High Prevalence of Lesions of Systemic Hypertension in Bile-Extracted Asiatic Black Bears (Ursus thibetanus) and Associated Renal Disease
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Data for Analysis
2.3. Sampling Procedure
2.4. Age Estimations
2.5. Lesions of Systemic Hypertension
2.6. Renal Disease
2.7. Statistical Analysis
3. Results
3.1. Demographics
3.2. Systemic Hypertension Lesions
3.3. Renal Disease Parameters
3.4. Associations Between Renal Disease and Lesions of Systemic Hypertension
3.5. Additional Descriptive Evidence of Renal Disease in Bile-Extracted Bears
4. Discussion
5. Limitations
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CITES | Convention on the International Trade of Endangered Species of Wild Fauna and Flora |
SDMA | Symmetric dimethylarginine |
SHT | Systemic hypertension |
SHT-0 | Category of bears with no lesions of systemic hypertension |
SHT-1 | Category of bears with one or more lesions of systemic hypertension |
UPC | Urine protein:creatinine ratio |
References
- Appiah, S.; Revitt, M.; Jones, H.; Vu, M.; Simmonds, M.; Bell, C. Antiinflammatory and hepatoprotective medicinal herbs as potential substitutes for bear bile. Int. Rev. Neurobiol. 2017, 135, 149–180. [Google Scholar] [PubMed]
- Garshelis, D.; Steinmetz, R. Ursus thibetanus (Amended Version of 2016 Assessment). In The IUCN Red List of Threatened Species; E.T22824A166528664; 2020; Available online: https://www.iucnredlist.org/ (accessed on 11 April 2025). [CrossRef]
- Still, J. Use of animal products in traditional Chinese medicine: Environmental impact and health hazards. Complement. Ther. Med. 2003, 11, 118–122. [Google Scholar] [CrossRef]
- CITES (Convention on International Trade in Endangered Species of Wild Fauna and Flora). Asiatic Black Bear. Available online: https://cites.org/eng/gallery/species/mammal/Asiatic_black_bear.html (accessed on 11 April 2025).
- Feng, Y.; Siu, K.; Wang, N.; Ng, K.M.; Tsao, S.W.; Nagamatsu, T.; Tong, Y. Bear bile: Dilemma of traditional medicinal use and animal protection. J. Ethnobiol. Ethnomed. 2009, 5, 2. [Google Scholar] [CrossRef] [PubMed]
- Loeffler, I.K.; Robinson, J.; Cochrane, G. Compromised health and welfare of bears farmed for bile in China. Anim. Welf. 2009, 18, 225–235. [Google Scholar] [CrossRef]
- Maas, B. The Veterinary, Behavioural and Welfare Implications of Bear Farming in Asia; World Society for the Protection of Animals: London, UK, 2000. [Google Scholar]
- Li, P.J. Rehabilitating rescued Chinese farm bears (Ursus thibetanus): Results, limitations, and implications. J. Wildl. Rehabil. 2004, 27, 4–15. [Google Scholar]
- Bando, M.K.H.; Nelson, O.L.; Webster, N.; Ramsay, J.D.; Bacon, H.J.; Sellon, R. Aortic aneurysm, dissection, and rupture in six bile-farmed bears. J. Zoo Wildl. Med. 2018, 49, 738–747. [Google Scholar] [CrossRef]
- Acierno, M.J.; Brown, S.; Coleman, A.E.; Jepson, R.E.; Papich, M.; Stepien, R.L.; Syme, H.M. ACVIM consensus statement: Guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J. Vet. Intern. Med. 2018, 32, 1803–1822. [Google Scholar] [CrossRef]
- Fernandez-Moure, J.S.; Vykoukal, D.; Davies, M.G. Biology of aortic aneurysms and dissections. Methodist Debakey Cardiovasc. J. 2011, 7, 2–7. [Google Scholar] [CrossRef]
- Wey, A.C.; Atkins, C.E. Aortic dissection and congestive heart failure associated with systemic hypertension in a cat. J. Vet. Intern. Med. 2000, 14, 208–213. [Google Scholar] [CrossRef]
- Kenny, D.E.; Cambre, R.C.; Alvarado, T.P.; Prowten, A.W.; Allchurch, A.F.; Marks, S.K.; Zuba, J.R. Aortic dissection: An important cardiovascular disease in captive gorillas (Gorilla gorilla gorilla). J. Zoo Wildl. Med. 1994, 25, 561–568. [Google Scholar]
- Brown, S.; Atkins, C.; Bagley, R.; Carr, A.; Cowgill, L.; Davidson, M.; Egner, B.; Elliott, J.; Henik, R.; Labato, M.; et al. ACVIM consensus statement guidelines for the identification, evaluation, and management of systemic hypertension in dogs and cats. J. Vet. Intern. Med. 2007, 21, 542–558. [Google Scholar] [CrossRef] [PubMed]
- Jepson, R.E. Feline systemic hypertension. J. Feline Med. Surg. 2011, 13, 25–34. [Google Scholar] [CrossRef]
- Syme, H. Hypertension in small animal kidney disease. Vet. Clin. N. Am. Small Anim. Pract. 2011, 41, 63–89. [Google Scholar] [CrossRef] [PubMed]
- Bando, M.K.H.; Nelson, O.L.; Kogan, C.; Sellon, R.; Wiest, M.; Bacon, H.J.; Hunter-Ishikawa, M.; Leadbeater, W.; Yamazaki, K.; Jin, Y.; et al. Metabolic derangements and reduced survival of bile-extracted Asiatic black bears (Ursus thibetanus). BMC Vet. Res. 2019, 15, 263. [Google Scholar] [CrossRef] [PubMed]
- Hachiya, N.; Ohtaishi, N. Methods of Preparing Osteal Specimens; Hokkaido University Press: Sapporo, Japan, 1994. (In Japanese) [Google Scholar]
- Nelson, O.L.; Reidesel, E.; Ware, W.A.; Christensen, W.F. Echocardiographic and radiographic changes associated with systemic hypertension in cats. J. Vet. Intern. Med. 2002, 16, 418–425. [Google Scholar] [CrossRef]
- Niemuth, J.N.; De Voe, R.S.; Jennings, S.H.; Loomis, M.R.; Troan, B.V. Malignant hypertension and retinopathy in a western lowland gorilla (gorilla gorilla gorilla). J. Med. Primatol. 2014, 43, 276–279. [Google Scholar] [CrossRef]
- Boon, J.A. Veterinary Echocardiography, 2nd ed.; Wiley-Blackwell: Ames, IA, USA, 2011. [Google Scholar]
- De Madron, E.; Chetboul, V.; Bussadori, C. Clinical Echocardiography of the Dog and Cat; Elsevier Health Sciences: St Louis, MO, USA, 2015. [Google Scholar]
- ZIMS Expected Test Results for Ursus thibetanus/Asiatic Black Bear. (Last Global Update 06/05/2025). Species360 Zoological Information Management System Version 2.25.5. [Asiatic Black Bear]. Available online: http://zims.Species360.org (accessed on 20 May 2025).
- Rentko, V.; Nabity, M.; Yerramilli, M.; Obare, E.; Yerramilli, M.; Aguiar, J.; Relford, R. Determination of serum symmetric dimethylarginine reference limit in clinically healthy dogs. J. Vet. Intern. Med. 2013, 27, 750. [Google Scholar]
- Cianciolo, R.E.; Mohr, F.C.; Aresu, L.; Brown, C.A.; James, C.; Jansen, J.H.; Spangler, W.L.; van der Lugt, J.J.; Kass, P.H.; Brovida, C.; et al. World small animal veterinary association renal pathology initiative: Classification of glomerular diseases in dogs. Vet. Pathol. 2016, 53, 113–135. [Google Scholar] [CrossRef]
- R Development Core Team. R: A Language and Environment for Statistical Computing; R Foundation for Statistical Computing: Vienna, Austria, 2018. [Google Scholar]
- van Buren, S.; Groothuis-Oudshoorn, K. Mice: Multivariate imputation by chained equations in r. J. Stat. Softw. 2011, 45, 1–67. [Google Scholar] [CrossRef]
- Harrell, F.E. Rms: Regression Modeling Strategies; Springer: Berlin/Heidelberg, Germany, 2018. [Google Scholar]
- Poulter, N.R.; Prabhakaran, D.; Caulfield, M. Hypertension. Lancet 2015, 386, 801–812. [Google Scholar] [CrossRef]
- Staessen, J.A.; Wang, J.; Bianchi, G.; Birkenhäger, W.H. Essential hypertension. Lancet 2003, 361, 1629–1641. [Google Scholar] [CrossRef] [PubMed]
- Brown, S.A.; Henik, R.A. Diagnosis and treatment of systemic hypertension. Vet. Clin. N. Am. Small Anim. Pract. 1998, 28, 1481–1494. [Google Scholar] [CrossRef]
- Rivet, D.R.; Nelson, O.L.; Vella, C.A.; Jansen, H.T.; Robbins, C.T. Systemic effects of a high saturated fat diet in grizzly bears (Ursus arctos horribilis). Can. J. Zool. 2017, 95, 797–807. [Google Scholar] [CrossRef]
- Caulkett, N.A.; Cattet, M.R.L. Physiological effects of medetomidine-zolazepam-tiletamine immobilization in black bears. J. Wildl. Dis. 1997, 33, 618–622. [Google Scholar] [CrossRef] [PubMed]
- Caulkett, N.A.; Cattet, M.R.L.; Caulkett, J.M.; Polischuk, S.C. Comparative physiologic effects of telazol, medetomidine-ketamine, and medetomidine-telazol in captive polar bears. J. Zoo Wildl. Med. 1999, 30, 504–509. [Google Scholar]
- Grosso, A.; Veglio, F.; Porta, M.; Grignolo, F.M.; Wong, T.Y. Hypertensive retinopathy revisited: Some answers, more questions. British J. Ophthalmol. 2005, 89, 1646–1654. [Google Scholar] [CrossRef]
- Goyal, J.L.; Gupta, A.; Gandhi, P. Ocular Manifestations in Renal Disease. Indian J. Ophthalmol. 2023, 71, 2938–2943. [Google Scholar] [CrossRef]
- Gudayneh, Y.A.; Shumye, A.F.; Gelaye, A.T.; Tegegn, M.T. Prevalence of hypertensive retinopathy and its associated factors among adult hypertensive patients attending comprehensive specialized hospitals in northwest Ethiopia, 2024, a multicenter cross-sectional study. Int. J. Retin. Vitreous. 2025, 11, 17. [Google Scholar] [CrossRef] [PubMed]
- Porta, M.; Grosso, A.; Veglio, F. Hypertensive retinopathy: There’s more than meets the eye. J. Hypertens. 2005, 23, 683–696. [Google Scholar] [CrossRef]
- Shigematsu, Y.; Hamada, M.; Ohtsuka, T.; Hashida, H.; Ikeda, S.; Kuwahara, T.; Hara, Y.; Kodama, K.; Hiwada, K. Left ventricular geometry as an independent predictor for extracardiac target organ damage in essential hypertension. Am. J. Hypertens. 1998, 11, 1171–1177. [Google Scholar] [CrossRef]
- Lawson, J.S.; Jepson, R.E. Feline Comorbidities: The intermingled relationship between chronic kidney disease and hypertension. J. Feline Med. Surg. 2021, 23, 812–822. [Google Scholar] [CrossRef] [PubMed]
- Mahadappa, P.; Jeyaraja, K.; Thirunavakkarasu, P.S.; Krishnaswamy, N. Association between systolic blood pressure and target organ damage in naturally occurring cases of systemic hypertension in the dog. Top. Companion Anim. Med. 2024, 58, 100843. [Google Scholar] [CrossRef]
- LeBlanc, N.L.; Stepien, R.L.; Bentley, E. Ocular lesions associated with systemic hypertension in dogs: 65 cases (2005–2007). J. Am. Vet. Med. Assoc. 2011, 238, 915–921. [Google Scholar] [CrossRef]
- Lowenstine, L.J.; McManamon, R.; Terio, K.A. Comparative pathology of aging great apes: Bonobos, chimpanzees, gorillas, and orangutans. Vet. Pathol. 2016, 53, 250–276. [Google Scholar] [CrossRef] [PubMed]
- Campese, V.M.; Mitra, N.; Sandee, D. Hypertension in renal parenchymal disease: Why is it so resistant to treatment? Kidney Int. 2006, 69, 967–973. [Google Scholar] [CrossRef]
- Henik, R.A. Systemic hypertension and its management. Vet. Clin. N. Am. Small Anim. Pract. 1997, 27, 1355–1372. [Google Scholar] [CrossRef] [PubMed]
- Kalra, P.A. Renal specific secondary hypertension. J. Ren. Care 2007, 33, 4–10. [Google Scholar] [CrossRef]
- Leclerc, A.; Trehiou-Sechi, E.; Gruenz, E.M.; Damoiseaux, C.; Bouvard, J.; Chetboul, V. Systemic arterial hypertension secondary to chronic kidney disease in two captive-born large felids. J. Vet. Cardiol. 2017, 19, 308–316. [Google Scholar] [CrossRef]
- Cowgill, L.D.; Polzin, D.J.; Elliot, J.; Nabity, M.B.; Segev, G.; Grauer, G.F.; Brown, S.; Langston, C.; van Dongen, A.M. Is progressive chronic kidney disease a slow acute kidney injury? Vet. Clin. Small Anim. 2016, 46, 995–1013. [Google Scholar] [CrossRef]
- López-Novoa, J.M.; Rodríguez-Peña, A.B.; Ortiz, A.; Martínez-Salgado, C.; Hernández, F.J.L. Etiopathology of chronic tubular, glomerular and renovascular nephropathies: Clinical implications. J. Transl. Med. 2011, 9, 13. [Google Scholar] [CrossRef]
- Jepson, R.E. Current understanding of the pathogenesis of progressive chronic kidney disease in cats. Vet. Clin. N. Am. Small Anim. Pract. 2016, 46, 1015–1048. [Google Scholar] [CrossRef] [PubMed]
- Ross, L. Acute kidney injury in dogs and cats. Vet. Clin. Small Anim. 2011, 41, 1–14. [Google Scholar] [CrossRef]
- Li, P.J. China’s bear farming and long-term solutions. J. Appl. Anim. Welf. Sci. 2004, 7, 71–80. [Google Scholar] [CrossRef] [PubMed]
- Nabity, M.B.; Lees, G.E.; Boggess, M.M.; Yerramilli, M.; Obare, E.; Yerramilli, M.; Rakitin, A.; Aguiar, J.; Relford, R. Symmetric dimethylarginine assay validation, stability, and evaluation as a marker for the early detection of chronic kidney disease in dogs. J. Vet. Intern. Med. 2015, 29, 1036–1044. [Google Scholar] [CrossRef] [PubMed]
- Hall, J.A.; Yerramilli, M.; Obare, E.; Yerramilli, M.; Jewell, D.E. Comparison of serum concentrations of symmetric dimethylarginine and creatinine as kidney function biomarkers in cats with chronic kidney disease. J. Vet. Intern. Med. 2014, 28, 1676–1683. [Google Scholar] [CrossRef] [PubMed]
- Lamglait, B.; Vandenbunder-Beltrame, M. Evaluation of symmetric dimethylarginine as an early biomarker of chronic kidney disease in captive cheetahs (Acinonyx jubatus). J. Zoo Wildl. Med. 2017, 48, 874–877. [Google Scholar] [CrossRef]
- Relford, R.; Robertson, J.; Clements, C. Symmetric dimethylarginine: Improving the diagnosis and staging of chronic kidney disease in small animals. Vet. Clin. N. Am. Small Anim. Pract. 2016, 46, 941–960. [Google Scholar] [CrossRef]
- Buresova, E.; Stock, E.; Paepe, D.; Stammeleer, L.; Vandermeulen, E.; Smets, P.; Duchateau, L.; Lefebvre, H.P.; Daminet, S. Assessment of symmetric dimethylarginine as a biomarker of renal function in hyperthyroid cats treated with radioiodine. J. Vet. Intern. Med. 2019, 33, 516–522. [Google Scholar] [CrossRef]
- Cianciolo, R.E.; Benali, S.L.; Aresu, L. Aging in the canine kidney. Vet. Pathol. 2016, 53, 299–308. [Google Scholar] [CrossRef]
- Pickering, T.G. Mental stress as a causal factor in the development of hypertension and cardiovascular disease. Curr. Hypertens. Rep. 2001, 3, 249–254. [Google Scholar] [CrossRef]
- Morgan, K.N.; Tromborg, C.T. Sources of stress in captivity. Appl. Anim. Behav. Sci. 2007, 102, 262–302. [Google Scholar] [CrossRef]
- Malcolm, K.D.; McShea, W.J.; Van Deelen, T.R.; Bacon, H.J.; Liu, F.; Putman, S.; Zhu, X.; Brown, J.L. Analyses of fecal and hair glucocorticoids to evaluate short- and long-term stress and recovery of Asiatic black bears (Ursus thibetanus) removed from bile farms in China. Gen. Comp. Endocrinol. 2013, 185, 97–106. [Google Scholar] [CrossRef] [PubMed]
Glomerular Tufts/ Corpuscles | Interstitium | Vascular | Tubules |
---|---|---|---|
Hypercellularity | Fibrosis | Medial hypertrophy | Tubular necrosis |
Neutrophils | Inflammation | Arterial hyalinosis | Single cell necrosis |
Increased mesangium | Edema | Regeneration | |
Obsolescence | Hemorrhage | Proteinosis | |
Synechia | Intratubular crystals | ||
Bowman’s space ectasia | Epithelial cell pigment | ||
Parietal cell hypertrophy | Intraluminal pigment | ||
Crescent/fibrin | Tubulitis | ||
Capsular thickening | Dilation/Ectasia | ||
Protein in Bowman’s space |
Demographics | Females | Males | Total |
---|---|---|---|
Number of bears | 115 (64%) | 65 (36%) | 180 |
Mean Age a (years) ± SD (range) | 17 ± 4.7 (5–27) | 18 ± 4.4 (3–28) | 17 ± 4.6 (3–28) |
Status | |||
Living Dead | 67 (58.3%) 48 (41.7%) | 32 (49.3%) 33 (50.7%) | 99 (55%) 81 (45%) |
Hypertension Category: | |||
SHT-0 SHT-1 | 28 (24.3%) 87 (75.7%) | 15 (23.1%) 50 (76.9%) | 43 (23.9%) 137 (76.1%) |
SHT-0 (n = 43) | SHT-1 (n = 137) | p-Value | |
---|---|---|---|
Female | 28 (65.1%) | 87 (63.5%) | |
Male | 15 (34.9%) | 50 (36.5%) | |
Median Age a (yrs) (range) (n = 164) | 13 (8–21) | 11 (1–28) | 0.2503 b |
Median Serum CREA (µmol/L) (range) (n = 169) | 140 (59–503) | 153 (53–1516) | 0.0168 c |
Median Serum SDMA (µg/dL) (range) (n = 81) | 12 (8–33) | 12 (7–100) | 0.3664 c |
Median Renal Histopathology Score (range) (n = 81) | 3 (0–24) | 8 (0–29) | 0.0003 c |
SHT-0 (n = 18) | SHT-1 (n = 63) | |
---|---|---|
Mean Age at Death a (years) ± SD (range) | 16 ± 3.3 (9–21) | 17 ± 4.8 (7–28) |
Glomerular Tuft Lesions: | No. of bears (%) | No. of bears (%) |
Obsolescence (n = 40) | 3 (16.7%) | 37 (58.7%) |
Bowman’s space ectasia (n = 40) | 6 (33.3%) | 34 (54.0%) |
Increased mesangium (n = 26) | 3 (16.7%) | 23 (36.5%) |
Capsular thickening (n = 25) | 1 (5.6%) | 24 (38.1%) |
Protein (n = 24) | 4 (22.2%) | 20 (31.7%) |
Synechia (n = 11) | 1 (5.6%) | 10 (15.9%) |
Interstitial Lesions | ||
Fibrosis (n = 59) | 6 (33.3%) | 53 (84.1%) |
Inflammation (n = 36) | 4 (22.2%) | 32 (50.8%) |
Tubular Lesions | ||
Dilation/Ectatic (n = 45) | 6 (33.3%) | 39 (61.9%) |
Proteinosis (n = 41) | 7 (38.9%) | 34 (54.0%) |
Regeneration (n = 20) | 1 (5.6%) | 19 (30.2%) |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Bando, M.K.H.; Nelson, O.L.; Taylor, K.; Sellon, R.; Kogan, C.; Robinson, J.; Drayton, E.; Hartley, C.; Donaldson, D.; Linney, C.; et al. High Prevalence of Lesions of Systemic Hypertension in Bile-Extracted Asiatic Black Bears (Ursus thibetanus) and Associated Renal Disease. Animals 2025, 15, 1940. https://doi.org/10.3390/ani15131940
Bando MKH, Nelson OL, Taylor K, Sellon R, Kogan C, Robinson J, Drayton E, Hartley C, Donaldson D, Linney C, et al. High Prevalence of Lesions of Systemic Hypertension in Bile-Extracted Asiatic Black Bears (Ursus thibetanus) and Associated Renal Disease. Animals. 2025; 15(13):1940. https://doi.org/10.3390/ani15131940
Chicago/Turabian StyleBando, Monica K. H., O. Lynne Nelson, Kyle Taylor, Rance Sellon, Clark Kogan, Jill Robinson, Emily Drayton, Claudia Hartley, David Donaldson, Chris Linney, and et al. 2025. "High Prevalence of Lesions of Systemic Hypertension in Bile-Extracted Asiatic Black Bears (Ursus thibetanus) and Associated Renal Disease" Animals 15, no. 13: 1940. https://doi.org/10.3390/ani15131940
APA StyleBando, M. K. H., Nelson, O. L., Taylor, K., Sellon, R., Kogan, C., Robinson, J., Drayton, E., Hartley, C., Donaldson, D., Linney, C., & Stephenson, H. (2025). High Prevalence of Lesions of Systemic Hypertension in Bile-Extracted Asiatic Black Bears (Ursus thibetanus) and Associated Renal Disease. Animals, 15(13), 1940. https://doi.org/10.3390/ani15131940