Introduction
Urolithiasis is commonly reported in reptiles housed in zoological institutions and kept as companion animals.1–11 However, although urolithiasis is recognized as an important cause of urinary tract disease in reptiles, there is a paucity of information regarding the diagnosis and treatment of this condition in lizards. Most of the available literature is focused on chelonians, with both case reports and retrospective reviews having been published.5,6
Clinicopathologic findings and treatment have been described for a small number of lizards with urolithiasis.1–3,7,11 Lizards may present with nonspecific clinical signs such as hyporexia and lethargy, and although a diagnosis can sometimes be made by means of coelomic palpation, radiography, ultrasonography, or CT is often needed to establish or corroborate the diagnosis.1–5,7,9 The objectives of the study reported here were to document the clinical signs, diagnosis, and treatment of urolithiasis in green iguanas (Iguana iguana) and to report on the composition of uroliths from green iguanas submitted to the Minnesota Urolith Center for analysis.
Materials and Methods
Clinical case selection
Medical record databases at the University of Illinois Veterinary Teaching Hospital, Veterinary Health Center at Kansas State University, James L. Voss Veterinary Teaching Hospital at Colorado State University, William R. Pritchard Veterinary Medical Teaching Hospital at the University of California-Davis, North Carolina Veterinary Teaching Hospital, University of Wisconsin Small Animal Clinic, and University of Florida Small Animal Hospital were searched from January 1, 1996, through December 31, 2020, to identify and retrieve records of green iguanas (Iguana iguana) with urolithiasis. Keywords used for the search included iguana, green iguana, urolith, urolithiasis, cystic calculi, and bladder stone. Each of the retrieved medical records was reviewed by a single investigator (AJC); cases were included if the diagnosis of urolithiasis had been confirmed by means of diagnostic imaging or direct visual observation during surgery or necropsy.
Urolith database case selection
Records of uroliths from green iguanas submitted between January 1, 1996, and December 31, 2020, to the Minnesota Urolith Center at the University of Minnesota College of Veterinary Medicine were reviewed. To minimize confounding of the data through inclusion of green iguanas with a history of recurrent urolithiasis, data related to recurrences and to the clinical cases identified through the multicenter records search were excluded. An email was sent by one of the authors (JPL) to each veterinary hospital who submitted at least 1 case to the Minnesota Urolith Center requesting the medical records. The email specified patient name, date of submission, and owner name to request participation in the study.
Medical records review
For each iguana, information extracted from the medical record consisted of signalment, clinical signs, and results of all diagnostic tests and surgical procedures. Owing to the retrospective nature of the study and multi-institutional approach, husbandry information such as diet, humidity, and temperature could not be collected. Sex was determined on the basis of secondary sexual characteristics or a history of laying eggs. When age was unknown, the time when the animal was in the care of its current owner was recorded. Plasma biochemical analyses and CBCs were performed at either a veterinary teaching hospital or outside a reference laboratory in accordance with standard methods established by the individual clinical pathology laboratory. For iguanas, standard plasma biochemical variables recorded included glucose, BUN, total protein, albumin, globulin, calcium, phosphorus, uric acid, sodium, potassium, and chloride concentrations and aspartate transaminase (AST) and creatine kinase (CK) activities. Standard CBC variables included Hct, total WBC count, and absolute concentrations of heterophils, eosinophils, basophils, lymphocytes, monocytes, and azurophils. For patients that had multiple CBCs and plasma biochemical analyses performed, only the results obtained closest to the time when urolithiasis was diagnosed (within 1 week of diagnosis) were evaluated. Radiographs and CT images were reviewed by a single investigator (AJC), and the number and location of calculi were recorded, along with any other abnormalities that were identified.
Calculi retrieved from the urinary tract were analyzed at the Minnesota Urolith Center. Briefly, mineral composition of uroliths was determined by polarization microscopy and infrared spectroscopy. A urolith without a nidus or shell that contained ≥ 70% of a single mineral was identified by that mineral. A urolith without a nidus or shell that contained < 70% of any single mineral was referred to as a mixed urolith. Compound uroliths were defined as having a central core or outer layer containing ≥ 70% of a single mineral with an outer layer or central core of a different mineral.
Data analysis
All data were assessed for normality with the Anderson-Darling test (RStudio version 1.3.1073; RStudio). Depending on the distribution, summary statistics (mean, SD, median, and range) were calculated for signalment data and CBC and plasma biochemical variables. Median survival time (MST) was calculated for all green iguanas with confirmed urolithiasis as the time from the date of diagnosis to the date of death from any cause. Iguanas in which the diagnosis was made at necropsy and iguanas euthanized within 24 hours after the diagnosis was made and did not receive any treatment (including supportive care) were excluded from outcome analysis.
Results
Clinical cases
Thirteen iguanas that met the inclusion criteria were identified through the multi-institutional medical records database search. This included 5 iguanas from the University of Illinois Veterinary Teaching Hospital, 5 from the William R. Pritchard Veterinary Medical Teaching Hospital at the University of California-Davis, 2 from the Veterinary Health Center at Kansas State University, and 1 from the James L. Voss Veterinary Teaching Hospital at Colorado State University. There were no cases identified that met the inclusion criteria from the North Carolina Veterinary Teaching Hospital, University of Wisconsin Small Animal Clinic, or University of Florida Small Animal Hospital. Confirmatory diagnostic tests included direct visualization during surgery (n = 7) or necropsy (5) and CT (1).
Urolith database cases
Between 1996 and 2020, the Minnesota Urolith Center received 132 submissions of uroliths from green iguanas from across the US. The 4 cases with uroliths submitted to the Minnesota Urolith Center identified through the multi-institutional medical records search were excluded from this list as well as multiple submissions for the same animal. Emails were then sent to the veterinarian or veterinary practice on file for the remaining 121 green iguana urolith submissions. Ten respondents replied to the email to share further information about the cases that they submitted. Eight green iguanas met the inclusion criteria for this study, with all 8 confirmed to have urolithiasis by direct visualization during surgery. The 8 green iguanas included 4 from private practice veterinary hospitals and 4 from zoological institutions.
Green iguanas
Of the 21 green iguanas that met the inclusion criteria for the study, 9 (43%) were sexually intact males, 11 (52%) were sexually intact females, and 1 (5%) was a spayed female. For the 19 iguanas for which information was available, median age at the time of diagnosis was 9 years (range, 2 to 24 years) and median weight was 1.91 kg (range, 0.87 to 3.70 kg).
The most common complaint at time of presentation was lethargy (n = 12), followed by constipation or straining to urinate or defecate (9) and decreased appetite (9). In 3 animals, urolithiasis was identified on routine health screenings with an absence of clinical signs.
Physical examination results
During physical examination, 12 of 21 (57%) green iguanas had a hard mass palpable in the caudal aspect of the coelom. A hard structure was palpable via digital cloacal examination in 1 case; medical records for the remainder of cases did not mention the results of a digital cloacal examination. The next-most common abnormality identified during physical examination of the 21 iguanas was dehydration (n = 11) followed by weakness or lethargy (7), pale mucous membranes (3), and straining to urinate (2).
Diagnostic test results
Results of a CBC performed at a veterinary teaching hospital (n = 9) or outside a reference laboratory (3) were available for 12 green iguanas. Plasma biochemistry results from 9 green iguanas were available. Most laboratories combined the monocyte and azurophil counts and reported the result as a total monocyte concentration; therefore, total monocyte counts were reported for the present study.
Hematologic abnormalities included leukocytosis (n = 4), absolute heterophilia (3), hemoconcentration (2), absolute monocytosis (1), and leukopenia (1).12,13 Review of plasma biochemical analyses revealed that 2 green iguanas had severe hypocalcemia and hyperphosphatemia resulting from suspected renal secondary hyperparathyroidism, although other differential diagnoses were not ruled out and a necropsy was not performed. An additional 3 green iguanas had a CK activity higher than the upper reference value, 1 of which also had a high AST activity. Two iguanas had hyperuricemia, 2 had hypernatremia, and 1 had hyperkalemia.
Urine was collected intraoperatively from 4 of the iguanas. A urinalysis was performed in 1 case, and cytologic examination did not reveal evidence of inflammation, infection, renal casts, or crystalluria. Aerobic bacterial culture was performed on the 4 urine samples collected intraoperatively, and all 4 samples were positive for bacteria. The most common bacteria isolate was Klebsiella spp (n = 3), followed by Salmonella spp (2) and Escherichia coli (1). For 2 iguanas, bacterial culture yielded > 1 organism. One iguana had a mixed infection with Klebsiella spp and E coli, and the second iguana was infected with Klebsiella spp and Salmonella spp. Results of antimicrobial susceptibility testing were not available for these cases.
Radiographs were available for review for 12 of the 21 iguanas. Radiographic projections commonly obtained included a standard dorsoventral whole-body image and a horizontal-beam lateral whole-body image. All 12 iguanas had a caudal coelomic radiopaque mass effect on radiographic images, consistent with uroliths; however, additional differential diagnoses such as gastrointestinal, reproductive, and coelomic disease could not be ruled out. Uroliths had a radiopaque laminar appearance and were located in the caudal region of the coelom (Figure 1). The number of calculi visualized in the urinary tract region on radiographic images ranged from 1 to 4. Ten iguanas had a single urolith visualized during review of radiographic images, whereas 2 iguanas had multiple small, ovoid radiopaque stones. Urolith size was recorded for 9 stones with a median length of 5.0 cm (range, 3.4 to 7.0 cm) and a median width of 3.3 cm (range, 2.1 to 5.7 cm). Other abnormalities observed during review of radiographic images included gastrointestinal dilation with gas (n = 4), coelomic effusion (3), multiple long bone fractures (1), and diffuse osteopenia (1). One iguana underwent radiography and CT of the coelom. The number and location of uroliths visualized on the radiographic images agreed with the number and location of those visualized on the CT images. Additional findings identified on CT images in this case included diffuse heterogenous contrast enhancement of the liver and mild focal gas accumulation within the urinary bladder.
Dorsoventral and right lateral radiographic views of a 9-year-old female green iguana (Iguana iguana) that was presented for lethargy and anorexia. Notice a large, round, radiopaque, lamellar structure characteristic of a urate urolith in the right caudal region of the coelom, gastrointestinal dilation (solid arrows), and a soft tissue mass effect in the caudodorsal aspect of the coelom. The distended bladder and renomegaly (dashed arrows) likely caused compression of the distal portion of the intestinal tract, leading to the clinical sign of straining.
Citation: Journal of the American Veterinary Medical Association 260, 10; 10.2460/javma.22.01.0035
Treatment
Fifteen of 21 (71%) iguanas underwent surgery to remove the uroliths. The predominant surgical approach was cystotomy via a ventral paramedian incision (n = 14) followed by cystectomy via a ventral paramedian incision (1). Surgical intervention was recommended for all iguanas included in the study, but not all clients chose to pursue this treatment. When surgical intervention was not pursued (n = 3), medical treatments included an NSAID (meloxicam, 2; ketoprofen, 1), antimicrobials (ceftazidime, 1; enrofloxacin, 2), SC crystalloid fluids (3), and tramadol (1). None of the 3 green iguanas treated with medical management had follow-up records available for review. Two of the iguanas that underwent surgery developed intraoperative complications and died. In both cases, intraoperative hemorrhage combined with dehydration prior to surgery was suspected as the primary cause of death. One animal died during recovery from anesthesia; however, the owner did not permit a necropsy. Of the 12 iguanas that survived following surgery until hospital discharge, 8 had clinical follow-up information available; MST was 39 months (range, 2 to 108 months), with 2 animals still alive at the time of final follow-up. Recurrent urolithiasis was identified on follow-up examinations in 3 iguanas. Two iguanas had a single episode of a recurrent cystolith 9 and 15 months after the initial surgery. One iguana had 2 subsequent cystoliths 1 and 2 years after the initial surgery. In all 3 cases, repeated cystotomies were performed, resulting in successful removal and a return to normal behavior and activity.
Necropsy results
Necropsy was performed on 5 of the 21 (24%) iguanas. The decision to euthanize or the cause of death was associated with urolithiasis in 4 of these cases. A 12-year-old male iguana with a cystolith was euthanized secondary to gastrointestinal obstruction and ileus. Necropsy revealed a cystolith with secondary bladder distention and renomegaly that had led to a colonic impaction. A 7-year-old female iguana was euthanized owing to severe decompensation after presenting for further evaluation of a traumatic injury. There was evidence of a cystolith that resulted in marked distention of the urinary bladder with secondary mucosal hyperplasia and multifocal epithelial necrosis (Figure 2). Two other iguanas (a 9-year-old female and a 10-year-old male) were euthanized secondary to decompensation from severe renal disease and concurrent cystoliths seen on radiographs. Both animals had cystoliths noted on necropsy along with multifocal glomerulonephritis, renal mineralization, bladder wall thickening, and cystitis. A 10-year-old male iguana died secondary to disseminated carcinomatosis and was found to have an incidental single cystolith, which was not associated with clinical important bladder wall thickening or cystitis.
Photograph of the urinary bladder of a 7-year-old female green iguana that was euthanized because of severe decompensation after presenting for further evaluation of a traumatic injury. Depicted is a large cystolith that resulted in marked distention of the urinary bladder with secondary mucosal hyperplasia and epithelial necrosis.
Citation: Journal of the American Veterinary Medical Association 260, 10; 10.2460/javma.22.01.0035
Urolith composition
Review of the 132 urolith submissions, including 11 from the clinical cases, indicated that most uroliths (n = 127 [96.2%]) were obtained from the bladder. Uroliths were also submitted from voided urine samples (n = 3), the kidney (1), and the urethra (1). All uroliths were composed of salts of uric acid. Ammonium acid urate (n = 12) and sodium acid urate (10) were specifically identified in a minority of cases, with the remaining 110 uroliths described as 100% salts of uric acid.
Discussion
All of the 132 calculi analyzed in the present study were composed of salts of uric acid. This is similar to previous case reports of urolithiasis in lizards.2,3,11 Lizards, like most reptiles, are uricotelic and thus excrete nitrogenous wastes in the form of uric acid.14,15 Uric acid is the end product of nitrogen metabolism, which occurs endogenously from de novo protein synthesis and tissue catabolism or exogenously from uric acid production.15 Exogenous uric acid production is dependent on diet and is particularly high when the diet is rich in animal protein.16 Given the retrospective nature of our study, dietary histories were unavailable for review; however, clinicians should obtain comprehensive dietary histories for any reptile presenting with signs of urolithiasis to evaluate the role that diet might have had in the development of this condition.
In the limited literature of urolithiasis in lizards, animals may present with nonspecific clinical signs such as hyporexia, lethargy, or weight loss, although tenesmus, obstipation, and hematochezia have also been reported.4,5,14 Although most of the green iguanas in the present study presented with nonspecific complaints unrelated to the urogenital system, 9 of the 21 (43%) iguanas presented for evaluation of constipation or straining to urinate or defecate. This is similar to previous case reports of urolithiasis in lizards, in which presenting complaints were reported as anorexia and straining during defecation and urate secretion.1–3 In contrast, most chelonians with urolithiasis do not present for clinical signs related to urination abnormalities.6 The inability of clients to distinguish between constipation and straining to urinate is likely related to a lack of client education; however, constipation may occur secondary to colonic obstruction resulting from distention of the urinary bladder with large cystoliths. In 4 of 12 iguanas in the present study, gastrointestinal gas dilation was seen on radiographs; thus, urolithiasis should be on a clinician’s differential diagnosis list for any green iguana presenting with signs of straining, regardless of whether the gastrointestinal tract or urinary tract is suspected to be the cause of straining.
Interestingly, urolithiasis was diagnosed on routine health examinations, with no premonitory signs, in 3 green iguanas in the present study. In all 3 cases, the diagnosis was made with whole-body radiography performed during these examinations, which underscores the importance of routine preventative health examinations in green iguanas. Similarly, a case of chronic urolithiasis in a San Esteban Island chuckwalla (Sauromalus varius) was initially diagnosed by means of whole-body radiography during examination for an unrelated condition.11 This case along with findings of the present study illustrates that lizards with urolithiasis, like chelonians, may not always present with clinical signs suggestive of urinary tract disease.5,6
Twelve of the 21 (57%) iguanas in the present study had a hard mass suggestive of urolithiasis palpable in the caudal portion of the coelom. Two previous case reports1,3 of cystoliths in green iguanas also identified a hard structure in the coelom on physical examination. This is in contrast to findings for chelonians, in which only 25% had palpable uroliths during prefemoral palpation.6 The second-most common abnormality identified during physical examination was dehydration (n = 11). In lizards, the epithelium of both the bladder (if present) and colon can absorb water.16 Therefore, chronic dehydration may lead to an increase in water absorption from the bladder and colon, which further concentrates urate excreta in the bladder and may predispose to urolith formation.
The green iguanas in the present study had few hematologic and biochemical abnormalities, which is similar to findings for chelonians and a San Esteban Island chuckwalla (Sauromalus varius) with recurrent urolithiasis.6,11 The most common hematologic abnormality was mild to moderate leukocytosis characterized by heterophilia, likely secondary to inflammation.
A urinalysis was performed in a single case in the present study; however, in reptiles, urinalysis can be useful for cytologic assessments of inflammation and infection, identification of renal casts or crystals, and potentially identification of other risk factors that may contribute to urolith formation.17,18 The most common bacteria cultured from the urine in the present study was Klebsiella spp.
All green iguanas in the present study had uroliths visible on standard radiographs. This is similar to previous case reports1,3,11 of urolithiasis in lizards, but contrasts with findings for chelonians, in which urate uroliths are not always visible on standard radiographs.6 Urate uroliths had a thick laminar appearance on radiographic images, presumed to represent repeated deposition of supersaturated crystalline material on the urolith surface.9 Green iguanas in this study most commonly had a single urolith.
Fifteen of the 21 green iguanas in this study underwent surgery for urolith removal, with 12 of these animals surviving at least until hospital discharge. The predominant surgical approach, cystotomy via a ventral paramedian incision, is similar to that described in previously published reports.1,3,7 A single green iguana had a cystectomy performed owing to suspected necrosis of the bladder wall noted intraoperatively; however, caution is advised with this surgery in species that rely heavily on the urinary bladder as a site of postrenal modification of waste.11 Two green iguanas developed fatal intraoperative complications secondary to hemorrhage and hypovolemia. The long postoperative survival times reported from these cases (MST, 39 months) supported that surgical intervention, despite its risks, can have successful outcomes.
Although necropsy was performed on only a small number of green iguanas of the present study (5/21), the high incidence of urolithiasis contributing to the decision to euthanize or to the cause of death in these animals (4/5) indicates that urolithiasis in this species is not a benign diagnosis and is associated with morbidity and mortality. In those 4 green iguanas, abnormalities identified during necropsy were primarily associated with the renal system. Green iguana owners should be informed of potential life-threatening outcomes including severe bladder expansion, extraluminal colonic obstruction, and necrosis of the bladder wall that may occur if urolithiasis is not treated. These findings are in line with the physiological and anatomic consequences of untreated urolithiasis in other species, including chelonians.5,6
The major limitation of this study was its retrospective nature and the fact that diagnostic approach, documentation of physical examination findings, and thoroughness of clinical data varied. Analyses were reliant on information available in medical reports generated by multiple veterinarians over the 25-year span of this study. Furthermore, husbandry information, including diet and environmental conditions, could not be collected.
The results of the present study demonstrated that green iguanas with urolithiasis may or may not present with clinical signs directly referable to the urinary tract. A caudal coelomic mass was palpated in most cases; however, few cases had physical examination findings directly related to the urinary tract. Radiography was a valuable confirmatory diagnostic test, but hematologic and biochemical changes were relatively nonspecific. Green iguanas that were surgically treated had long MSTs after surgery, suggesting that early identification and appropriate intervention should be pursued to correct this disease. To elucidate the etiology of this disease, future research assessing the comprehensive dietary and environmental history for green iguanas with urolithiasis is necessary.
Acknowledgments
No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.
The authors thank Drs. Miranda Sadar, Meg Sutherland-Smith, Kate Gustavsen, Sam Rivera, Brianne Phillips, Sherri Edgar, Lauren Powers, and Brandy Kragness for assistance in case selection and data acquisition.
References
- 1. ↑
An M-Y, Jang I-H, Fehr M. A case report: Iguana iguana with cystic calculus. J Vet Clin 1998;15(2):472–475.
- 2. ↑
Birke LL, Cespedes AM, Schachner ER, Lailvaux SP. Cystic calculus in a laboratory-housed green anole (Anolis carolinensis). Comp Med 2017;67(2):112–115.
- 3. ↑
Govendan PN, Ananthawijaya IGM, Jayawarditha AAG. Case report: urolith surgical removal in a green iguana (Iguana iguana) Article in Indonesian. J Vet 2018;19(1):143–147.
- 4. ↑
Johnson JG III, Watson MK. Diseases of the reptile renal system. Vet Clin North Am Exot Anim Pract 2020;23(1):115–129.
- 5. ↑
Keller KA. Urolithiasis (cystic calculi and cloacal uroliths). In: Divers SJ, Stahl SJ, eds. Mader’s Reptile and Amphibian Medicine and Surgery. 3rd ed. Elsevier Inc; 2019:1355–1356.
- 6. ↑
Keller KA, Hawkins MG, Weber EPS III, Ruby AL, Sanchez-Migallon Guzman D, Westropp JL. Diagnosis and treatment of urolithiasis in client-owned chelonians: 40 cases (1987–2012). J Am Vet Med Assoc 2015;247(6):650–658.
- 7. ↑
Kwantes LJ. Surgical correction of cystic urolithiasis in an iguana. Can Vet J 1992;33(11):752–753.
- 8.
Lightfoot T. Bladder necrosis secondary to cystic calculus in a green iguana. Exotic DVM. 1999;1(3):29–33.
- 9. ↑
Mader DR. Calculi: urinary. In: Mader DR, ed. Reptile Medicine and Surgery. 2nd ed. Saunders Elsevier; 2006:763–771.
- 10.
Magnotti JM, Garner MM, Stahl SJ, Corbin EM, LaDouceur EEB. Retrospective review of histologic findings in captive gila monsters (Heloderma suspectum) and beaded lizards (Heloderma horridum). J Zoo Wildl Med 2021;52(1):166–175.
- 11. ↑
Wolf KN, Troan BV, DeVoe R. Chronic urolithiasis and subsequent cystectomy in a San Esteban Island Chuckwalla, Sauromalus varius. J Herpetol Med Surg 2008;18(3):106–112.
- 12. ↑
Hanley CS, Hernandez-Divers SJ, Bush S, Latimer KS. Comparison of the effect of dipotassium ethylenediaminetetraacetic acid and lithium heparin on hematologic values in the green iguana (Iguana iguana). J Zoo Wildl Med 2004;35(3):328–332.
- 13. ↑
Harr KE, Alleman AR, Dennis PM, et al. Morphologic and cytochemical characteristics of blood cells and hematologic and plasma biochemical reference ranges in green iguanas. J Am Vet Med Assoc 2001;218(6):915–921.
- 15. ↑
Sartori MR, Taylor EW, Abe AS. Nitrogen excretion during embryonic development of the green iguana, Iguana iguana (Reptilia; Squamata). Comp Biochem Physiol A Mol Integr Physiol. 2012;163(2):210–214.
- 16. ↑
Holz PH. Anatomy and physiology of the reptile renal system. Vet Clin North Am Exot Anim Pract 2020;23(1):103–114.
- 17. ↑
Dantzler WH, Braun EJ. Comparative nephron function in reptiles, birds, and mammals. Am J Physiol 1980;239(3):R197–R213.
- 18. ↑
Mader D. Reptile urinary system: clinical evaluation. In: Proceedings of the Association of Reptilian and Amphibian Veterinarians. Association of Reptilian and Amphibian Veterinarians; 2013:79–83.
