Chronic glucocorticoid excess and impaired osmoregulation of vasopressin release in dogs with hepatic encephalopathy.

Chronic liver disease may be accompanied by disturbed sodium and water homeostasis. There is usually sodium retention and ascites. However, spontaneous natriuresis has also been reported in humans and experimental animals with liver cirrhosis. Chronic hypercortisolism, which may occur in dogs with advanced liver disease, is known to induce the inhibition of the osmostimulation of vasopressin (AVP) release. We have therefore investigated the osmoregulation of AVP release in 11 dogs with chronic hypercortisolism associated with advanced liver dysfunction and hepatic encepahlopathy and in 10 control dogs. Basal pituitary-adrenocortical activity was investigated by measuring the concentration in multiple plasma samples of adrenocorticotropin (ACTH), alpha-melanocyte-stimulating hormone (MSH), and cortisol and the cortisol:creatinine ratio in 24-hr urine. Urine specific gravity was also measured. The feedback regulation of the system was investigated by measuring these hormones in plasma after an intravenous (iv) injection of 0.01 mg/kg of dexamethasone. The osmoregulation of the release of AVP was investigated by the intravenous infusion of a 20% NaCl solution at a flow rate of 0.03 ml/kg for 2 hr and the measurement of AVP in plasma sampled at 20-min intervals. The AVP release was analyzed in terms of the threshold osmolality at which it commenced and the sensitivity, which reflects the magnitude of the response. All dogs had highly increased urinary cortisol:creatinine ratios, ranging from 21 to 210 x 10(-6) (normally < 10 x 10(-6)). The mean basal plasma concentrations of the three pituitary-adrenocortical hormones were significantly increased. ACTH values were 35 to 146 ng/l (normally, 14 to 68), MSH values were 26 to 118 ng/l (normally, 10 to 36), and cortisol values were 88 to 194 nmol/l (normally, 23 to 112). The feedback inhibition of the secretion of ACTH and cortisol in response to dexamethasone was unaffected. Urine specific gravity was significantly decreased. The regulation of AVP release was found to be abnormal in all dogs with hepatic encephalopathy. The osmotic threshold at which the release of AVP was induced was abnormally high in seven of the dogs with liver disease and in the normal range in one. It could not be determined in three dogs. The sensitivity of AVP release in response to increasing plasma hypertonicity was normal in two dogs and decreased in nine. In three dogs, there was no increase in AVP release. None of the dogs had normal values for both the sensitivity and the threshold.(ABSTRACT TRUNCATED AT 400 WORDS)

Proteinuria associated with glomerulosclerosis and glomerular collagen formation in three Newfoundland dog littermates.

Three dogs out of a litter of eight Newfoundland dogs developed a progressive fatal glomerulopathy. The affected dogs were a 2-month-old male, a 2.5-month-old female, and a 1-year-old male. The disease in all three animals was characterized by growth retardation, anorexia, proteinuria (14-16 g/liter), hypoalbuminemia (15-21 g/liter, elevated plasma urea (13-28 mmol/liter), and creatinine (83-296 mumol/liter) concentrations. Because of a bad prognosis the dogs were euthanatized. On postmortem examination, the animals had enlarged, slightly pale kidneys, which revealed glomerulosclerosis and glomerulofibrosis on histologic and electron microscopic examination. The lesions consisted of subendothelial and mesangial collagen fibrils and an increase of mesangial matrix. The fibrosis may result from endothelial or mesangial collagen formation as the manifestation of a metabolic disease.

Osmoregulation of systemic vasopressin release during long-term glucocorticoid excess: a study in dogs with hyperadrenocorticism.

In 9 dogs with pituitary-dependent hyperadrenocorticism and in 6 dogs with hyperfunctioning adrenocortical tumours, the osmoregulation of arginine vasopressin (AVP) release was investigated by iv infusion of 20% NaCl for 2 h at a rate of 0.03 ml per kg body weight. The responses were analysed in terms of sensitivity and threshold of the osmoregulation of AVP secretion. The sensitivity was normal in 6 dogs and lowered in 9. In 4 of the latter dogs there was complete absence of a response to hypertonicity. The osmotic threshold of AVP release was raised in 9 dogs and normal in 2 dogs, whereas in the four dogs without any response the term threshold was not applicable. The results were not different for dogs with pituitary-dependent hyperadrenocorticism and dogs with hyperfunctioning adrenocortical tumour. It is concluded that corticosteroid excess per se induces a marked impairment of the osmoregulation of AVP secretion. The loss of reactivity of the osmoreceptor system may contribute to the corticosteroid-induced polyuria, which is also the result of resistance to AVP in the kidney.

Persistent polyuria in two dogs following adrenocorticolysis for pituitary-dependent hyperadrenocorticism.

In two dogs with pituitary-dependent hyperadrenocorticism, adrenocorticolysis with o.p'-DDD led to the disappearance of the signs and symptoms except for the polyuria. After a modified water-deprivation test the osmoregulation of vasopressin release was studied by hypertonic saline infusion. In both dogs the hypertonicity, thus induced, resulted in very minimal responses of the vasopressin secretion.

Effect of arginine vasopressin on urine formation and plasma atrial natriuretic peptide level in conscious dogs.

We investigated the relationship between plasma arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) levels and urine formation in conscious dogs. The rate of urine production and urinary electrolyte excretion were determined following infusion of high doses of AVP to dogs in different volume states. Water deprivation for 24 h induced an antidiuresis while the plasma osmolality, plasma AVP and plasma ANP remained at physiological levels. Subsequent i.v. administration of AVP did not alter the production of urine. Oral water loading (20 ml/kg body weight) induced low plasma AVP levels (1.3 +/- 0.5 pg/ml, mean +/- S.E.M.). Following AVP administration to the water-loaded group, the urine production rate decreased significantly from baseline while the osmolality of the urine increased significantly. Plasma ANP levels did not differ significantly between the two experimental groups, and did not change following i.v. administration of AVP. The results show that, in conscious dogs, (1) the production of a small volume of highly concentrated urine can occur with plasma AVP levels of below 5 pg/ml, (2) 24 h of dehydration induces an antidiuresis while plasma peptides, as well as the different biochemical variables, remain within normal limits, (3) increased plasma AVP levels do not induce a change in plasma ANP levels under these experimental conditions, (4) infusion of AVP induces a significantly increased K+ excretion but only in overhydrated animals.

[Familial nephropathy in cocker spaniels]. / Zur familiären Nephropathie der Cockerspaniel.

In 21 normal dogs of different breeds and ages the number of nephrons was calculated from paraffin sections in comparison with a maceration method. With these methods the number of glomeruli x 1000 per kidney appeared to be 502 +/- 213 and 515 +/- 230 respectively. The histological method appeared to be acceptable for the determination of the number of glomeruli in incomplete kidneys. The examined Cocker Spaniels consisted of 5 animals without renal problems for control and 21 animals with nephropathy: 12 of 1-2 years, 6 of 4-6 years and 3 of 9-10 years old dogs. As indication for the present number of nephrons the glomeruli were counted in bands of whole cortex with a width of 1 mm. The number of glomeruli per band of cortex in the nephropathic Cocker Spaniels (15.0 +/- 3.0) was not drastic lower than those of the normal Cockers (20.8 +/- 2.5) and of 7 normal adult dogs of different breeds (17.2 +/- 2.2). On pathological examination the nephropathic kidneys showed a membranoproliferative-sclerosing glomerulonephritis with extra-capillary reaction leading to glomerular obsolescence. The animals showed evident proteinuria and final renal insufficiency. It was concluded that the pathogenesis of the familial nephropathy in this breed will not be caused by cortical hypoplasia, but by a primary glomerulopathy.

Inappropriate vasopressin secretion in two dogs.

Two dogs with hyponatremia due to inappropriate arginine vasopressin (AVP) secretion are described. Threshold and sensitivity of AVP secretion were investigated by increasing plasma osmolality with hypertonic saline infusion. In one dog, osmoregulation of AVP secretion occurred at normal sensitivity but at a low threshold. The other dog had a relatively high plasma AVP concentration under (resting) hypotonic conditions with an otherwise normal response to increasing plasma tonicity. In the absence of evidence for associated disease, it is suggested that both dogs have an idiopathic form of the syndrome of inappropriate AVP secretion.

Proteinuria in the dog: a pathomorphological study of 51 proteinuric dogs.

Renal cortical biopsies of 51 dogs with spontaneous proteinuria were examined by histology, electron microscopy and immunofluorescence. Glomerular lesions were classified in four groups: mesangioproliferative, membranoproliferative and membranous glomerulonephritis and amyloidosis. The glomerular and the tubulointerstitial lesions were graded, using a semiquantitative system. The results were used for the calculation of correlation coefficients between several parameters. A positive correlation was found between the severity of glomerular and tubulointerstitial lesions. Fibrin detection by immunofluorescence and histochemical methods appeared not to be correlated. The presence of electron dense deposits correlated only with the fluorescence for IgG and C3. Fluorescence for IgA and IgM was frequently observed in cases with or without dense deposits.

The use of arginine vasopressin measurements in the polyuric dog.

The direct measurements of AVP during water deprivation and salt loading demonstrate the inability of the direct water deprivation test to distinguish accurately between several forms of polyuria. Polyuria and polydipsia are commonly formed disorders in the dog and can be caused by osmotic diuresis; deficient release of anti-diuretic hormone-arginine vasopressin (AVP); a decreased renal response to AVP; excessive water intake. The differentiation between these forms often requires a water deprivation test followed by administration of vasopressin. The latter test is an indirect one and relies upon changes in urinary concentration as index of vasopressin function. With this it is usually possible to differentiate total neurogenic diabetes insipidus and total nephrogenic diabetes insipidus. However, several dipsogenic forms and partial diabetes insipidus forms are still very difficult to distinguish from each other and only the direct measurement of plasma AVP (PAVP) can give conclusive information. The role of AVP in osmoregulation was investigated by measuring plasma osmolality (Posm) and PAVP during; hypertonic saline infusions; water deprivation in both healthy experimental dogs and in dogs with polyuria.

Proteinuria in the dog: a clinicopathological study in 51 proteinuric dogs.

In 51 dogs with predominantly massive urinary protein loss, the daily loss was quantified and glomerular and tubulointerstitial lesions from renal biopsies were characterised and graded using histology, immune fluorescence and electron microscopy. The highest median daily urinary protein loss occurred in dogs with membranous glomerulonephritis (median 380 mg kg-1 d-1) and renal amyloidosis (median 257 mg kg-1 d-1). Although in nine febrile dogs the urinary protein loss was transient, both glomerular and tubular lesions were diagnosed in five and seven of these dogs, respectively. The pattern of urinary proteins was determined using sodium dodecyl-sulphate polyacrylamide gel electrophoresis. The albumin fractional clearance (FC) was raised in 46 dogs, whereas the FCS of the low molecular weight (MW) protein fraction (MW less than 66,000) and high molecular weight protein fraction (MW more than 66,000) were raised in 42 and 28 dogs, respectively. Both the high molecular weight protein FC and albumin FC significantly correlated to the grade of glomerular lesions, whereas the low molecular weight protein FC only moderately significantly correlated to the grade of tubular lesions. The selectivity index, calculated as (formula; see text) did not differentiate between the various forms of glomerulopathies. The urinary lysozyme concentration was significantly correlated to the grade of tubular lesions. It is concluded that although quantitative and qualitative measurements of urinary proteins can provide additional clinical information, they do not have a reliable predictive value and histopathological examination of renal tissue is still necessary for the final diagnosis.

Cystourethroscopy in the dog.

The cystourethroscopic examination with cold light cystoscopes forms an essential part of a complete urological examination and is useful for diagnostic as well as surgical procedures. The fast and non-invasive character of the procedure limits the inconvenience to the patient. With the rigid non-flexible scope its use is, however, limited to female dogs, unless in the male dog a urethro(s)tomy is performed.

Assessment of renal blood flow in dogs: analysis of 131I-hippuran blood clearance in healthy dogs and in dogs with proteinuria.

In 30 clinically healthy dogs (weights 7.5 to 57 kg) and in 41 proteinuric dogs the 131I-hippuran blood disappearance curve after single injection was determined (0 to 90 minutes), described by a bi-exponential function and analysed according to a two compartment model. The dependence of the blood clearance (C), representing an effective renal blood flow, on the bodyweight (W) (kg) could be described with both a linear function (C = 61 + 13.2 W ml min-1) and a power function (C = 30.56 W0.79 ml min-1) in the healthy dogs. The results of the regression between blood clearance and bodyweight were reproducible (r = 0.92, n = 10 residual error 12 per cent, P less than 0.01).

Urinary protein loss in the dog: nephrological study of 29 dogs without signs of renal disease.

In 29 dogs without any sign of renal disease, the total daily urinary protein loss was measured and related to renal morphology. The daily urinary protein loss was less than 10 mg/kg bodyweight in most dogs (24 out of 29). The median value of the protein loss in dogs with and without lesions differed significantly, as well as the median values of the ages of dogs with and without lesions. Polyacrylamide gel electrophoresis of urinary protein revealed the presence of albumin, high molecular weight and low molecular weight proteins. With immunofluorescence, especially, the presence of IgA (21 out of 28) and IgM (17 out of 28) was shown. In 12 out of 14 dogs with glomerular lesions IgA deposits were demonstrated (graded as +/- in two dogs and as + in 10 dogs), whereas in nine out of 14 dogs without glomerular lesions IgA deposits were demonstrated (graded as +/- in four dogs and as + in five dogs). The presence of IgA was significantly related to the presence of glomerular lesions (P less than 0.05). Fibrinogen degradation products were not detectable in urine from 15 of 23 dogs.

[Urological complications following ovariohysterectomy in dogs (author's transl)]. / Urologische complicaties na ovario-hysterectomie bij de hond.

Of the total number of dogs submitted with complications following ovariohysterectomy (109), eighteen were found to show pathological changes of the kidney and/or excretory urinary ducts. Eleven patients showed specific urological problems such as pollakiuria (7 cases), urinary incontinence (6 cases) and haematuria (5 cases). When there was a reason for doing so, specific urological studies were undertaken, including excretion urography in seven cases, in addition to physical and laboratory studies. During laparotomy and/or post-mortem examination (the latter being carried out in eight dogs), the following adhesions were observed, among others: the cervix stump adhered to the bladder in nine cases, to the right ureter in five and to the left ureter in three cases. Either granulomas at the ovarian stump (one case) or cervix stump (five cases) or actual ligation of the ureters in the ovarian (two cases) or cervix stump ligature (three cases) caused partial or total obstruction, which occasionally resulted in hydro-, pyo- or haemonephrosis, atrophy of the kidney or focal nephritis.

Dubious effect of dimethylsulphoxide (DMSO) therapy on amyloid deposits and amyloidosis.

Data from the literature on DMSO therapy for amyloidosis in laboratory animals and man are reviewed and found to be inconclusive. In hamsters with casein-induced amyloidosis, as well as in dogs with spontaneous amyloidosis, therapeutic experiments with DMSO were performed. In these investigations no effect of DMSO on amyloid and amyloidosis was found.

Assessment of glomerular filtration rate in normal dog: analysis of the 51Cr-EDTA clearance and its relation to several endogenous parameters of glomerular filtration.

In 34 normal dogs the 51Cr-EDTA plasma clearance (C) according to the single injection technique was determined. The biexponential plasma disappearance curves were analysed according to a two compartment model. The results were compared with the plasma levels of creatinine and urea and with the endogenous creatinine clearance. In particular the dependence on body-weight (W) (range 8 to 57 kg) was established for several parameters. The dependence of C (ml per minute) on W (kg) could be described with both a linear function (C = 10 + 2.5 W) and a power function (C = 4.2 W0.88). The total distribution volume was equivalent to 19.6 per cent of W (range 12.1 to 33.5 per cent) whereas the rate constant lambda 0 (mean value 0.020 per minute, range 0.0115 to 0.0266 per minute) characterising the renal excretion did not depend on W. Good reproducibility (r = 0.92) of the C values was found in a test involving 13 dogs.

Assessment of glomerular filtration rate in dogs with renal insufficiency: analysis of the 51Cr-EDTA clearance and its relation to the plasma concentrations of urea and creatinine.

The glomerular filtration rate (GFR) was determined with the single injection 51Cr-EDTA clearance in 48 dogs with renal disease and the results were compared with the plasma Creatinine (PC) and plasma urea (PU) levels. The superiority of PC values over PU values for the assessment of the GFR is represented by the power functions PC = 78.2 CR(-0.67) mmol per litre and PU = 10.3 Cr(-0.52) mmol per litre, in which Cr is the relative glomerular filtration rate. The higher correlation between PC and Cr (r = 0.834) than between PU and Cr (r = 0.693) also demonstrates this superiority. An extended two compartment analysis of the 51Cr-EDTA plasma disappearance curve is not essential for diagnostic purposes.

Urovagina associated with female pseudohermaphroditism in four bitches from one litter.

Four littermates with pseudo-hermaphroditismus ovarialis are described. Each had passive urinary incontinence caused by a urovagina. Clinical and radiographic examination and the surgical treatment are described. Results, follow-up and etiology are discussed.

Quantitation of lysozyme in the urine of the dog for the diagnosis of proximal tubular damage in renal disease.

The serum and urine LZM levels were determined with the lysoplate assay in 26 normal experimental dogs and in 21 dogs with various renal diseases. In the dogs with decreased glomerular filtration the serum LZM levels were higher than in normal dogs (less than or equal to 1.3 mg/l). No LZM could be demonstrated in the urine of normal dogs. The presence of LZM in urine was associated with proximal tubular damage, which indicates that LZM-uria can be used as an index of renal tubular damage.