Utility of urinary markers in the assessment of renal dysfunction in canine babesiosis

Dagmara Winiarczyk; Łukasz Adaszek; Michał Bartnicki; Beata Abramowicz; Paweł Łyp; Jacek Madany; Stanisław Winiarczyk

doi:10.15654/TPK-160490

Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere, Table of Contents

Tierarztl Prax Ausg K Kleintiere Heimtiere 2017; 45(02): 84-88
DOI: 10.15654/TPK-160490

Original Article

Schattauer GmbH

Utility of urinary markers in the assessment of renal dysfunction in canine babesiosis

Nützlichkeit von Urinmarkern zur Beurteilung von Nierenfunktionsstörungen bei Hunden mit Babesiose

Authors

Dagmara Winiarczyk

¹Department and Clinic of Animal Internal Diseases, Faculty of Veterinary Medicine, University of Life Sciences Lublin, Lublin, Poland
Łukasz Adaszek

²Department of Epizootiology and Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences Lublin, Lublin, Poland
Michał Bartnicki

²Department of Epizootiology and Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences Lublin, Lublin, Poland
Beata Abramowicz

¹Department and Clinic of Animal Internal Diseases, Faculty of Veterinary Medicine, University of Life Sciences Lublin, Lublin, Poland
Paweł Łyp

²Department of Epizootiology and Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences Lublin, Lublin, Poland
Jacek Madany

¹Department and Clinic of Animal Internal Diseases, Faculty of Veterinary Medicine, University of Life Sciences Lublin, Lublin, Poland
Stanisław Winiarczyk

²Department of Epizootiology and Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences Lublin, Lublin, Poland

Abstract

Summary

Objective: Canine babesiosis is a common and clinically significant tick-borne disease caused by haemoprotozoan parasites of the genus Babesia. Acute renal failure is considered to be one of the most prevalent complications of canine babesiosis. This complication leads to a decrease in the glomerular filtration rate and in consequence causes azotemia and uremia. The objective of this study was to assess the localization and extent of renal damage in dogs infected with Babesia canis using an urinary marker for glomerular (urinary immunoglobulin G, uIgG), proximal tubular dysfunction (urinary retinol binding protein, uRBP) and distal tubular dysfunction (urinary Tamm-Horsfal protein, uTHP). Material und methods: In 10 dogs naturally infected with B. canis and 10 healthy control dogs the levels of urinary biomarkers were measured using commercially available ELISA tests. Results: Higher concentrations of uIgG, uRBP and uTHP were found in the urine of all dogs with babesiosis than in those from the control group. This indicates that in the course of the disease, the glomeruli as well as the renal tubules become damaged. Conclusion and clinical relevance: The study results allow a better understanding of the pathogenesis of canine babesiosis. However, in order to fully determine the extent and the nature of the damage to the kidneys of the infected dogs, it is advisable to conduct additional histopathological examinations of these organs.

Zusammenfassung

Gegenstand und Ziel: Die kanine Babesiose ist eine häufig vorkommende und klinisch bedeutsame Krankheit, die durch Zecken übertragen und durch Parasiten der Gattung Babesia hervorgerufen wird. Als eine der häufigsten Komplikationen tritt akutes Nierenversagen auf. Es führt zu einer Abnahme der glomerulären Filtrationsrate und zu Azotämie und Urämie. Ziel der Untersuchungen war, die Lokalisation und das Ausmaß der Nierenschädigung bei Hunden mit Babesiose zu beurteilen. Material und Methoden: Mittels kommerziell erhältlicher ELISA-Tests wurde die Konzentration von Urinmarkern bestimmt, die eine glomeruläre Dysfunktion (Immunglobulin G im Urin, uIgG), eine Dysfunktion im Bereich des proximalen Tubulus (Retinolbindungs protein im Urin, uRBP) bzw. distalen Tubulus (Tamm-Horsfal-Protein im Urin, uTHP) anzeigen. Ergebnisse: Bei allen Hunden mit Babesiose lagen die uRBP- und uTHP-Konzentrationen im Harn deutlich höher als bei den Kontrollhunden. Dies zeigt, dass im Verlauf der Erkrankung eine Schädigung der Glomeruli und der Nierentubuli stattfindet. Schlussfolgerung und klinische Relevanz: Die Ergebnisse der Studie ermöglichen ein besseres Verständnis der Pathogenese der kaninen Babesiose. Zur genaueren Bestimmung von Ausmaß und Art der Nierenschädigung ist jedoch eine histopathologische Untersuchung der Nieren zweckmäßig.

Keywords

Babesia canis - dogs - urinary immunoglobulin G - urinary retinol binding protein - urinary Tamm-Horsfal protein

Schlüsselwörter

Babesia canis - Hund - Immunglobulin G im Urin - Retinolbindungsprotein im Urin - Tamm-Horsfal-Protein im Urin

Full Text

References

References
1 Acton A. Issues in Veterinary Practices and Specialties. 2013 edition. Scholarly Editions. 2013. Atlanta, Georgia: 423-424.
2 Adaszek Ł, Winiarczyk S. Molecular characterization of Babesia canis canis isolates from naturally infected dogs in Poland. Vet Parasitol 2008; 152: 235-241.
3 Adaszek Ł, Winiarczyk S, Skrzypczak M. The clinical course of babesiosis In 76 dogs infected with protozoa parasites Babesia canis canis. Pol J Vet Sci 2009; 12: 81-87.
4 Adaszek Ł, Martinez AC, Winiarczyk S. The factors affecting the distribution of babesiosis in dogs in Poland. Vet Parasitol 2011; 181: 160-165.
5 Adaszek Ł, Górna M, Winiarczyk S. Electrolyte level and blood pH in dogs infected by various 18S RNA strains of Babaesia canis canis on the early stage of babesiosis. Berl Munch Tierarztl Wochenschr 2012; 125: 45-51.
6 Bernard AM, Vyskocil AA, Mahieu P. Assessment of urinary retinol-binding protein as an index of proximal tubular injury. Clin Chem 1987; 33: 775-779.
7 Brkljacić M, Matijatko V, Kis I, Kucer N, Forsek J, Rafaj RB, Grden D, Torti M, Mayer I, Mrljak V. Molecular evidence of natural infection with Babesia canis canis in Croatia. Acta Vet Hung 2010; 58: 39-46.
8 D‘Amico G, Bazzi C. Pathophysiology of proteinuria. Kidney Int 2003; 63: 809-825.
9 Defauw P, Schoeman JP, Smets P, Goddard A, Meyer E, Liebenberg C, Daminet S. Assessment of renal dysfunction using urinary markers in canine babesiosis caused by Babesia rossi. Vet Parasitol 2012; 190: 326-332.
10 Dzięgiel B, Adaszek Ł, Carbonero A, Łyp P, Winiarczyk M, Dębiak P, Winiarczyk S. Detection of canine vector-borne diseases in eastern Poland by ELISA and PCR. Parasitol Res 2016; 115: 1039-1044.
11 El-Achkar TM, Wu XR. Uromodulin in kidney injury: an instigator, bystander, or protector?. Am J Kidney Dis 2012; 59: 452-461.
12 Forterre S, Raila J, Schweigert FJ. Protein profiling of urine from dogs with disease using Protein Chip analysis. J Vet Invest 2004; 16: 271-277.
13 Grauer AM, Neuberger A. The development of a radioimmunoassay for the measurement of urinary Tamm-Horsfall glycoprotein in the presence of sodium dodecyl sulphate. Clin Sci 1973; 44: 163-179.
14 Gray J, Zintl A, Hildebrandt A, Hunfeld KP, Weiss L. Zoonotic babesiosis: Overview of the disease and novel aspects of pathogen identity. Tick and Tick-borne Disease 2010; 1: 3-10.
15 Halos L, Lebert I, Abrial D, Danlois F, Garzik K, Rodes D, Schillmeier M, Ducrot C, Guillot J. Questionnaire-based survey on the distribution and incidence of canine babesiosis in countries of Western Europe. Parasite 2014; 21: 13.
16 Haraldsson B, Nyström J, Deen MW. Properties of the glomerular barrier and mechanisms of proteinuria. Physiol Rev 2008; 88: 451-487.
17 Jacobson LS. The South African form of severe and complicated canine babesiosis: clinical advances 1994–2004. Vet Parasitol 2006; 138: 126-139.
18 Jacobson LS, Clark IA. The pathophysiology of canine babesiosis: new approaches to an old puzzle. J S Afr Vet Assoc 1994; 65: 134-145.
19 Kanals JJ, Hopfer U. Effect of TGF-beta 1 and TNF-alpha on the plasminogen system of rat proximal tubular epithelial cells. J Am Soc Nephrol 1997; 8: 184-192.
20 Kubelová M, Tkadlec E, Bednář M, Roubalová E, Siroký P. West-to-east differences of Babesia canis canis prevalence in Dermacentor reticulatus ticks in Slovakia. Vet Parasitol 2011; 180: 191-196.
21 Lobetti RG, Reyers F. Met-hemoglobinuria in naturally occurring Babesia canis infection. J S Afr Vet Assoc 1996; 67: 88-90.
22 Lynn KL, Marshall RD. Excretion of Tamm-Horsfall glycoprotein in renal disease. Clin Nephrol 1984; 22: 253-257.
23 Maddens BEJ, Daminet S, Demeyere K, Demon D, Smets P, Meyer E. Validation of immunoassays for the candidate renal markers C-reactive protein, immunoglobin G, thromboxane B2 and retinol binding protein in canine urine. Vet Immunol Immunopathol 2010; 134: 259-264.
24 Majláthová V, Majláth I, Víchová B, Gul’ová I, Derdáková M, Sesztáková E, Pet’ko B. Polymerase chain reaction confirmation of Babesia canis canis and Anaplasma phagocytophilum in dogs suspected of babesiosis in Slovakia. Vector Borne Zoonotic Dis 2011; 11: 1447-1451.
25 Mathe A, Dobos-Kovacs M. Histological and ultrastructural studies of renal lesions in Babesia canis infected dogs treated with imidocarb. Acta Vet Hung 2007; 55: 511-523.
26 Matijako V, Torti M, Schetters TP. Canine babesiosis in Europe: how many diseases?. Trends Parasitol 2012; 28: 99-105.
27 McKenzie JK, Patel R, McQueen EG. The excretion rate of Tamm Horsfall urinary mucoprotein in normals and in patients with renal disease. Aust Ann Med 1964; 13: 13-39.
28 Milczak A, Riha T, Abramowicz B, Madej E. Hemostatic disorders during the course of canine babesiosis. Med Weter 2004; 60: 1067-1070.
29 Nabity MB, Lees GE, Cianciolo R, Boggess MM, Steiner JM, Suchodolski JS. Urinary biomarkers of renal disease in dogs with X-linked hereditary nephropathy. J Vet Intern Med 2012; 26: 282-293.
30 Raila J, Neumann U, Schweigert FJ. Immunochemical localization of megalin, retinol-binding protein and Tamm-Horsfall glycoprotein in the kidneys of dogs. Vet Res Commun 2003; 27: 125-135.
31 Smets PMY, Meyer E, Maddes BEJ, Duchateau L, Daminet S. Urinary markers in healthy young and aged dogs and dogs with chronic kidney disease. J Vet Intern Med 2010; 24: 65-72.
32 Solano-Gallego L, Trotta M, Carli E, Carcy B, Caldin M, Furlanello T. Babesia canis canis and Babesia canis vogeli clinicopathological findings and DNA detection by means of PCR-RFLP in blood from Italian dogs suspected of tick-borne disease. Vet Parasitol 2008; 157: 211-221.
33 Thornley C, Dawnay A, Cattel WR. Human Tamm-Horsfall glycoprotein: urinary and plasma levels in normal subjects and patients with renal disease determined by fully validated radioimmunoassay. Clin Sci (Lond) 1985; 68: 529-535.
34 Venkataraman R, Kellum JA. Defining acute renal failure: the RIFLE criteria. J Intensive Care Med 2007; 22: 187-193.
35 Vinge L, Lees GE, Nielsen R. The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney. Nephrol Dial Transplant 2010; 25: 2458-2467.
36 Yalcin A, Cetin M. Electrophoretic separation of urine proteins of healthy dogs and dogs with nephropathy and detection of some urine proteins of dogs using immunoblotting. Revue Med Vet 2004; 155: 104-112.
37 Zahler M, Schein E, Rinder H, Gothe R. Characteristic genotypes discriminate between Babesia canis isolates of differing vector specificity and pathogenicity in dogs. Parasitol Res 1998; 84: 544-548.
38 Zygner W, Rapacka G, Gójska-Zygner O, Długosz E, Wedrychowicz H. Biochemical abnormalities observed in serum of dogs infected with large Babesia in Warsaw (Poland). Pol J Vet Sci 2007; 10: 245-253.
39 Zygner W, Gójska-Zygner O, Bąska P, Długosz E. Increased concentration of serum TNF alpha and its correlations with arterial blood pressure and indices of renal damage in dogs infected with Babesia canis. Parasitol Res 2014; 113: 1499-1503.
40 Zygner W, Gójska-Zygner O, Wesołowska A, Wędrychowicz H. Urinary creatinine to serum creatinine ratio and renal failure index in dogs infected with Babesia canis. Acta Parasitol 2013; 58: 297-303.