Correlation Between Plasma Uric Acid Levels and Histologic Renal Changes in Select Species of Reptiles
Abstract
The accuracy of uric acid levels in the diagnosis of specific renal diseases in reptiles has not been fully explored. This paper will review histologic renal changes of emerald tree boa (Corallus caninus), green tree python (Chondrophyton viridis), Asian water dragon (Physignathus cocincinus) and inland bearded dragon (Pogona vitticeps) and correlate them with antemortem plasma uric acid levels from blood taken within 3 days prior to death.
Introduction
Kidney disease is a common problem in reptiles.1 The etiology of renal disease is multifactorial and includes inappropriate husbandry, poor nutrition, toxic injury, bacterial and parasitic infection, neoplasia, and possibly senescence. Antemortem diagnosis is difficult3 because the symptoms may be mild and nonspecific, including anorexia, lethargy, and dehydration.1 Also, the hematologic changes are not consistent, although increases in uric acid and phosphorus and decreases in total calcium have been reported in iguanas3 and hyperuricemia has been associated with severe renal disease and gout in several species of reptiles2.
Uric acid is the primary catabolic end-product of protein, nonprotein nitrogen, and purines in reptiles.2 Of the total nitrogen excreted, 80 to 90% is in the form of uric acid in terrestrial reptiles.2 Plasma uric acid does not appear to be a sensitive test for renal disease in reptiles and elevations above normal values most likely require loss of two-thirds of the functional renal mass. Also, plasma uric acid is not a specific test for renal disease.2 Urinalysis is not a validated tool for use in the diagnosis of renal disease in reptiles.1 Renal disease categories are poorly defined in reptiles and the relationships between histologic changes, clinical signs, and laboratory values are not clearly established.
Methods
Animals chosen for this retrospective study had both histologic renal changes at the time of death and bloodwork taken within 3 days prior to death. Reptiles at the National Zoological Park (NZP) that filled these criteria included two emerald tree boas (Corallus caninus), two green tree pythons (Chondrophyton viridis), two Asian water dragons (Physignathus cocincinus) and two inland bearded dragons (Pogona vitticeps). Blood was obtained during clinical diagnosis of various renal and non-renal diseases and the reference range utilized for uric acid was that previously established in the Clinical Pathology Laboratory in the Department of Pathology of NZP. Histologic sections of kidneys were all stained with hematoxylin and eosin and changes within the glomeruli and tubules were evaluated for extent and severity.
Results and Discussion
The reference range for plasma uric acid at the National Zoological Park for the studied species are as follows: 5.2–12.2 mg/dl for green tree python, 12.8–12.8 mg/dl for Asian water dragon and 1.5–1.5 mg/dl for inland bearded dragon. No reference range has been established for emerald tree boas at the NZP clinical pathology laboratory.
As is shown in Table 1, both emerald tree boas had uric acid levels within assumed normal limits but both had moderate, acute and subacute changes in the glomeruli, tubules and interstitium. The green tree python that died due to renal failure (GTP1) had normal plasma uric acid values in bloodwork taken the day of death. Green tree python number 2 had very high levels, but only moderate glomerulosclerosis.
Both Asian water dragons had uric acid levels within normal limits, but both had a moderate amount of renal changes within the glomeruli, tubules and interstitium, including renal adenocarcinoma. Among the inland bearded dragons, animal number 1 had high uric acid levels but mild tubular degeneration. Inland bearded dragon 2 had intact renal tubules, mild glomerulosclerosis, and normal uric acid levels.
Table 1. Light microscopic changes in selected reptiles with uric acid levels determined within 3 days antemortem
Species
|
Animal number
|
Uric acid level (mg/dl)
|
Light microscopic findings
|
Emerald tree boa
|
ETB1
|
3.7
|
Mild glomerulosclerosis, moderate gouty tophi, mild tubular pigmentation, mild tubular dilation, moderate interstitial lymphoplasmacytic inflammation, moderate interstitial edema
|
Emerald tree boa
|
ETB2
|
4.7
|
Mild glomerulosclerosis, moderate tubular pigmentation, mucinous interstitial change, mild lymphoplasmacytic inflammation and leukemia
|
Green tree python
|
GTP1
|
3.5
|
Moderate glomerulosclerosis, moderate tubular pigmentation, moderate interstitial pigmentation, moderate interstitial edema
|
Green tree python
|
GTP2
|
72.5
|
Moderate glomerulosclerosis
|
Asian water dragon
|
AWD1
|
6.3
|
Moderate glomerulosclerosis, mild tubular mineralization, moderate tubular pigmentation, moderate interstitial pigmentation, interstitial fibrosis and mild lymphocytic and heterophilic interstitial inflammation and renal adenocarcinoma
|
Asian water dragon
|
AWD2
|
8.3
|
Moderate glomerulosclerosis, mild tubular degeneration, mild tubular mineralization, gouty tophi, moderate tubular pigmentation, mild interstitial edema, fibrosis and heterophilic inflammation and multilocular cysts
|
Inland bearded dragon
|
IBD1
|
20.1
|
Mild tubular degeneration and moderate interstitial fibrosis and mild lymphoplasmacytic interstitial inflammation
|
Inland bearded dragon
|
IBD2
|
4.4
|
Mild glomerulosclerosis, moderate tubular pigmentation, moderate interstitial heterophilic and lymphocytic inflammation, moderate interstitial fibrosis and edema
|
Histologic renal changes in these eight reptiles were generally mild to moderate and did not correlate consistently with uric acid levels determined within 3 days of death. Additionally, the animal with the worst histologic renal changes (GTP1) had normal uric acid levels. This supports the thought that plasma uric acid is not a sensitive test for renal disease in reptiles as was already suggested by some authors.2 Results of this study indicate that antemortem diagnosis of renal disease based on uric acid levels alone is not possible in reptiles. Conversely, normal levels of uric acid should not rule out renal disease, especially in green tree pythons.
Blood urea nitrogen values are also unhelpful in the diagnosis of renal disease because reptiles are primarily uricotelic. Additionally, creatinine is generally very low in reptiles and is only elevated in severe cases of dehydration and/or renal disease.2
Urinalysis is considered by some authors to be an unhelpful tool in the diagnosis of renal failure in reptiles.2 Urates may move retrograde from the cloaca into the colon and small intestine. It is possible, though not thoroughly studied, that fermentation or resorption of components of the urine may occur in the intestinal tract, altering the composition of the excreted product.4
In conclusion, uric acid levels alone are a poor indicator of renal disease in reptiles. The evaluation of renal function in snakes and lizards should employ a full chemistry panel and assessment of clinical signs, with renal biopsy as the most valuable ancillary diagnostic tool.
Literature Cited
1. Barten, S.L. 1993. The medical care of iguanas and other common pet lizards. Vet. Clin. N. Am. Sm. Anim. Pract. 1213–1250.
2. Campbell, T.W. 1996. Clinical pathology. In: Mader, D. (ed): Reptile Medicine and Surgery. Pp. 248–257.
3. Clayton, L.A. 2002. Renal failure and the reptile: a summary of diagnostic and treatment options. Proc. Am. Assoc. Zoo Vet. Annu. Meet. Pp. 291–295.
4. Singer, M.A. 2003. Do mammals, birds, reptiles and fish have similar nitrogen conserving systems? Comp. Biochem. Physiol. Part B. 134:543–558.