Etude prospective des caractéristiques hématologiques, biochimiques et urinaires du Dogue de Bordeaux: Une race prédisposée à une glomérulopathie familiale

Doctoral thesis (2013)

Dogue de Bordeaux (DDB) dogs are predisposed to a juvenile glomerulonephropathy (JGN), usually leading to an end-stage chronic kidney disease (CKD), mostly before 2 years of age. Since its first ... [more ▼]

Dogue de Bordeaux (DDB) dogs are predisposed to a juvenile glomerulonephropathy (JGN), usually leading to an end-stage chronic kidney disease (CKD), mostly before 2 years of age. Since its first description a few years ago, the number of DDB dogs diagnosed with JGN has drastically increased in Europe. Furthermore, some DDB dogs might develop clinical signs far later than initially thought. As the mode of inheritance of this condition has not yet been elucidated, an early diagnosis of JGN is of central importance for breeders and owners. To ease screening of affected dogs, we first wanted to improve our knowledge of this ancient French breed by describing characteristics of healthy DDB dogs. Given available information, we indeed suspected that some biological specificity existed in this breed, which could affect diagnostic processes and lead to erroneous clinical decisions. We thus determined, in a first study, breed-specific biochemical and hematological reference intervals (RI). For most of the 29 measured biochemical analytes, using the manufacturer’s generic canine RI would not have had a major clinical impact, however breed-specific RI established for 6 of them were relevantly different. Limits of the RI for total proteins, total cholesterol, aspartate aminotransferase, alanine aminotransferase and lipase were higher, while they were markedly lower for total thyroxin. Among the 25 hematological RI that were determined and compared with generic canine RI established in the same laboratory, only those of some red blood cells and platelet indices were sufficiently different to have a significant impact on clinical decision. Most red blood cells indices had higher, whereas most platelet indices had lower RI. As we also hypothesized that some apparently healthy adult DDB could suffer from JGN, we decided to look, in a second study, for the biological abnormalities that were previously described in association with the disease. We thus recruited a large cohort of adult DDB and found that proteinuria (urine protein-to-creatinine ratio (UPC) > 0.5) was present in 33%, and proteinuric CKD in 2% of the dogs. When assessed by UPC, proteinuria increased with age and was associated with changes in several biological variables. Urine specific gravity, plasma albumin and total calcium decreased, whereas cholesterol, fibrinogen and thyroid-stimulating hormone increased with UPC. Furthermore, changes in total renal volume, evaluated by ultrasound, were also described to be affected by magnitude of proteinuria. Having a UPC>0.5 increased the probability of observing urinary granular casts by an odds-ratio of 4. Amplitude of biological variations observed in this study was however generally moderate. Finally, to investigate if proteinuric DDB could be suffering from a glomerular disease related to the JGN, we attempted in a third study to characterize the nature of their proteinuria. For that purpose, we used urinary proteins electrophoresis and specific tubular (retinol binding protein (uRPB) and N-acetyl-β-D-glucosaminidase (uNAG) enzyme) and glomerular (albumin (uAlb) and immunoglobulins G (uIgG)) urinary markers. One hundred and two DDB, including 2 dogs with proteinuric CKD, were retrospectively recruited for this study, irrespective of UPC values, to facilitate comparison. Final interpretations of urine proteins electrophoresis attributed a “normal” pattern to 39 dogs, a tubular pattern to 9 of them, a glomerular pattern to 38, and a mixed pattern to 16. Most of these results were highly correlated to UPC values. However, tubular and mixed patterns were only attributed to entire male dogs because of the presence of an isolated 25kDa band, which might be due to urinary contamination by seminal proteins. When results for urinary markers were compared to values obtained in non proteinuric (UPC≤0.2) DDB dogs, 37% of the borderline proteinuric dogs (0.2≤UPC<0.5) had all four markers within reference limits. On the other hand, all proteinuric DDB dogs had elevated ratios of uAlb and uIgG when their concentrations were related to urinary creatinine (/c). Only 53% of them had an elevated uRBP/c and 35% an elevated uNAG/c, which corresponded to the dogs with highest UPC values. Results of this last study support the hypothesis that proteinuric DDB dogs have a glomerular disease which is likely related to JGN. Additionally, sensitivity, specificity, positive and negative likelihood ratio of electrophoresis to identify dogs with elevated uAlb/c were 94%, 92%, 11.85 and 0.07, in that order. These indices were respectively 90%, 74%, 3.43 and 0.13, to identify DDB dogs with abnormally elevated uIgG/c. [less ▲]

Familial glomerulopathy in seven French Mastiff dogs.

in Proceedings of the 18th Annual Congress of the ECVIM-CA (2008)