Abstract
Most clinical information on the diagnosis and treatment of renal failure in reptiles has been reported from exotic pet medicine, primarily in the green iguana (Iguana iguana). This review of current diagnostic and treatment techniques is intended for new clinicians or veterinarians with more limited reptile experience. Antemortem diagnosis of renal disease is difficult. Hematologic changes are not consistent, although increases in phosphorus and uric acid, and decreases in total calcium have been reported in the green iguana. Inversion of the calcium:phosphorus ratio may be the first change noted. Even mild uric acid level elevations are concerning. Additional diagnostic options include urinalysis, radiographs, ultrasound, and biopsy. Treatment should focus on optimizing husbandry, fluid administration, provision of nutritional support, and treatment of coexisting disease. Allopurinol may help reduce uric acid levels.
Introduction
Renal disease categories are poorly defined in reptiles and the relationships between disease location (glomeruli/tubules), clinical signs, and laboratory values are not clearly established. Species variation in disease susceptibility, clinical presentation, and diagnostic changes are not defined. The etiology, diagnosis, and treatment of renal failure are best described in pet reptiles, primarily the green iguana and some tortoise species. Green iguanas develop at least one form of renal failure with consistent hematologic changes: decreased to normal total calcium (TCa), significantly increased phosphorus (P), and increased uric acid (UA).3 It is unknown if this syndrome occurs in other species. The etiology of reptilian renal disease is multifactorial and includes inappropriate husbandry, poor nutrition (level or type of protein, low water consumption, incorrect vitamin levels), toxic injury (e.g., nephrotoxic drugs), bacterial or parasitic infection, neoplasia, and possibly senescence.
Clinical Signs and Physical Examination
Chronic renal failure (CRF) is more commonly identified than acute renal failure (ARF) in the green iguana.6,24 Animals with CRF often have a history of inadequate housing and appear unthrifty. Animals with ARF generally present with better husbandry and body condition. There may be history of toxin exposure, including drug administration. Anorexia or declining appetite and weakness are reported commonly. Polyuria and polydipsia are rare.24 On initial examination, dehydration is usually apparent, digit tremors or muscle fasciculation may be present, and enlarged kidneys may be palpable. Evidence of pain and reluctance to move may be seen if gout deposits are present. Chronic renal failure may present as an acute collapse.
Diagnostics
The white blood cell count is frequently elevated.1-3,7 Mild leukocytosis with monocytosis or heterophilia is most frequently described.3,7 However, more severe increases are expected if infection or severe inflammation is present.7 Hematocrit (Hct) may be increased due to dehydration. A nonregenerative anemia has been reported with CRF.7
Total calcium levels are variable. In green iguanas, normal or decreased levels are described more commonly than increased values.7,24 A mean value of 7.8 mg/dl (1.95 mmol/L) was reported in a case series of 12 green iguanas.3 Total calcium is not always decreased and renal failure should still be considered if calcium levels are normal or high.15 In our collection, calcium levels are frequently elevated across a range of species in both sexes. Ionized calcium (iCa) levels are not commonly reported but may be helpful in evaluating animals. In mammals, CRF animals with normal or high TCa may have low iCa.22 Regular monitoring of iCa in normal and ill reptiles will allow for better definition of the usefulness of this test, such as in assessing the relationship between calcium levels and tremors.
Phosphorus is typically elevated, often significantly. In the case series noted above, average P levels were 23.8 mg/dl (7.7 mmol/L),3 though not all animals show hyperphosphatemia16. In the green iguana, hemolysis artificially increased phosphorus levels, so it is important to assess sample quality.16 Inversion of the TCa:P ratio may be the first sign of renal disease in green iguanas.7 Significant increases in P may be more consistent with renal failure than metabolic bone disease and elevations should prompt additional diagnostics.16
Metastatic mineralization is thought to occur from excessively high Ca and/or P levels which lead to deposition of mineral in soft tissues. In mammals, the solubility index (product of TCa [mg/dl] and P [mg/dl]) is utilized to evaluate the risk of deposition. An index >70 is associated with deposits in healthy tissue, an index between 50–70 is associated with deposits in abnormal tissue, and an index <50 is not associated with mineral deposits.8 Some clinicians advocate attempting to prevent the index from rising above 50 in reptiles.7 In our clinic, the index is often >70 at presentation (primarily due to elevated Ca levels). We have seen cases of abnormal mineralization but correlation with solubility index is not clear.
Uric acid values may increase with renal failure. Uric acid is secreted by the tubules and this rate appears unrelated to glomerular filtration rate.11,16 Values over 7 mg/dl (416 µmol/L) are of concern in iguanas.1 Values greater than this may be significant in herbivorous reptiles unless previous studies dictate otherwise. Reported ranges for herbivorous species show uric acid values less than 10 mg/dl (600 µmol/L).5,16,18,20 Uric acid is a breakdown product of protein metabolism and is normally increased after feeding. Carnivorous reptiles have elevations after a meal and repetition of testing is advisable. One author states that snakes should be retested 12 days after a meal.23 Hyperuricemia can lead to gout, the deposition of uric acid crystals in tissue. The UA level at which gout deposition occurs is not known for all species, but values over 24.7 mg/dl (470 µmol/L) are likely significant.6
Blood urea nitrogen (BUN) does not reflect renal function in reptiles but may increase with dehydration or catabolism.4,5,21 BUN levels are higher in carnivorous chelonians (up to 75 mg/dl/ 27 mmol/L) than in herbivorous reptiles.21 Elevations of BUN should prompt evaluation for improper husbandry and causes of dehydration or anorexia, including renal failure. Other hematologic changes include increased aspartate aminotransferase, alanine aminotransferase, and creatine kinase.1,3,24 Total protein and electrolytes may increase with dehydration.19
Urinalysis can provide helpful information about overall hydration and urinary tract health.9 Bladder urine does not reflect renal function as it does in mammals and urine specific gravity (USG), in particular, should be interpreted differently.7,9,12,15,19 A low USG is consistent with normal hydration, whereas elevated USG is abnormal. Urine specific gravities over 1.0059 and 1.01412 were considered abnormal in two chelonian studies. Renal disease in tortoises was associated with urine acidification, glucosuria, renal casts, and increased cell and bacterial counts.12 Uric acid crystals may be seen with gout. Bladder urine is contaminated by passage through the cloaca, but a pure culture of one organism should be considered significant.6,15
Diagnostic imaging can help diagnosis and highlight other problems, such as urinary calculi. Radiographs may demonstrate increased renal size and mineralization of soft tissues (especially great vessels) which have been associated with renal failure.3,6 Intravenous contrast studies have been described to help define renal size and function.6,14 Ultrasound should be utilized to assess renal parenchyma and allow evaluation of size, structural abnormalities, and mineral deposits.1,19
Kidney biopsy allows for definitive diagnosis and is commonly utilized in pet medicine. Various techniques are described; transcutaneous, major celiotomy, endoscopy and caudal keyhole.1,6,24 Surgical approach will vary with operator experience, kidney changes, species anatomy, and stability of the animal. Biopsy may not lead to a change of treatment plan, but allows confirmation of disease and may influence prognosis. Multiple biopsies should be submitted.19
Tests for early detection of renal disease do not exist but new techniques show promise. Research into nuclear scintigraphy to assess functional kidney mass in normal green iguanas indicated that uptake can be measured.10 The authors also explored bone density measurements with dual energy X-ray absorptiometry (DEXA) and expanded blood profiles for the diagnosis of renal secondary hyperparathyroidism.10 These techniques may prove useful in the future. Magnetic resonance imaging (MRI) would be useful to assess size and structure of the renal parenchyma.
Treatment and Management
The prognosis for reptiles with renal disease is grave but treatment and management of disease can be rewarding. One author reports 1-yr survival rates of 64% with acute renal failure and 22% with chronic renal failure in lizards.6 Husbandry changes are vitally important. Appropriate humidity and temperature are needed during hospitalization and long-term management. Regular monitoring of weight and blood values (Hct, TS, Ca, P, UA) is helpful for monitoring progress.6,17 A description of therapeutic planning and monitoring in treating dehydrated posthibernation tortoises is available17 and the same principles apply to treating renal failure.
Fluid support is the mainstay of therapy. Appropriate initial rates as high as 40 ml/kg/day have been advocated,6 though lower rates (25 ml/kg/day) may be equally beneficial19. Fluids can be given via many routes but intravenous (IV) or intraosseous (IO) routes are advocated in severe cases.6,17,19,24 The ideal fluid for treating renal failure has not been established and lactated Ringer’s solution,19 0.18% saline + 4% dextrose,6 and ½ LRS + 2.5% dextrose have been used.
It is important to monitor for overhydration (edema, respiratory difficulty), especially at high rates of administration. A gradual decrease in fluid administration should be initiated if the animal responds to treatment as judged by resumed urine production, improved hematologic values, and clinical improvement.6 As in small animal medicine, oliguric animals with acute renal failure can be treated with dextrose 20% IO or IV at 0.4–1 ml/kg/h for 30–60 min, then decreased to 0.2–0.5 ml/kg/h and furosemide in an attempt to re-establish renal flow.6 Intracoelomic dialysis has been described but is less effective than in mammals.6
Allopurinol may be used to treat hyperuricemia. It is a xanthine inhibitor that decreases uric acid production by stopping the full breakdown of purine. It appeared to be effective in reducing hyperuricemia and gout deposition in tortoises when dosed orally at 50 mg/kg every 72 h and was not associated with side effects over months of therapy.13 A dose of 20 mg/kg/day for 3 mo was used for posthibernation hyperuricemia.17 A dose of 20 mg/kg/day was reported to be beneficial in lizards with hyperuricemia secondary to renal failure.6
Phosphate binders may be utilized to help decrease phosphorus levels. Binders must be given with each meal to be effective. There is some concern that aluminum binders may lead to aluminum toxicity. Calcium carbonate acts as a phosphate binder and may be ideal for maintenance therapy.
Calcium supplementation may be needed either acutely or long term. Animals with twitching may have hypocalcemia and benefit from calcium gluconate IV or IO The treatment of animals with mild decreases in Ca and no clinical signs of hypocalcemia may be unnecessary.6 Some authors monitor the solubility index and only supplement Ca when P levels are decreased, thus keeping the solubility index low.6 Oral calcium supplementation may be used for maintenance. Adequate vitamin D3 levels may be maintained through the use of ultraviolet light or sunlight without direct supplementation. Vitamin D3 should help maintain calcium levels.6
Pain medications may also be useful, particularly if gout is present. Dietary support is important in the management of animals in the initial phases of treatment. Appropriate water intake and foods are important for long-term care. Dehydration should be corrected prior to loading the gastrointestinal tract.17 Syringe feeding, orogastric tube feeding, and pharyngostomy or esophagostomy tubes may be utilized in anorexic animals. There are no well-defined foods or feeding rates for reptiles with renal failure. The best option currently available is to place the animal on an appropriate diet and provide high levels of hydration. Herbivorous animals should not be given insect or animal protein. Carnivorous lizards may benefit by a change to alternate meat sources (whole minced chicken, white fish, Hill’s u/d).6 An informative discussion regarding diets in renal failure reptiles and the role of diet in causing renal failure is available.24
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