Melissa Kaplan's
Herp Care Collection
Last updated January 1, 2014

Clinician's Approach to Renal Disease in Lizards

©1999 Stephen J. Divers, BSC, MiBiol, BVetMed, MRCVS, Proceedings of the ARAV, October 24-27, Sacramento CA

Abstract
Renal disease is a major cause of mortality in captive lizards. Captive husbandry and diet are the most common predisposing causes of chronic renal failure, typically seen in the adult lizard, while acute renal disease is often infectious or toxic in nature and appears to be more sporadic. Historical and clinical presentation can vary and the clinician must often rely on hematology and biochemistry, urine analysis, radiography, and biopsy for a definitive diagnosis. Diagnostic and treatment regimes are outlined.

Key words: renal failure, kidney disease, lizard, squamata, green iguana, radiography, urography, endoscopy, fluid therapy

Introduction
To appreciate and understand the problems of renal disease in lizards a few basic anatomical and physiological peculiarities must be understood [1, 3]. All lizards are essentially uricotelic, such that their main excretory product of protein metabolism are salts of uric acid (urates) which are produced by the liver. Uric acid is largely insoluble which serves to reduce insensible water losses associated with excretion but does predispose dehydrated lizards to gout if plasma uric acid levels rise above 1487 µmol/L [4, 5]. Uric acid is actively secreted via the proximal renal tubules. The squamate kidney is metanephric in structure, has relatively few nephrons, lacks a loop of Henle and lacks a renal pelvis. Therefore most reptiles are virtually unable to concentrate urine of a greater osmolarity than that of plasma. In addition, mature male lizards may possess sexual segment proliferation of the distal tubule. This is a pale pink glandular tissue designed for the production of seminal fluid. Grossly, the kidneys are dark brown in color, paired, short and broad with few lobes. They are located in the caudodorsal coelomic cavity or pelvis. In laterally flattened lizards (e.g., chameleons) the kidneys are located craniodorsal to the pelvis.

Urine produced by the kidneys flows down a ureter-like mesonephric duct to the urodeum of the cloaca, where it then passes into the bladder (if present) or cranially into the distal colon for storage prior to evacuation. Variable changes in urine concentration and electrolyte composition can occur within the bladder or distal colon. This means that bladder urine is not sterile and may not be a true osmotic/electrolyte representation of renal urine. A renal portal system is anatomically present but its functional significance is questionable. Nevertheless all potentially nephrotoxic or renally excreted drugs should be injected into the cranial part of the lizard.

Clinical Investigation

History and Clinical Findings
In cases of acute renal disease, there will usually be very little in the way of historical evidence. Essentially, the lizard becomes rapidly depressed, lethargic, anorexic and weak, often with a complete cessation of urate output. The use of nephrotoxic drugs (e.g., aminoglycosides) or exposure to poisons or toxins may be inferred from a decent history. Often these animals enjoy good nutrition and a reasonable level of husbandry. On physical examination, most acute cases will be of good weight and reasonable body condition. Dehydration may be evident due to reduced skin elasticity, and pharyngeal edema may be noticed. The kidneys may or may not be palpable.

In cases of chronic renal disease, there will often be nutritional (high protein diets, excess vitamin D3 supplementation) or husbandry factors (low humidity, mild long term water deprivation) that may indicate potential renal compromise. Such animals tend to have a history of reduced appetite poor, weight gain or weight loss, and occasionally owners may notice increased drinking. They are usually of poor body condition, dehydrated and the kidneys may or may not be palpable. Unfortunately, most owners miss the initial signs associated with kidney disease, and so chronic cases will often be presented as emergencies just like the true acute renal failure case.

A thorough physical examination is essential but it is often necessary to resort to laboratory techniques and ancillary diagnostics to make a definitive diagnosis.

Medical Stabilization
The aim must be to stabilize the patient prior to diagnostic work-up. Take a blood sample for laboratory investigation prior to initiating i.o. or i.v. fluid therapy at 20-40 ml/kg/d. The provision of a suitable thermal environment must never be overlooked.

Laboratory
A basic data base including complete blood count and basic biochemistry is essential in any reptile presenting with anorexia, depression and lethargy and will direct the clinician towards further laboratory tests and ancillary diagnostics (Table 1).

The calcium and phosphorus ratio is often a reliable indicator of renal disease, and is usually elevated before any other biochemical parameter. The solubility index is calculated as the product of Ca (mmol/L) x PO4 (mmol/L), and is normally less than 9. If the solubility index rises above 12 then healthy tissue will start to mineralize, while between 9 and 12 mineralization of diseased tissue (kidneys) occurs.

Urine samples, either freshly voided or obtained by cystocentesis, should be examined. Although lizard urine is not as clinically useful as mammalian urine, examination is warranted, particularly if obtained by cystocentesis. Microscopic examination may reveal blood, a high inflammatory cell presence or renal casts indicating active infection and acute disease. Normal bladder urine may not be sterile, but if a culture and sensitivity reveals a profuse growth of a single organism then that may be significant and worth acting upon.

Diagnostic Imaging and Endoscopy
Dorsoventral radiographs are useful in most lizards for assessing kidney size, especially if the kidneys are enlarged. Radiography will also demonstrate renal stones and/or soft tissue mineralization. In the laterally compressed lizards a horizontal beam lateral is more useful. It is important to look for bladder stones, changes in bone density and also constipation due to renal enlargement. lntravenous urography can be very usefuI when attempting to identify renal masses (abscess, neoplasia, calculi), renal and ureteral damage and ureteral obstructions. A cut-down procedure is made to catheterize a cephalic or jugular vein, although the author has had some success using an intraosseous line into the proximal tibia. Then 500 mg/kg of suitable water soluble iodine compound (Conray 280, 280 mg iodine/ml, May & Baker) is injected i.v. Or i.o. Radiographs are taken at 0, 5, 15, 30 and 60 min post injection.

Ultrasonography from the ventral mid line and just caudal to the vent can also be used to assess gross pathological changes.

There is increasing interest in the use of MRI (which is superior to CT scanning) but the limited availability and costs of such imaging techniques makes them practically obsolete for most clinicians.

The problems facing the clinician include making a definitive diagnosis, determining if it is acute or chronic, providing specific therapy and general support, and providing the owner with a prognosis. To this end the author has found that renal biopsy represents the most important diagnostic and prognostic tool when investigating renal disease.

Renal biopsies can be taken in four ways: major celiotomy approach, cranial tail cut-down approach, transcutaneous needle biopsy and endoscopic biopsy. The author prefers endoscopic biopsy because it enables visualization of both kidneys and ureters via a small laparoscopic (celiotomy) incision and the taking of 1-4 small biopsies (3 Fr) which are submitted for culture and histology. In the vast majority of cases biopsy provides the definitive diagnosis and helps give the owner a prognosis. The site of entry is in the paralumbar area, with the lizard in lateral recumbency; Air inflation aids visualization. The author's personal opinion is that as soon as the lizard is hydrated and stable for anesthesia, endoscopy and biopsy should be attempted.

Treatment
(See Table 2)

Acute renal failure (ARF):
The aim is to keep the lizard alive until sufficient healing has taken place. If reversed, the chance for a complete recovery does exist. Initially an accurate weight is essential as is an accurate assessment of hydration status based on packed cell volume (PCV) and plasma total protein. Rehydration using 0.18% saline + 4% glucose is recommended at 20-40 ml/kg/d i.v. Or i.o. Hartmann's solution may be less appropriate in cases of hyperkalemia (>8 mmol/L). The author assumes that there may be severe acidosis during acute renal failure. However, not having the laboratory equipment available to measure acid-base balance, the author prefers to ignore acid-base disturbances on the basis that if renal perfusion and function can be restored then the kidneys will correct the acidosis.

Hydration status should be monitored using serial weight and PCV measurements. When correct hydration has been achieved, it is vital that over hydration is avoided and therefore a reduction in maintenance fluids to 2-10 ml/kg/d is required but hydration status must continue to be monitored. If over hydration does occur (pharyngeal edema, pulmonary edema) then the use of diuretics is advisable (furosemide, thiazides).

In cases where uric acid levels are significantly elevated (>750 mmol/l) the use of allopurinol (20 mg/kg p.o. q 24 hr) may reduce hepatic uric acid production, while the administration of anabolic steroids may reduce protein catabolism. In cases of pre-renal ARF, rehydration, restoration of circulatory volume and supportive therapy may be all that is necessary. In cases of post renal obstruction, renal stones and ureteral obstructions will often have to be surgically removed before urine flow can be reestablished. In cases of toxin induced nephropathy, identification and removal of the toxin from the environment and gastric lavage may be useful. In cases of suspected aminoglycoside toxicity all drug medication should stop and osmotic diuresis instigated to maintain renal perfusion once normal hydration status has been achieved. Acute hypercalcemia (from acute vitamin D3 overdose but not breeding females) can cause ischemic acute tubular necrosis through the development of nephrocalcinosis, and in such cases prednisolone, calcitonin and diuresis should be considered. Chronic renal damage can also lead to calcium salt deposition in soft tissues including the kidney due to an elevation in the solubility index. Acute renal disease due to infectious agents should be empirically treated with broad spectrum anti microbials until culture and sensitivity results are obtained. It is important to use drugs with a large safety margin as drug metabolism and excretion may be significantly affected.

If the lizard remains oliguric once hydration and any underlying causes have been addressed, then the i.v. Or i.o. administration of 20% dextrose may be used in an attempt to induce diuresis. Initially dextrose is given at 0.4-1.0 mI/kg/hr i.v. Or i.o. for 30-60 min, then the rate is reduced to 0.2-0.5 MI/kg/hr. If the lizard remains oliguric, then diuretics and coelomic dialysis may be attempted. The right lateral coelomic region just cranial to the right limb is prepared aseptically and a 18-23 g 25-50 mm Teflon catheter is introduced into the coelomic cavity and sutured to the skin. Warm (30-35 C) fluids (30-40 ml/kg) are injected into the coelomic cavity and left in situ for 1-2 hr before being removed. Balanced electrolyte and hypertonic 5% dextrose solutions are recommended, however due the relative insolubility of uric acid compared to urea, dialysis appears to be less effective in reptiles than mammals.

(From January 1995 to January 1996, the author has treated 11 cases of acute renal failure in lizards, 7 cases (64%) are known to have survived for longer than a year.)

Chronic renal failure (CRF):
Unfortunately, most cases of CRF present as acute emergencies because the owners have missed the early signs of disease. Essentially, the aim of therapy is two fold. First, stabilize the patient in much the same way as for acute renal failure, diagnose the cause of the renal disease (neoplasia, abscessation, tubulonephrosis), and perform specific therapies including surgery to resolve any immediate crisis. Then, in the long term, instigate ongoing therapy to reduce further renal compromise. These long term measures include:

Reducing the protein intake of the diet. Herbivorous lizards should not be given any animal or insect protein. Carnivorous tegus and monitors should be offered less higher quality protein (e.g., whole minced chicken, whole minced white fish, Hill's a/d diet). Insectivorous lizards should be offered lower protein insects such as mealworms and earthworms, avoiding the higher protein locusts. lf however, weight loss ensues due to protein-losing nephropathy then an increase in dietary protein may be required. Long term allopurinol therapy may be used to reduce uric acid production.

Reducing hyperphosphatemia using phosphate binders (aluminum hydroxide) and cimetidine (in cases of constipation). In cases of hyperphosphatemic tetany (>8 mmol/L), diuresis is required.

Correcting the hypocalcemia once plasma phosphorus levels have been reduced to below 2.5 mmol/L or the solubility index is below 9. Failure to control hyperphosphatemia prior to calcium therapy will elevate the solubility index and may cause soft tissue mineralization. Hypocalcemic tetany occurs as calcium levels fall below 0.8 mmol/L. Correction is achieved by the slow intravenous infusion of calcium to effect. Oral calcium supplements (such as Neo-Calglucon and Nutrobal) are useful for long term calcium therapy but the benefit of vitamin D3 therapy must be weighed against the dangers of iatrogenic hypercalcemia and soft tissue mineralization. The use of full spectrum light sources (e.g., Zoo Med Reptisun 5.0 or Iguana light) or better still sunlight is safer. Monitor Ca:P ratios on a regular basis.

Preventing dehydration by maintaining humidity and adding water to food items.

Considering anabolic steroids and vitamin B complex every 7-28 d.

Avoiding nephrotoxic drugs and undue stress (proper husbandry) to the lizard.

(From January 1995 to January 1996, the author has treated 23 cases of chronic renal failure in lizards, 5 cases (22%) are known to have survived for longer than a year.)

If, as clinicians, we fail to resolve acute renal failure or permit chronic renal disease to progress unhindered then the outcome will be gout (visceral and articular). Acute gouty episodes may be treated symptomatically but widespread visceral gout is the result of end stage kidney disease and the prognosis is usually hopeless [4].

Literature Cited

1. Barten, S.L. (1996). Lizards. In: Reptile Medicine and Surg&y (Ed. D.R. Mader), p 47-61. WB Saunders, Philadelphia.

2. Divers, S.J., Redmayne, G. and Aves, E.K. (1996). Hematological and biochemical values of 10 green iguana (Iguana iguana). Veterinary Record 138:203-205.

3. Frye, F.L (1991). Comparative histology. In: Biomedical and Surgical Aspects of Captive Reptile Husbandry (Ed. FL Frye), p 488-501. Krieger, Malabar.

4. Mader, D.L. (1996). Gout. In: Reptile Medicine and Surgery (Ed. DR Mader), p 374-379. WB Saunders, Philadelphia. 5. Zwart, P. (1992). Urogenital systern. In: Manual of Reptiles (Eds. P.H. Beynon, M.P.C. Lawton and J.E. Cooper), p 117-120. BSAVA, Cheltenham.

TABLE 1 Blood Parameters in Iguana iguana Used in the Assessment of Renal Disease