A 3 year old male Hungarian visla presented with a 4 week
history of polydipsia, polyuria, and progressive weight loss. Abdominal
radiography confirmed the abdominal distension is due to ascites; no other
radiographic abnormalities were detected.
A polydipsia profile reveals the following haematological
and biochemical abnormalities:
Haematology: Erythrocytosis (RBC 10.37 x1012/l; PCV
0.69 l/l; Hb 24.0 g/dl),and mild neutrophilia (11.7 x109/l).
Biochemistry: Total plasma proteins 38.5 g/l; hypoalbuminaemia
(9.9 g/l); hypocalcaemia (2.26 mmol/l); hypercholesterolaemia
(11.7 mmol/l).
Urinalysis (catheterized sample): Mild haematuria,
proteinuria (3+ on dipstick) and hyposthenuria (urine SG 1.005).
Urine microscopy was otherwise unremarkable.
Peritoneal fluid analysis: The gross specimen appeared
clear and colourless. Protein 1.8 g/l; SG 1.008; nucleated cells 0 x109/l;
RBC 0 x1012/l. Only a few mesothelial cells were seen on the cytospin preparation.
On the basis of these results what would be your tentative
diagnosis? What additional test(s) may be helpful? Please see page X for
an interpretive summary of the laboratory abnormalities described above.
Answer to the case challenge
The hypocellularity, low protein content and SG are typical of a true transudate,
hence the water-like appearance of this effusion. Hypoalbuminaemia can be
associated with chronic liver disease, glomerulonephropathy and protein-losing
enteropathy (PLE). With PLE globulins may also be significantly decreased
which is not the case here. 3+ protein on a urine dipstick is likely to
be significant given the low specific gravity and absence of an active urinary
sediment. The fact that cholesterol s also increased provides additional
support for a protein-losing nephropathy.
The extent of the urinary protein loss can be more precisely quantified
by measuring the urine protein:creatinine ratio (since it has been shown
that the UP:UC ratio on a single urine sample correlates well with measured
24 hour protein excretion). The UP:UC ratio in this case was 11.8 which
is high (normal usually less than 1.0). Values of this magnitude
are indicative of glomerular disease. Proteinuria, hypoalbuminaemia, hypercholesterolaemia
and ascites or subcutaneous oedema are classical features of the nephrotic
syndrome.
The erythrocytosis may simply be due to severe dehydration.
Equally, it is possible that this dog had absolute polycythaemia secondary
to renal disease. Secondary polycythaemia most frequently is associated
with renal disease eg renal lymphoma, pyelonephritis etc.
Two images of reactive mesothelial cells in peritoneal fluid.
SOME BACKGROUND INFORMATION
The main glomerular diseases in the dog are immune-complex glomerulonephritis
and amyloidosis. True autoimmune glomerulonephritis involving antibodies
against glomerular basement membrane antigens is thought not to occur in
the dog. Deposition of immune complexes in the capillary walls of the glomerulus
ultimately leads to malfunction of the entire nephron. Frequently, however,
during the earlier stages of the disease, nephron function remains adequate
hence urea and creatinine may be within reference limits (as was the
case here).
Glomerulonephritis can also be a manifestation of systemic
lupus erythematosus (SLE). Generally, however, dogs with SLE show
involvment of other body systems in addition to the kidneys eg joints (immune-mediated
polyarthritis), skin and blood (immune-mediated anaemia and/or thrombocytopenia).
Glomerulonephropathy may also be associated with leishmaniasis and, less
frequently, ehrlichiosis.
Amyloidosis may occur as a primary systemic disorder in
Shar peis. Secondary reactive amyloidosis, involving the deposition of amyloid
A (AA) protein, is associated with chronic inflammatory disease and
neoplasia. Differentiation of renal amyloidosis from immune-mediated glomerulonephritis
requires histological examination of a renal biopsy.
Dogs with glomerulonephritis usually do not develop oedema
or ascites until the albumin concentration is well below 15 g/l. Both albumin
and globulins may be lost in urine as the disease progresses (urine protein
electrophoresis may be helpful in this respect). Hypercoagulability
develops as a result of increased platelet adhesion and aggregation, and
the urinary loss of antithrombin. Pulmonary thromboembolism is therefore
an important potential complication of glomerulonephritis in dogs. Systemic
hypertension occurs in over 80% of dogs with glomerular disease and may
lead to retinal haemorrhage, detachment and papilloedema, and approximately
60% have hypercholesterolaemia which may also contribute to platelet hyperaggregability.
Treatment: The prognosis
for dogs with suspected immune-mediated glomerulonephritis is extremely
guarded; any response tends at best to be short lived. Azathioprine, chlorambucil,
cyclophosphamide and cyclosporine have been used either experimentally or
in clinical situations with variable and often disappointing results. The
administration of corticosteroids is controversial since it has been suggested
that they may actually increase the proteinuria and promote azotaemia. Aspirin
may be beneficial both for its anti-inflammatory and antithrombotic properties
if given at low doses (0.5 mg/kg once or twice daily). A low sodium
protein restricted diet is advised to minimize the risk of sodium retention
and systemic hypertension. The use of ACE inhibitors eg enalapril has yet
to be fully investigated.
Aknowledgments: Axiom Veterinary :Laboratories would
like to thank Helen Harper of the Shepton Vet Group, Shepton Mallet, Somerset
for allowing us to publish details of this interesting case. |