Editorial Type:
Scientific Reports

Blood concentration of symmetric dimethylarginine correlates with kidney damage as assessed with a proposed histologic grading system for chronic kidney disease in tigers (Panthera tigris)

Blake J. AndrewsMr. Andrews was a third-year veterinary student at the College of Veterinary Medicine, University of Tennessee, Knoxville, TN, when the report was written.

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Andrew C. CushingDepartment of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN

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Rachel E. MurphyIdexx Laboratories, Inc, Westbrook, ME

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Emily M. WilsonIn-Sync Exotics Wildlife Rescue & Educational Center, Wylie, TX

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Mee-Ja M. SulaBiomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN

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DOI:
https://doi.org/10.2460/javma.21.04.0216
Volume/Issue:
Volume 260: Issue 13
Online Publication Date:
13 Apr 2022
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Abstract

OBJECTIVE

To determine the utility of blood symmetric dimethylarginine (SDMA) concentration measurement as a diagnostic tool for chronic kidney disease (CKD) in tigers (Panthera tigris) by comparing results for SDMA with those for traditional renal biomarkers and investigating correlations between these biomarkers and histopathologic kidney changes in tigers with CKD.

SAMPLE

Blood, urine, and kidney samples from 35 tigers with CKD from 2 sanctuaries.

PROCEDURES

Blood (serum or plasma) and urine samples were collected antemortem. Necropsy, including gross and histologic assessment, was performed for tigers that died or were euthanized for quality-of-life reasons. Results for CKD biomarkers in blood (BUN, creatinine, phosphorus, and SDMA concentrations) and urine (protein concentration, urine protein-to-creatinine ratio, and urine specific gravity) were evaluated for correlation with histologic kidney damage scored with an objective grading scale defined by percentage of inflammation, fibrosis, and tubular atrophy.

RESULTS

Symmetric dimethylarginine had the strongest significant correlation (ρ = 0.667) with histologic kidney damage score, followed by urine specific gravity (ρ = –0.639), blood creatinine concentration (ρ = 0.624), and BUN (ρ = 0.588). No significant correlation with kidney score was identified for blood phosphorus concentration, urine protein concentration, or the urine protein-to-creatinine ratio.

CLINICAL RELEVANCE

We recommend SDMA be prioritized as a renal biomarker in tigers, with SDMA results considered in addition to those of other traditional renal biomarkers when assessing kidney function in tigers. Additionally, the grading scale we developed could be replicated across patients and pathologists for more consistent postmortem assessment of CKD in tigers.

Abstract

OBJECTIVE

To determine the utility of blood symmetric dimethylarginine (SDMA) concentration measurement as a diagnostic tool for chronic kidney disease (CKD) in tigers (Panthera tigris) by comparing results for SDMA with those for traditional renal biomarkers and investigating correlations between these biomarkers and histopathologic kidney changes in tigers with CKD.

SAMPLE

Blood, urine, and kidney samples from 35 tigers with CKD from 2 sanctuaries.

PROCEDURES

Blood (serum or plasma) and urine samples were collected antemortem. Necropsy, including gross and histologic assessment, was performed for tigers that died or were euthanized for quality-of-life reasons. Results for CKD biomarkers in blood (BUN, creatinine, phosphorus, and SDMA concentrations) and urine (protein concentration, urine protein-to-creatinine ratio, and urine specific gravity) were evaluated for correlation with histologic kidney damage scored with an objective grading scale defined by percentage of inflammation, fibrosis, and tubular atrophy.

RESULTS

Symmetric dimethylarginine had the strongest significant correlation (ρ = 0.667) with histologic kidney damage score, followed by urine specific gravity (ρ = –0.639), blood creatinine concentration (ρ = 0.624), and BUN (ρ = 0.588). No significant correlation with kidney score was identified for blood phosphorus concentration, urine protein concentration, or the urine protein-to-creatinine ratio.

CLINICAL RELEVANCE

We recommend SDMA be prioritized as a renal biomarker in tigers, with SDMA results considered in addition to those of other traditional renal biomarkers when assessing kidney function in tigers. Additionally, the grading scale we developed could be replicated across patients and pathologists for more consistent postmortem assessment of CKD in tigers.

Supplementary Materials

    • Supplementary Figure S1 (PDF 95 KB)
    • Supplementary Figure S2 (PDF 93 KB)
    • Supplementary Figure S3 (PDF 95 KB)
    • Supplementary Figure S4 (PDF 213 KB)

Contributor Notes

Corresponding author: Dr. Cushing (acushin1@utk.edu)
Cover Journal of the American Veterinary Medical Association
Journal of the American Veterinary Medical Association
ISSN:
0003-1488
Publication Date:
13 Apr 2022
  • 1.

    Lund EM, Armstrong PJ, Kirk CA, Kolar LM, Klausner JS. Health status and population characteristics of dogs and cats examined at private veterinary practices in the United States. J Am Vet Med Assoc. 1999;214(9):1336–1341.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Norton BB, Tunseth D, Holder K, Briggs M, Hayek LC, Murray S. Causes of morbidity in captive African lions (Panthera leo) in North America, 2001–2016. Zoo Biol. 2018;37(5):354–359.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Waugh L, Lyon S, Cole GA, et al. Retrospective analysis and validation of serum symmetric dimethylarginine (SDMA) concentrations in cheetahs (Acinonyx jubatus). J Zoo Wildl Med. 2018;49(3):623–631.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Lee SW, Elfadl AK, Chung MJ, et al. Urocystitis, pyelonephritis, renal papillary necrosis and chronic tubulointerstitial disease causing chronic renal insufficiency in a Siberian tiger (Panthera tigris altaica): a case report. Vet Med-Czech. 2018;63:482–487.

    • Search Google Scholar
    • Export Citation
  • 5.

    Hokamp JA, Nabity MB. Renal biomarkers in domestic species. Vet Clin Pathol. 2016;45(1):28–56.

  • 6.

    Kovarikova S. Indirect markers of glomerular filtration rate in dogs and cats: a review. Vet Med-Czech. 2018;63:395–412.

  • 7.

    Braff J, Obare E, Yerramilli M, Elliott J, Yerramilli M. Relationship between serum symmetric dimethylarginine concentration and glomerular filtration rate in cats. J Vet Intern Med. 2014;28(6):1699–1701.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Hall JA, Yerramilli M, Obare E, Yerramilli M, Jewell DE. 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(6):1676–1683.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Nabity MB, Lees GE, Boggess MM, et al. 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(4):1036–1044.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Di Girolamo N, Huynh M. Disorders of the Urinary and Reproductive Systems in Ferrets. In: Quesenberry KE, Orcutt CJ, Mans C, et al., eds. Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery. 4th ed. Elsevier; 2021:39–54.

    • Search Google Scholar
    • Export Citation
  • 11.

    Finco DR, Brown SA, Vaden SL, Ferguson SA. Relationship between plasma creatinine concentration and glomerular filtration rate in dogs. J Vet Pharmacol Ther. 1995;18(6):418–421.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Mota SM, Brandão J, Guthrie A. Comparison of blood symmetric dimethylarginine and creatinine as endogenous markers of kidney function in captive tigers (Panthera tigris). J Zoo Wildl Med. 2021;52(2):628–637.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Médaille C, Trumel C, Concordet D, Vergez F, Braun JP. Comparison of plasma/serum urea and creatinine concentrations in the dog: a 5-year retrospective study in a commercial veterinary clinical pathology laboratory. J Vet Med A Physiol Pathol Clin Med. 2004;51(3):119–123.

    • Search Google Scholar
    • Export Citation
  • 14.

    Miyagawa Y, Takemura N, Hirose H. Assessments of factors that affect glomerular filtration rate and indirect markers of renal function in dogs and cats. J Vet Med Sci. 2010;72(9):1129–1136.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Longley L. Aging in large felids. In: Miller R, Fowler M, eds. Fowler’s Zoo and Wild Animal Medicine. 7th ed. Elsevier Saunders; 2012:465–469.

    • Search Google Scholar
    • Export Citation
  • 16.

    Hall JA, Yerramilli M, Obare E, Yerramilli M, Melendez LD, Jewell DE. Relationship between lean body mass and serum renal biomarkers in healthy dogs. J Vet Intern Med. 2015;29(3):808–814.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17.

    Relford R, Robertson J, Clements C. Symmetric dimethylarginine improving the diagnosis and staging of chronic kidney disease in small animals. Vet Clin North Am Small Anim Pract. 2016;46(6):941–960.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    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(3):874–877.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19.

    Cannon M. Diagnosis and investigation of chronic kidney disease in cats. In Pract. 2016;38:2–9.

  • 20.

    Huaijantug S, Manatpreprem K, Manatpreprem S, Yatmark P. Ultrasonographic evaluation of the renal dimensions in captive tigers. J Vet Med Sci. 2017;78(12):1759–1763.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21.

    Newkirk KM, Newman SJ, White LA, Rohrbach BW, Ramsay EC. Renal lesions of nondomestic felids. Vet Pathol. 2011;48(3):698–705.

  • 22.

    Giraldi M, Rossi G, Bertazzolo W, Negri N, Paltrinieri S, Scarpa P. Evaluation of the analytical variability of urine protein-to-creatinine ratio in cats. Vet Clin Pathol. 2018;47(3):448–457.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23.

    McLeland SM, Cianciolo RE, Duncan CG, Quimby JM. A comparison of biochemical and histopathologic staging in cats with chronic kidney disease. Vet Pathol. 2015;52(3):524–534.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24.

    Reynolds BS, Lefebvre HP. Feline CKD pathophysiology and risk factors—what do we know? J Feline Med Surg. 2013;15:3–14.

  • 25.

    Brown CA, Elliott J, Schmiedt CW, Brown SA. Chronic kidney disease in aged cats: clinical features, morphology, and proposed pathogeneses. Vet Pathol. 2016;53(2):309–326.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26.

    Kumar GK, Kamran CA, Sathyanarayana ML. Gross and histopathological changes in canine chronic kidney disease. J Entomol Zool Stud. 2019;7:1078–1080.

    • Search Google Scholar
    • Export Citation
  • 27.

    Rayhel LH, Quimby JM, Cianciolo RE, Cléroux A, McLeland SM, Franken T. Clinicopathologic and pathologic characteristics of feline proteinuric kidney disease. J Feline Med Surg. 2020;22(12):1219–1229.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28.

    Rossi F, Aresu L, Martini V, et al. Immune-complex glomerulonephritis in cats: a retrospective study based on clinico-pathological data, histopathology and ultrastructural features. BMC Vet Res. 2019;15:303.

    • Search Google Scholar
    • Export Citation

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