禽类肾病的诊断和治疗

Diagnosis and Treatment of Avian Renal Disease Christal Pollock, DVM, DABVP-Avian College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66502, USA Significant causes of renal disease in the companion parrot include de- hydration, hypovitaminosis A, excessive dietary vitamin D3, heavy metal toxicity, bacterial nephritis secondary to systemic disease, and renal carci- noma. Additional important differentials include renal lipidosis in merlins and amyloidosis in waterfowl and songbirds. Diagnosis of renal disease may rely on the identification of consistent clinical signs, clinical patho- logy, survey radiographs, and laparoscopic evaluation and biopsy of the kidneys. Treatment of avian renal disease relies on supportive care such as fluid therapy and nutritional support. Other treatments vary with the underlying cause and the clinical picture but may include systemic antibi- otics, diuretics, parenteral vitamin A, and agents to lower uric acid levels such as allopurinol. Reports on the incidence of renal disease in the avian patient vary, but renal disease is common in poultry and birds of prey [1,2]. Clinical renal disease is probably under-recognized in the companion bird, with the notable exception of renal tumors in the budgerigar (Melop- sittacus undulatus). Clinical signs of renal disease Vague clinical signs such as weakness, anorexia, vomiting, or regurgita- tion often predominate in avian renal disease [3,4]. Early signs of mechan- ical compression or invasion of spinal nerves may include twitching and Vet Clin Exot Anim 9 (2006) 107–128 subtle signs of pain [3–8]. In rare instances, painful behavior may include feather picking or self-mutilation over the synsacrum [4,8,9]. As disease progresses, hematuria, unilateral or bilateral limb paresis, and disuse mus- cle atrophy may be observed [3,4,10,11]. Renomegaly may also lead to E-mail address: cpollock@vet.k-state.edu 1094-9194/06/$ - see front matter � 2006 Elsevier Inc. All rights reserved. doi:10.1016/j.cvex.2005.10.007 vetexotic.theclinics.com cloacal atony and constipation [4,7]. Metabolic abnormalities, particularly those caused by bacterial or viral nephritis, may cause persistent polydip- sia/polyuria and, less commonly, oliguria, anuria, or seizure activity [3,4,6,8]. Important differentials for primary renal disease Metabolic causes of renal disease Dehydration is an important contributor to renal disease. Severe or persistent dehydration increases resorption of water causing a subsequent reduction in urine flow. As uric acid secretion decreases, urates may precip- itate in renal tubules and ureters leading to impaction and potentially renal failure [2,12–15]. Deposition of lipid in renal tubules is an important problem of chicks, poults, and adult captive merlins (Falco columbarius) [16,17]. This condition has also been reported in the budgerigar parakeet and sulfur-crested cocka- too (Cacatua galerita) [7]. Renal lipidosis has been correlated with high-fat or low-protein diets, starvation, biotin deficiency, and chronic liver disease [2,15–17]. Poultry may exhibit acute onset of lethargy, followed by paralysis and death [16,17]. Merlins generally die acutely and are found in good flesh or slightly overweight [16]. Neoplasia of the avian kidney In a study of 1203 budgerigar parakeets, 16% had tumors, and 23% of these tumors were renal [11]. The most common tumor in the bird is renal adenocarcinoma, which sometimes causes osteolysis and sclerosis of the ileum and synsacrum and potentially infiltrates nearby muscle and other surrounding tissue [7,15]. Distant metastasis to the skin, lung, liver, and ovi- duct is rare [15,18–20]. Nutritional causes of renal disease Excess dietary protein or calcium, hypovitaminosis A, or hypervitamin- osis D may lead to nephritis and other degenerative renal changes [21]. Pro- found vitamin A deficiency causes squamous metaplasia of ureteral mucosa and collecting ducts leading to blockage of the ureters and secondary hydro- nephrosis, hyperuricemia, and oliguric/anuric renal failure [2,4]. Excess vitamin D3 promotes metastatic mineralization of viscera includ- ing the kidney [15,22,23]. This problem most commonly affects nestling par- rots [15]. Clinical signs may include polyuria/polydipsia, anorexia, crop 108 POLLOCK stasis, and weight loss [14,22]. The recommended level of vitamin D3 for chickens is 300 IU/kg feed. Toxic effects reportedly occur with vitamin D3 levels exceeding 1000 IU/kg feed [23]. Inflammatory causes of renal disease Renal amyloidosis is most common in captive, adult waterfowl, shore- birds, cranes, flamingos, and songbirds [4,15,24]. Amyloidosis is often asso- ciated with chronic inflammatory conditions such as sepsis, gout, enteritis, and arthritis [24–26]. Infectious causes of renal disease The absence of lymph nodes and the presence of renal and hepatic portal systems increase the risk of systemic or gastrointestinal microbes affecting the kidney [27,28]. Viral nephritis Avian polyomavirus is the most important cause of viral nephritis in the companion psittacine bird. Up to 70% of affected non-budgerigar psitta- cines develop glomerulopathy characterized by immune complex deposition, but affected birds die acutely from other problems without showing signs of renal disease [4,15,26,29–31]. Other viruses with tropism for the avian kidney include infectious bron- chitis virus, picornavirus, paramyxoviruses such as Newcastle disease virus, influenza virus, and togaviruses [12,15,27,32–34]. Infectious bronchitis virus is an important cause of renal disease and urolithiasis in galliforms [12,15,32]. Lymphoplasmacytic interstitial nephritis is common in birds in- fected with West Nile virus but only as a part of generalized disease [15,35]. Bacterial nephritis Bacterial nephritis usually occurs when bacteria enter the kidney second- ary to systemic disease through the renal arteries or the renal portal system [4,26]. Rarely, bacteria ascend the ureters secondary to conditions such as chronic cloacitis [4,23,26]. A wide range of bacteria has been reported to cause bacterial nephritis including Enterobacteriaceae, Pasteurella spp, Pseudomonas spp, Streptococcus spp, and Staphylococcus spp [4,15,26,27]. Listeria monocytogenes has been reported in raptors [15,26], whereas Erysi- pelothrix rhusiopathiae has been reported in quail and chicken [15,26,36]. Mycobacterium avium can, rarely, cause renal lesions [15,37]. Chlamydial nephritis Chlamydial nephritis is poorly documented [4,38]. In a survey of 23 birds with psittacosis, 35% had renal congestion, bile pigment nephrosis, and glo- 109DIAGNOSIS AND TREATMENT OF AVIAN RENAL DISEASE merulopathy, but Chlamydophila psittaci could not be detected in renal tis- sue [26]. Identification of chlamydial organisms in the avian kidney has been reported in only two juvenile parrots [38]. Fungal nephritis Fungi are a rare cause of renal disease [4,39]. Lesions may develop from fungal invasion of vessels or extension from air sacs [15]. Parasitic nephritis Renal coccidiosis is the most important cause of parasitic nephritis. Dis- ease caused by the coccidian Eimeria spp is most common in free-ranging, juvenile waterfowl [40,41]. Disease has also been described in the domestic goose (Anser anser domesticus) and aquatic birds such as the loon (Gavia im- mer), gull (Larus argentatus), puffin (Fratercula arctica), cormorant (Phala- crocorax auritus), woodcock (Scolopax minor), and penguin (Eudyptula minor) [14,15,42–45]. Renal coccidiosis is less commonly reported in raptors [15]. Although renal coccidiosis is often asymptomatic, emaciation, acute re- nal failure, and death may occur secondary to granulomatous interstitial ne- phritis [14,46,47]. The microsporidian, Encephalitozoon hellem, may also cause severe granulomatous nephritis [14,26,46,48–50], although the presence of micro- sporidians in the kidney or urine can be incidental [14,15,51]. Renal mi- crosporidiosis is most commonly reported in the lovebird (Agapornis spp), particularly those positive for psittacine beak and feather disease [50,51]. There are also reports of renal microsporidiosis in the budgerigar, eclec- tus (Eclectus roratus), and red-bellied parrot (Poicephalus rufiventris) [51,52]. Traumatic causes of avian renal disease In mammals, crush injuries and other conditions causing muscle necrosis are known to cause tubular changes, myoglobin cast formation, and renal failure, [14] Myogobinuria has been reported in flamingo (Phoenicopterus sp) and ostrich (Struthio camelus) with capture myopathy, and there is one report of renal failure in an ostrich with extensive muscle necrosis and marked hyperuricemia [14,27]. Direct trauma is rare because the avian kidneys are so well protected by bone [7]. If a renal hematoma does develop, it can apply pressure to spinal nerves causing limb paresis [27]. Crushing of the kidney may also occur dur- ing dystocia [46]. Toxic nephropathies in the avian patient 110 POLLOCK Because of the presence of renal and hepatic portal systems, the avian kidney is frequently affected by toxins in the avian gut such as heavy metals, anti-inflammatory agents, and antibiotics [28]. Lead toxicity is associated with acute tubular necrosis or nephrosis and visceral gout [53]. The nonsteroidal anti-inflammatory agent flunixin has been implicated in presumptive nephrotoxicity of cranes and flamingos [54]. In northern bob- white quail (Colinus virginianus), doses of flunixin as low as 0.1 mg/kg led to the development of gout [54]. Another nonsteroidal anti-inflammatory agent, diclofenac, has been linked to renal failure, visceral gout, and high death rates in vultures of the Indian subcontinent [55]. Most information regarding antibiotic nephrotoxicity is based on studies in mammals. For instance, renal tubules accumulate aminoglycoside poten- tially leading to nephrotoxicity in mammals [56]. Gentamicin may be more likely to cause nephrotoxicity in the bird because polyuria/polydipsia is of- ten seen even at low doses [56]. Gentamicin (5 mg/kg intramuscularly every 12 hours for 7 days) led to profound polyuria/polydipsia in cockatoos (Eolophus sp) which persisted for 23 days after stopping treatment [57]. Loss of balance, impaired vision, and muscle spasms were described in two fal- cons (Falco biarmicus) given gentamicin (5mg/kg/d for 4 days) [58]. Amikacin is considered the least nephrotoxic of the aminoglycosides, but transient polyuria/polydipsia may still occur [59]. A host of other drugs and toxins have been associated with renal lesions in birds, including dexamethasone, medroxyprogesterone, aflatoxins, myco- toxins, herbicides, and vitamin D3-based rodenticides [15,46,60,61]. There are also reports of oak toxicity in a cassowary (Casuarius casuarius) [62] and of ethylene glycol poisoning in geese [63]. Postrenal disease Conditions such as urolithiasis, dystocia, cloacal, or coelomic masses and, in rare instances, ureteral tumors may cause mechanical compression or obstruction of the avian ureter [7,64]. Urolithiasis and visceral gout Urolithiasis and visceral gout are important causes of renal failure in pul- lets and caged laying hens. These conditions are seen only sporadically in companion birds [2,28]. Visceral gout is defined as the accumulation of uric acid tophi on serosal surfaces of the pericardium, liver capsule, air sacs, and within the kidney but may be found any tissue [26]. Urolithiasis is simply the presence of urinary tract calculi. The pathogenesis of gout is not completely understood, but gout is gen- erally associated with conditions that reduce uric acid excretion or increase uric acid production [2,23,65]: Reduced uric acid excretion Increased uric acid production Dehydration 111DIAGNOSIS AND TREATMENT OF AVIAN RENAL DISEASE Excess dietary calcium Renal tubular disease Excess dietary protein Infectious renal disease Hypovitaminosis A Obstructive ureteral disease Urolith development is most commonly associated with severe dehydra- tion; other factors may include excess dietary calcium, dietary electrolyte im- balances, infectious bronchitis virus, Mycoplasma synoviae infection, mycotoxicosis, or shipping stress [12,13,66–68]. Excess dietary protein has also been correlated with increased production of uric acid, but even with very high levels of dietary protein (ie, 80%) gout develops only in genetically susceptible individuals [69,70]. Nevertheless, it is still theorized that long- term of high-protein feeding may induce hyperuricemia in granivorous or nectivorous birds [23,71]. The presence of uroliths in the kidney leads to compensatory hypertro- phy of remaining renal tissue. Affected birds often appear normal until ure- teral flow from the contralateral kidney is blocked, leading to lethargy, straining, and death [27,66,67]. Visceral gout is rarely diagnosed ante mor- tem, and birds are usually found dead [4]. Articular gout Articular gout is defined as the accumulation of uric acid tophi in or around joints. Articular gout lesions are particularly common on the foot and hock [65]. Clinical signs of articular gout may include reluctance to move, shifting from leg to leg, lameness, and joint swelling [4]. Diagnosis Early recognition and diagnosis of renal disease is extremely challenging, but an early definitive diagnosis provides the best opportunity for helping the patient [3]. Clinical pathology In advanced renal disease, normocytic-normochromic anemia, hyperuri- cemia, uremia, and changes in plasma electrolyte, calcium, and phosphorus levels may be detected [72]. Uric acid excretion is largely independent of urine flow and therefore is unaffected by moderate changes in glomerular fil- tration [72]. Elevations in uric acid (up to 20 mg/dL) may be seen with severe dehydration [23,73,74], but uric acid does not increase significantly with re- nal disease unless there is extensive tubular damage [75]. Postprandial hy- peruricemia may occur for up to 8 hours in carnivorous birds [76,77]. Urea nitrogen (BUN) has little value in the detection of renal disease in 112 POLLOCK most birds [4,73], but BUN is a sensitive indicator of hydration. In the de- hydrated bird, up to 99% of BUN is reabsorbed. A significant postprandial elevation in BUN has also been documented in healthy raptors [77]. The avian kidney cannot concentrate sodium or electrolytes much above normal levels [78]. Possible findings with renal failure may include hypo- natremia, hyperkalemia, hypocalcemia, and hyperphosphatemia [27], al- though elevations in phosphorus are not commonly recognized in avian renal disease [72,74]. Alterations in these electrolytes have been inconsis- tently reported in active cases of avian renal disease. No definitive correla- tions between electrolyte abnormalities and renal disease in birds have been made. Urinalysis Urine flows from the ureters into the urodeum and then enters the colon and, in some species, the cecum or ileum, by reverse peristalsis (Fig. 1) [79,80]. Columnar epithelial cells lining the urodeum and colon modify ure- teral urine through the absorption or secretion of water, electrolytes, and nitrogen [78]. Important indications for urinalysis include persistent biochemical or radiographic abnormalities consistent with renal disease or persistent polyuria (Fig. 2) [14]. Causes of polyuria are extensive and non- specific and include fluid therapy, renal disease, liver disease, gastrointesti- nal disease, diabetes mellitus, and pituitary tumors [4,14]. Polyuria may also occur with sepsis even when the pathogen does not directly affect the kidney, and psychogenic polydipsia has been reported in one African gray parrot (Psittacus erithacus) [14,81]. A common cause of polyuria and polla- kiuria in the avian patient is stress [14,82]. Fig. 1. Retroperistalsis of urereteral urine from cloaca (A) into avian large intestine (B, C, D). 113DIAGNOSIS AND TREATMENT OF AVIAN RENAL DISEASE (E) the femurs. (From Brummermann M, Braun EJ. Effect of salt and water balance on colonic motility of white leghorn roosters. Am J Physiol Regulatory Integrative Comp Physiol 1995;268:690–8; with permission.) Although cloacal cannulation techniques have been described [83], free- catch urine samples are always collected from clinical patients. Obtain fresh urine samples free of urates and feces from clean, nonabsorbent surfaces such as wax paper [3,14,23,46]. A free-catch urine sample does not necessar- ily represent ureteral urine, and this fact should be taken into account when interpreting the results. Birds possess a limited ability to concentrate urine, making avian urine isosmotic or slightly hyperosmotic. Urine specific gravity normally ranges from 1.005 to 1.020 g/mL but is highly variable among the different species. Urine specific gravity is not particularly useful unless values are consistently low [14,46]. Urine color Pigments present in feces or newspaper can leach into urine and urates over time [14,23]. In the anorectic bird, concentrated bile pigments create emerald green or black feces that may stain urine even before droppings are passed [23]. Liver dysfunction or, in rare instances, hemolysis, may lead to biliverdinuria or lime-green, yellow, or, less commonly, orange urine and urates [14,23,46]. Red urine may be seen with hematuria, hemoglobinuria, or myoglobinu- ria. Hemoglobinuria may be seen in Amazon parrots (Amazona spp) with lead toxicosis producing dark red, pink, or tan/brown urates [4,23]. Hema- turia may be associated with renal neoplasia, nephritis, or toxic nephropa- thy, although blood can also originate from the intestinal or reproductive Fig. 2. Polyuria in a bird dropping. Notice the large ring of urine around the feces and urates. (Courtesy of Ed Ramsay, DVM, DACZM.) 114 POLLOCK tracts [4,23]. Transient wine-colored urine may occur in chicks, especially African gray and eclectus parrots. This condition may be correlated with hand-feeding animal protein–based diets [4,14,23]. Urine dipstick parameters The pH of avian urine typically ranges from 6.0 to 8.0 [14,46,9]. Urine pH may be influenced by diet and cloacal contents [23,46], with urine more acidic in laying hens and more alkaline with bacterial metabolism [84]. Glu- cose levels in urine are normally zero to trace, although biliverdinuria may interfere with urine protein readings [23,46]. Normal avian urine is also free of ketones except during starvation or migration, when metabolism switches to beta-oxidation of fats [23,26]. Standard mammalian urine dipstick tests should be interpreted with caution, because these tests are not designed or calibrated for accuracy with avian species. Urine sediment Lane [46] recommends centrifugation of urine for 1 to 2 minutes. Normal sediment contains many squamous epithelial cells and amorphous urate, cal- cium oxalate, and sulfonamide crystals [46]. Low numbers of red and white cells (!3/high power field, � 40) are present in avian urine. There should also be small numbers of bacteria present that are probably from fecal or cloacal contamination [14,23,46]. Normal bird urine contains no casts. Granular, hemoglobin, and other casts are reported in the literature and may be associated with renal disease [14,46]. Blood culture To identify the cause of sepsis and bacterial nephritis, blood culture is a much better test than urine culture [14]. Radiographs The avian kidney is difficult to evaluate radiographically because of its po- sition within the synsacral fossa. Obscured by parenchyma on the ventrodor- sal view, the kidneys are best viewed on the lateral projection. The most consistent radiographic sign of renomegaly is enlargement of the cranial re- nal division, which is best appreciated on the lateral view. Enlargement of this cranial renal division will also make the kidneys more apparent on the ventrodorsal view [3,7]. Renomegaly will also cause the wedge of