Relationship between urinary neutrophil gelatinase-associated lipocalin and selected biochemical and urinary parameters in dogs naturally infected with Leishmania infantum

Abstract

Background and aim: Leishmania infantum infection in dogs has several clinical manifestations. Glomerulonephritis, caused by circulating immune complexes, may cause proteinuria and progress to kidney failure, which is the primary cause of death in dogs with canine leishmaniasis (CanL). Renal proteinuria can be monitored in dogs with CanL for the early detection of renal involvement. Neutrophil gelatinase-associated lipocalin (NGAL) is a neutrophil-derived protein that is filtered by glomeruli and reabsorbed by proximal tubular cells. Urinary NGAL (uNGAL) is a sensitive marker of acute and chronic kidney disease in dogs. This study aimed to evaluate uNGAL concentrations in dogs naturally affected by CanL, to determine whether uNGAL concentration differs depending on the stage of disease based on the LeishVet and International Renal Interest Society (IRIS) classification systems, to compare uNGAL concentration with selected urinary and biochemical parameters related to kidney function, and to assess the clinicopathological status of dogs affected by CanL.

Materials and methods: We assessed uNGAL concentrations in 37 privately owned dogs naturally affected by CanL, in which urinary tract infections were excluded based on negative urine culture. No dog exhibited clinical signs related to impaired renal function. uNGAL concentration evaluated in dogs affected by CanL was compared to the one previously analyzed in the control group. Furthermore, the uNGAL concentration was compared between leishmaniasis dogs with biochemical and urinary parameters inside or outside the normal range and between dogs with different clinical stages of leishmaniasis based on the LeishVet clinical staging guidelines and IRIS classification.

Results: The median uNGAL concentration in affected dogs was 50.2 ng/mL, which was significantly higher than that in healthy dogs (9.74 ng/mL [p = 0.0025]). uNGAL concentration was significantly higher in proteinuric leishmaniosis dogs than in non-proteinuric leishmaniosis dogs (p = 0.0001). Dogs classified as LeishVet clinical stage III had a higher mean uNGAL concentration than those classified as stage II (p = 0.0001) and median uNGAL concentration was statistically higher in dogs classified as IRIS stage 1 than in dogs affected by CanL with no clinical and pathological signs of renal disease. The amount of proteinuria and urinary sediment hyaline cast per high-power field of the microscope and total serum protein concentrations were significantly correlated with uNGAL concentration.

Conclusion: To the best of our knowledge, only a few studies have measured uNGAL in dogs naturally affected by CanL. Although limited by the small number of cases, this study highlighted a significant increase in uNGAL levels in affected dogs compared with healthy dogs and confirmed the correlation between proteinuria and urinary excretion of uNGAL in dogs with leishmaniasis. This suggests that uNGAL can be used as a marker of kidney damage in dogs affected by CanL.

Keywords: canine; canine leishmaniasis; hematological parameters; proteinuria; urinary neutrophil gelatinase-associated lipocalin; urinary protein-to-creatinine.

Figure-1

Graphic representation of Spearman correlation (a) between urinary neutrophil gelatinase-associated lipocalin (uNGAL) and urinary protein/creatinine and (b) between uNGAL and serum total protein concentrations.

Figure-2

Box plot showing the difference between urinary neutrophil gelatinase-associated lipocalin concentration in dogs with (a) urinary protein/creatinine values above and below 0.5, (b) total protein concentration above and below 8 g/dl, and (c) hyaline cast high power field (hpf) mean number above and below 2 in urinary sediment. Data are presented as boxes and whiskers. Each box includes 25 and 75 interquartiles, whereas the line inside the box represents the median and the whiskers represent the minimum and maximum values.