INTRODUCTION – In human medicine, diabetes mellitus (DM), hypertension,
proteinuria and nephropathy are often associated although it is still not clear whether
hypertension is the consequence or the cause of nephropathy and albuminuria.
Microalbuminuria, in humans, is an early and sensitive marker which permits timely
and effective therapy in the early phase of renal damage. Conversely, in dogs, these
relationships were not fully investigated, even though hypertension has been
associated with many diseases (Bodey and Michell, 1996). In a previous study, 20%
of diabetic dogs were found proteinuric based on a U:P/C > 1 and 46% were
hypertensive; this latter finding is similar to the prevalence of hypertension in diabetic
people (40-80%) (Struble et al., 1998). In the same canine study, hypertension was
also positively correlated with the duration of the disease, as is the case in human
beings. Hypertension was also found to be a common complication of
hypercortisolism (HC) in dogs, with a prevalence which varies from 50 (Goy-Thollot
et al., 2002) to 80% (Danese and Aron, 1994).The aim of our study was to evaluate
the urinary albumin to creatinine ratio (U:A/C) in dogs affected by Diabetes Mellitus
and HC in order to ascertain if, as in human beings, it could represent an early and
more sensitive marker of renal damage than U:P/C. Furthermore, the relationship
between proteinuria and hypertension in DM and HC was also investigated.
MATERIALS AND METHODS – Twenty dogs with DM, 14 with HC and 21
healthy dogs (control group) were included in the prospective case-control study.
Inclusion criteria were hyperglycaemia, glicosuria and serum fructosamine above the
reference range for DM dogs and a positive ACTH stimulation test and/or low-dose
dexamethasone test and consistent findings of HC on abdominal ultrasonography in
HC dogs. Dogs were excluded if affected by urinary tract infections and if the serum
creatinine or urea values were above the reference range. At the moment of inclusion,
an appropriate therapy had already been instituted less than 1 month earlier in 12
diabetic dogs. The control dogs were considered healthy based on clinical exam and
clinicopathological findings. All dogs underwent urine sample collection by
cystocentesis and systemic blood pressure measurement by means of either an
oscillometric device (BP-88 Next, Colin Corporation, Japan) or by Doppler ultrasonic
traducer (Minidop ES-100VX, Hadeco, Japan). The choice of method depended on the
dog’s body weight: Doppler ultrasonography was employed in dogs < 20 kg of body
weight and the oscillometric method in the other subjects. Dogs were considered
hypertensive whenever systemic blood pressure was found ≥ 160 mmHg. The urine
was assayed for U:P/C and U:A/C (Gentilini et al., 2005). The data between groups
were compared using the Mann-Whitney U test. The reference ranges for U:P/C and
U:A/C had already been established by our laboratory as 0.6 and 0.05, respectively.
U:P/C and U:A/C findings were correlated to systemic blood pressure and Spearman
R correlation coefficients were calculated. In all cases, p < 0.05 was considered
statistically significant.
RESULTS – The mean ± sd urinary albumin concentration in the three groups was
1.79 mg/dl ± 2.18; 20.02 mg/dl ± 43.25; 52.02 mg/dl ± 98.27, in healthy, diabetic and
hypercortisolemic dogs, respectively. The urine albumin concentration differed
significantly between healthy and diabetic dogs (p = 0.008) and between healthy and
HC dogs (p = 0.011). U:A/C values ranged from 0.00 to 0.34 (mean ± sd 0.02 ± 0.07),
0.00 to 6.72 (mean ± sd 0.62 ± 1.52) and 0.00 to 5.52 (mean ± sd 1.27 ± 1.70) in the
control, DM and HC groups, respectively; U:P/C values ranged from 0.1 to 0.6 (mean
± sd 0.17 ± 0.15) 0.1 to 6.6 (mean ± sd 0.93 ± 1.15) and 0.2 to 7.1 (mean ± sd 1.90 ±
2.11) in the control, DM and HC groups, respectively. In diabetic dogs, U:A/C was
above the reference range in 11 out of 20 dogs (55%). Among these, 5/20 (25%)
showed an increase only in the U:A/C ratio while, in 6/20 (30%), both the U:P/C and
the U:A/C were abnormal. Among the latter, 4 dogs had already undergone therapy.
In subjects affected with HC, U:P/C and U:A/C were both increased in 10/14 (71%)
while in 2/14 (14%) only U:A/C was above the reference range. Overall, by
comparing U:P/C and U:A/C in the various groups, a significant increase in protein
excretion in disease-affected animals compared to healthy dogs was found. Blood
pressure (BP) in diabetic subjects ranged from 88 to 203 mmHg (mean ± sd 143 ± 33
mmHg) and 7/20 (35%) dogs were found to be hypertensive. In HC dogs, BP ranged
from 116 to 200 mmHg (mean ± sd 167 ± 26 mmHg) and 9/14 (64%) dogs were
hypertensive. Blood pressure and proteinuria were not significantly correlated.
Furthermore, in the DM group, U:P/C and U:A/C were both increased in 3
hypertensive dogs and 2 normotensive dogs while the only increase of U:A/C was
observed in 2 hypertensive and 3 normotensive dogs. In the HC group, the U:P/C and
the U:A/C were both increased in 6 hypertensive and 2 normotensive dogs; the U:A/C
was the sole increased parameter in 1 hypertensive dog and in 1 dog with normal
pressure.
DISCUSSION AND CONCLUSION- The findings of this study suggest that, in
dogs affected by DM and HC, an increase in U:P/C, U:A/C and systemic hypertension
is frequently present. Remarkably, some dogs affected by both DM and HC showed
an U:A/C but not U:P/C above the reference range. In diabetic dogs, albuminuria was
observed in 25% of the subjects, suggesting the possibility that this parameter could
be employed for detecting renal damage at an early phase when common
semiquantiative tests and even U:P/C fall inside the reference range. In HC dogs, a
higher number of subjects with overt proteinuria was found while only 14% presented
an increase only in the U:A/C. This fact, associated with a greater number of
hypertensive dogs having HC rather than DM, could suggest a greater influence on
renal function by the mechanisms involved in hypertension secondary to
hypercortisolemia. Furthermore, it is possible that, in HC dogs, the diagnosis was
more delayed than in DM dogs. However, the lack of a statistically significant
correlation between hypertension and increased protein excretion as well as the
apparently random distribution of proteinuric subjects in normotensive and
hypertensive cases, imply that other factors besides hypertension are involved in
causing proteinuria. Longitudinal studies are needed to further investigate the
relationship between hypertension and proteinuria.
| Identifer | oai:union.ndltd.org:unibo.it/oai:amsdottorato.cib.unibo.it:1138 |
| Date | 11 April 2008 |
| Creators | Mazzi, Antonella <1972> |
| Contributors | Famigli Bergamini, Paolo |
| Publisher | Alma Mater Studiorum - Università di Bologna |
| Source Sets | Università di Bologna |
| Language | Italian |
| Detected Language | English |
| Type | Doctoral Thesis, PeerReviewed |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess |
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