly affected by the patient's hydration status as it is 99% reabsorbed in the tubules during periods of dehydration and may be the single most useful indicator of prerenal (dehydration) causes of kidney disease in birds.1,3

Uric Acid

Uric acid (UA) is the major end product of protein breakdown in birds. It is produced and secreted in the liver, kidney and pancreas and eliminated by tubular secretion independent of glomerular filtration, water resorption and urine flow rate.1,3 Plasma uric acid levels are not highly dependent upon the patient's hydration status and reflect the functional capacity of the renal proximal tubules.4 Therefore, hyperuricemia may be an indicator of renal disease in avian species. Unfortunately, consistent hyperuricemia is most often seen late in renal disease thus somewhat limiting the diagnostic value of this test.2 Additionally, normal uric acid levels do not necessarily guarantee that the kidneys are healthy.2,5 Other factors may also affect uric acid levels such as age (juvenile birds may have lower UA levels than adults), diet (granivorous birds have 50% lower UA concentrations than carnivorous species), post-prandial increases in uric acid (carnivorous species), hyperuricemia associated with ovulation, and the presence of purine precursors from degraded body proteins.2.6-8 Hyperuricemia may also be associated with disease conditions such as articular gout (UA plasma levels may not always rise in association with visceral gout), severe tissue damage, starvation, hypovitaminosis-A induced damage to renal epithelium, nephrotoxic drugs and hypervitaminosis D3 induced renal damage may result in elevated plasma uric acid levels.2,9-12 Plasma uric acid levels within the range of 10-20 mg/dl should always be reevaluated.5

Plasma Urea:Uric acid ratios may be used to define pre-and post-renal azotemia because reabsorption of urea is disproportionally higher than uric acid, and therefore, this ratio should be high during dehydration and ureteral obstruction.13 Urea:uric acid = Urea [mmol/L] ×1000/Uric acid [μmol/L]

Creatinine

Creatinine is of questionable value in evaluating renal function in avian species because birds reportedly excrete creatine before its conversion to creatinine.13,14 Elevations in creatinine have been associated dehydration (pigeons) renal trauma or nephrotoxic drugs.13

Electrolytes

As in mammals, plasma or serum electrolyte levels should be evaluated with the understanding of the patient's appetite and thirst, hydration status, previous or current therapy and pathologic processes (i.e. gastrointestinal or renal disease) which may alter electrolyte concentrations. However, the significance of changes electrolytes and their association with renal disease requires more investigation in avian species.

Urinalysis

A urinalysis should be performed in birds with clinical evidence of renal disease including alterations in the biochemical panel (elevated uric acid). However, evaluation of avian urine samples may be complicated by both physiologic and anatomical issues in birds. First, the volume of urine found in the droppings may differ significantly between species. Secondly, urine is expelled from the cloaca and is often mixed with feces (with the exception of the ostrich). And lastly, ureteral urine may be refluxed into the lower gastrointestinal tract to the ceca (if present) where water and electrolyte reabsorption may occur further complicating its evaluation.15 This is especially true if concurrent disease processes within the gastrointestinal tract are present. Urine is collected from a clean, nonabsorbent surface (wax paper) from fresh dropping through the use of capillary tubes, syringes or pipettes.16 A standard dipstick for evaluation of mammalian urine can be used for avian species. The normal specific gravity for avian urines is 1.005-1.020 g/mL.17 The normal pH range for companion avian species is reported to be 6.5-8.0.16 Protein and glucose should only be present in trace amounts while ketones, bilirubin and urobilinogen should not be present in normal avian urine samples.16 Analysis of urine sediment is performed similarly to that of a mammal. Granular, cellular and hyaline casts may appear in avian urine sediment, but they are not always seen in birds with confirmed renal disease.

Diagnostic Imaging

Radiographs may be helpful in assessing kidney disease. The lateral radiograph is the most useful view to assess the size and shape of the avian kidney. Loss of the dorsal diverticulum of the abdominal air sac dorsal to the kidney may indicate renomegaly.4,18 One or more oblique view may be required to differentiate enlargement of the right or left kidney. Evaluation of the renal parenchyma via ultrasound may be complicated by the presence of the surrounding air sacs and synsacrum.14

Endoscopic Biopsy

Kidney biopsy during endoscopic examination of the coelomic cavity is indicated when the history, clinical signs and laboratory diagnostics (consistently elevated uric acid, polyuria, etc) support the presence of kidney disease. In fact, biopsy and histopathologic evaluation of the kidney parenchyma is the only way to accurately and definitively determine the cause of renal disease and to provide a reasonable prognosis for successful resolution of the patient's kidney disease.

Renal Scintigraphy

Marshall et al (2003) developed a standardized technique for performing renal scintigraphy in birds. In this study scintigraphy was used to assess gentamicin induced nephrotoxicosis in birds, to compare nuclear medicine assessments with histologic assessment of gentamicin nephrotoxicosis and serum uric acid concentrations, and to determine the radiopharmaceutical that best quantifies avian renal function.19 Marshall et al concluded that renal nuclear scintigraphy is a useful, noninvasive means to assess renal function in birds and Tc-DTPA is the radiopharmaceutical agent of choice.19

Blood Culture

Blood culture may be extremely useful in assessing patients with a suspected systemic bacterial disease causing renal disease/failure. Blood samples are collected from the jugular, basilic or medial metatarsal veins using strict aseptic technique and placed in appropriate blood culture media.

Treatment of Renal disease

Treatment of kidney disease is often multifactorial involving medical, nutritional and surgical management. If a definitive diagnosis is known then specific therapy should be aimed at resolution of clinical illness with appropriate therapy. Antibiotics, fluid therapy, nutritional support and metabolic support are paramount to helping the patient recover from insult(s) to the kidney.

Fluid Therapy

Fluid therapy to improve/maintain hydration status or induce diuresis should be instituted quickly in patients with renal disease. Warmed balanced electrolyte solutions should be given at a rate of 50 ml/kg per day either by oral, IV, intraosseous or subcutaneous routes (only in mildly dehydrated patients). It has been recommended to give 10% of the bird's body weight in fluids on a daily basis when the patient is in renal failure.1 Anuric and oliguric patient's should be diuresed with furosemide (0.1-2.0 mg/kg PO, SC, IM or IV q 6-24 hours) or mannitol (0.25-2.0 mg/kg IV slowly q 24 hours).20 In these patients remember that fluid intake should be restricted to fluid loss in these patients to prevent over hydration.1

Antibiotic Therapy

Antibiotic therapy is indicated in patients with suspected or confirmed bacterial nephropathies and are chosen based upon the culture and sensitivity reports or suspected bacterial organism, ease and frequency of administration and potential untoward effects (i.e. potential for nephrotoxicity). Antibiotics use by the author include: Trimethoprim sulfamethoxazole (30 mg/kg PO q 12 hours), Enrofloxacin (15 mg/kg PO, SC, IM q 12-24 hours), Ciprofloxacin (15-20 mg/kg PO, IM q 12 hours), Ceftiofur (100 mg/kg IM q 8 hours) and ceftazidime (50-100 mg/kg IM q 6-12 hours).13,20

Other Medications

The use of allopurinol to treat hyperuricemia remains controversial. Allopurinol acts to reduce uric acid production by inhibiting xanthine oxidase. Allopurinol was shown to be toxic and induced hyperuricemia and gout in red-tailed hawks (Buteo jamaicensis) when given at a dose of 50 mg/kg PO q 24 hours.1,13 However, no significant effect on plasma uric acid levels were determined in subjects given allopurinol at a dose of 25 mg/kg PO q 24 hours.1 Colchicine, which acts to reversibly inhibit xanthine dehydrogenase, may be used to no only reduce plasma uric acid levels but also to treat renal fibrosis and is well tolerated when given in conjunction with allopurinol.13 Urate oxidase has been suggested as an alternative method to managing hyperuricemia in avian species.1,13 Urate oxidase is reported to degrade excess uric acid to allantoin which may be further broken down to allantoic acid and excreted by the kidneys.1 Urate oxidase given to pigeons (200 and 600U/kg) and red-tailed hawks (100 and 200 U/kg) resulted in a significant decrease in plasma uric acid concentration within 2 days of the first dose.20 The study concluded that urate oxidase is much more effective compared with allopurinol, but further investigation is necessary.

Nutritional and Dietary Management

Appropriate supportive (dietary) care should always be given to patient suffering from renal disease. Patients should be fed a well-balanced diet appropriate for their respective species. Protein restricted diets should be used judiciously.

Nutritional Supplements, specifically omega(ω)-3 fatty acids, have been used to manage renal disease given their anti-inflammatory, lipid stabilizing and antinoeoplastic effects and renal protective properties however, there are no reports of their controlled use in avian patients. Echols (2006) suggest a dose of 0.22 ml/kg of product containing <6:1 ω-6: ω-3 fatty acids.13 Hypovitaminosis A has been reported as a cause of renal disease in avian species and results in metaplasia of the ureters leading to hyperkeratinization, decreased mucin production and impaction.22,23 Parenteral Vitamin A (2000-5000 IU/kg once) in conjunction with dietary modification may prove to be therapeutic. The dose of Vitamin A should be repeated in 3 weeks if indicated.13

Surgery

Surgical intervention to treat renal disease in birds is relatively unrewarding owing to the anatomical position of the kidneys and the vascular supply of the kidneys. Post renal disease/failure due to urolithiasis, ureteroliths or cloacoliths may respond well to surgical correction.13

References provided on request