Canine babesiosis is a tick-borne protozoan disease caused by parasites of the genus
Hyponatraemia was also observed in dogs infected with
SIADH in humans may result from eutopic or ectopic secretion of ADH, and it has been recognised in neoplastic diseases (
Owing to the facts that babesiosis and malaria are similar diseases, hyponatraemia was noted in both, and SIADH was diagnosed in human malaria, the authors of this study hypothesised that SIADH may also occur in canine babesiosis.
Thirty-six serum, whole blood, and urine samples were collected from dogs of various breeds naturally infected with
Clinical examination (including blood pressure measurement) was performed during the visit before sample collection. Mean arterial pressure was measured using the oscillometric technique with a Cardell 9405 veterinary monitor (Midmark, USA). Serum and urine sodium concentrations were determined by a Rapidchem 744 clinical chemistry analyser (Siemens Healthcare Diagnostics, Germany).
Before determination of urinary sodium concentration, urine samples were centrifuged (2,000 rpm, 5 min) and then supernatant fluid was diluted tenfold in deionised water. Serum and urine concentrations of creatinine and serum urea and glucose content were assayed by an XL 640 clinical chemistry analyser (Erba Mannheim, Germany). Urine specific gravity (USG) was read using a Reichert VET 360 veterinary refractometer (Reichert, USA). These parameters were used to derive effective extracellular fluid (ECF) osmolality (tonicity), calculated osmolality, and the renal failure index. Effective ECF osmolality was calculated according to Wellman
Exclusion criteria were as follows: data supporting the suspicion of hypothyroidism, adrenal disease or renal disease (in group A before infection), and recent use of diuretics. Moreover, all infected dogs with clinical signs such as vomiting, diarrhoea, dehydration, ascites, oedema, and RFI > 2 indicating renal injury were excluded from the study.
Obtained results guided the division of group A into two subgroups: A1, of azotaemic dogs and A2, of non-azotaemic dogs. The results were analysed using the Statistica 13.3 programme (Tibco Software, USA). The Shapiro–Wilk W-test was used for the estimation of normality in the distributions of concentrations of urinary and serum sodium, effective ECF osmolality, urine specific gravity, and mean arterial pressure in groups A and B and subgroups A1 and A2. Depending on the normality of distributions, Spearman’s rank correlation coefficient (other than normal distribution) or Pearson’s correlation coefficient (normal distribution) was used to calculate correlations between MAP and serum and urinary sodium concentrations, USG, serum tonicity, and calculated serum osmolality in groups A and B and subgroups A1 and A2.
Among 36 infected animals (group A), 15 dogs had azotaemia (mean serum creatinine concentration 3.51 ± 1.85 mg/dL and mean serum urea concentration 245.5 ± 121.4 mg/dL), and 21 dogs had no azotaemia (subgroup A2: mean serum creatinine concentration 1.09 ± 0.30 mg/dL and mean serum urea concentration 39.7 ± 7.8 mg/dL). However, seven azotaemic dogs were excluded from the study owing to RFI > 2 indicating renal azotaemia and corroborating clinical signs such as vomiting, diarrhoea and dehydration in these animals. Mean serum creatinine and urea concentrations in subgroup A1 (azotaemic dogs after exclusion of the seven dogs with renal azotaemia) were as follows: mean serum creatinine concentration 2.37 ± 0.42 mg/dL and mean serum urea concentration 165.7 ± 55.2 mg/dL. None of the dogs in this study had signs of hypothyroidism, adrenal or renal disease before the infection, and none of them had been treated with diuretics recently. A PCR assay confirmed infection with
The Shapiro–Wilk W-test for normality in urinary and serum sodium, effective ECF osmolality, calculated osmolality, urine specific gravity, and mean arterial pressure showed a non-normal distribution in USG and MAP in group A and subgroup A2 (Table 1).
Results of the Shapiro–Wilk W-test for normality in groups A and B and subgroups A1 and A2 in the distribution of effective ECF osmolality, calculated osmolality, serum sodium concentration, urinary sodium concentration, urine specific gravity, and mean arterial pressure
Parameter | Group | W | p |
---|---|---|---|
Effective ECF osmolality | A | 0.968 | 0.532 |
B | 0.964 | 0.769 | |
A1 | 0.971 | 0.910 | |
A2 | 0.957 | 0.469 | |
Calculated osmolality | A | 0.954 | 0.243 |
B | 0.984 | 0.989 | |
A1 | 0.891 | 0.239 | |
A2 | 0.944 | 0.263 | |
Serum Na+ | A | 0.966 | 0.465 |
B | 0.959 | 0.690 | |
A1 | 0.947 | 0.681 | |
A2 | 0.958 | 0.486 | |
Urinary Na+ | A | 0.952 | 0.214 |
B | 0.988 | 0.998 | |
A1 | 0.962 | 0.825 | |
A2 | 0.953 | 0.363 | |
USG | A | 0.919 | 0.029* |
B | 0.934 | 0.309 | |
A1 | 0.853 | 0.104 | |
A2 | 0.902 | 0.039* | |
MAP | A | 0.849 | 0.001* |
B | 0.976 | 0.939 | |
A1 | 0.892 | 0.245 | |
A2 | 0.856 | 0.005* |
ECF – extracellular fluid, Serum Na+ – serum sodium concentration, Urinary Na+ – urinary sodium concentration, USG – urine specific gravity, MAP – mean arterial pressure, W – value of W in the Shapiro–Wilk W-test, p – value of p, * – p < 0.05
In groups A and B and subgroup A1, there were no statistically significant correlations between MAP and effective ECF osmolality, calculated osmolality, serum and urinary sodium concentrations, or urine specific gravity. Statistically significant positive correlations were observed between MAP and tonicity, calculated osmolality, and serum sodium concentration in subgroup A2. Statistically significant negative correlations were observed between MAP and urinary sodium concentration and USG (Table 2).
Statistically significant correlations between mean arterial pressure and effective ECF osmolality (Eff. ECF Osm.), calculated osmolality (Calc. Osm.), serum sodium concentration (Serum Na+), urinary sodium concentration (Urinary Na+), and urine specific gravity (USG) in subgroup A2
Correlation | p | ||
---|---|---|---|
MAP | Eff. ECF Osm. | 0.50 | 0.021* |
Calc. Osm. | 0.50 | 0.020* | |
Serum Na+ | 0.49 | 0.021* | |
Urinary Na+ | −0.52 | 0.015* | |
USG | −0.46 | 0.031* |
MAP – mean arterial pressure,
In three dogs from subgroup A2, serum tonicity and calculated serum osmolality were below 275 mOsm/kg, and serum sodium concentration was below the reference interval; these dogs had high urine specific gravity and high urinary sodium concentration (Table 3). In these dogs, SIADH was diagnosed.
Effective extracellular fluid osmolality, calculated serum osmolality serum and urinary sodium concentration, urine specific gravity, and mean arterial pressure in three non-azotaemic dogs (from subgroup A2) infected with
Dog no. | Eff. ECF Osm. |
Calc. Osm. |
Serum Na+ |
Urinary Na+ |
USG | MAP (mmHg) |
---|---|---|---|---|---|---|
1 | 255.5 | 259.8 | 124.8 | 122.9 | 1.052 | 93 |
2 | 266.5 | 272.0 | 130.7 | 136.0 | 1.060 | 69 |
3 | 249.8 | 254.5 | 122.4 | 133.7 | 1.055 | 85 |
Abbreviations as in Table 2
This study is the first in which SIADH was recognised in canine babesiosis. Three dogs had hyponatraemia with serum tonicity and calculated serum osmolality lower than 275 mOsm/kg, high urinary sodium concentration, and high USG, which is strongly correlated with urine osmolality (3). These dogs had no clinical signs of hypovolaemia. An RFI lower than 2 and lack of azotaemia in these dogs indicated normal renal function. Before infection, these dogs were healthy and had no signs of hypothyroidism or hypocorticism. Changes of cortisol levels, ACTH, thyroid hormones, and TSH were observed in canine babesiosis, and therefore concentrations of these hormones were not determined in this study (27, 38). Before infection, the dogs had not been treated recently with any drugs (including diuretics). Thus, in the authors’ opinion these three dogs with hyponatraemia, hypotonicity, and hypoosmolality had SIADH. This result confirms observations from the previous studies on electrolyte disorders in canine babesiosis where hyponatraemia was observed in dogs infected with
Fluid restriction is also useful in recognition of SIADH (11). However, the owners of these dogs did not heed this recommendation. The authors of this study did not determine urine osmolality. However, as mentioned above, Ayoub
In humans, there are three etiological classes of SIADH: endogenous, exogenous, and idiopathic. The exogenous class has aetiology in administration of vasopressin or its analogues, and the endogenous class includes four aetiologies: hypothalamic production of ADH, ectopic secretion of ADH (in neoplastic diseases), a potentiating ADH effect of some drugs, and nephrogenic syndrome of inappropriate antidiuresis (11). It seems probable that the cause of SIADH in canine babesiosis is increased hypothalamic production of vasopressin. This study showed correlations between MAP and serum tonicity, calculated serum osmolality, serum and urinary sodium concentrations, and USG, and it seems probable that increased production of vasopressin may be a response to hypotension which was observed in previous studies on canine babesiosis caused by infection with
According to Vantyghem
Hyponatraemia and SIADH in canine babesiosis seem contradictory to the hyperaldosteronism recognised in a previous study in dogs infected with
One limitation of this study is the lack of an osmometer for determination of serum and urinary osmolality. However, serum osmolality and tonicity were calculated using results of serum sodium, glucose, and urea concentrations, and calculated serum osmolality should be very similar to the osmolality which would have been determined by osmometer. Moreover, as previously noted USG is strongly correlated with urine osmolality in dogs (3, 10). Another limitation of the study was the non-adherence by the owners of the dogs to the advice to restrict fluids, which could have led to correction of hyponatraemia (10). This was predicated on the mildness of the hyponatraemia set against their fear of azotaemia and renal complications.
In conclusion, there is a high probability that SIADH develops in non-azotaemic dogs with babesiosis. It is probably associated with lower blood pressure in infected dogs, and hypothalamic production of vasopressin is a possible response to hypotension in canine babesiosis. Thus, it seems that in fact it may be appropriate ADH secretion in dogs with parasites of the genus