ISRAEL JOURNAL OF
VETERINARY MEDICINE
CYSTINE UROLITHIASIS IN A CAT - FIRST REPORT IN ISRAEL
1
Amiel S., 1Zaretsky A., 1Zamiri E., 1Neoman G and 2Waner T.
1. Zaretsky and Amiel Veterinary Clinic Ltd., 20 Akko Road, Kiriat Bialik 27093, Israel.
2. Rehovot Veterinary Clinic, 9 Meginay Hagalil Street, Rehovot 76200, Israel.
Summary
This case report describes a rare condition of cystine urolithiasis in a spayed
female Siamese cat. The uroliths were analyzed and found to be composed of
100% cystine. The condition was accompanied by apparent kidney failure. The
report describes the clinical presentation, diagnosis and treatment. This is the first
report of cystine urolithiasis in a cat in Israel and the Middle East.
Introduction
Cystine urolithiasis is the formation of cystine crystals and uroliths in the urinary
system. The condition has been extensively studied in humans and dogs however
there is dearth of information about its pathophysiology in the cat (1) . The condition
is very rare in the cat and occurs predominately in domestic shorthaired breeds and
Siamese cats (2) . An effective treatment protocol for the dissolution of the stones or
their delayed formation has not been developed to date. This report describes the
clinical presentation, diagnosis and treatment of a cat with cystine urolithiasis. To the
best of the authors’ knowledge this is the first report of cystine urolithiasis in a cat in
Israel and the Middle East.
Case report
A five and half year old Siamese neutered female cat was presented with a complaint
that she was spending prolonged periods of time at her litter box and that the owners
suspected that she may be suffering from either constipation or dysuria. In addition
the owner noticed that she had lost significant body weight over the last few weeks.
The cat was an indoor cat and had not been vaccinated over the last four years. She
had been fed a feline commercial dry food; lately however, the owners had been
feeding a canned commercial feline diet.
A complete physical examination did not reveal any abnormalities other than a mild
painful reaction when palpated in the region of the posterior abdomen. Due to the lack
of any significant findings the cat was treated with a laxative and the owners were
requested to return with a urine sample for urinalysis.
A few days later, the owners reported that the cat's condition had deteriorated and that
she was anorexic, inactive, vomiting, and anuric for two days. On physical
examination the following changes were detected: hypothermia (36oC), dehydration
(estimated at 8%) and painful posterior abdomen. Palpation of the bladder revealed
the presence of urinary stones. Radiology of the abdomen revealed a large number of
round stones within the bladder.
At this stage hematology and clinical chemistry was carried out (Tables 1 and 2). The
complete blood count was unremarkable. The most striking abnormal clinical
chemistry results were a marked increase in serum urea and creatinine concentrations.
Plasma sodium levels were decreased whereas potassium was increased. Total serum
protein, albumin and globulin were all significantly decreased. Other changes
included a mild increase in enzyme activity of asparate aminotransferase (AST) and
amylase.
Urinalysis results revealed hematuria (>250 erythrocytes/µL), proteinuria (estimated
15 g/dL), specific gravity (SG) of 1.020 and a pH of 6.5. The urine was negative for
glucose and bilirubin. Microscopic examination of the sediment showed only a few
crystals that appeared to resemble triple-phosphate. A large number of leukocytes and
erythrocytes and a few granular casts were identified.
Treatment
At first treatment was aimed at correcting the fluid and electrolyte imbalances and
treating the uremic gastritis, and secondly to attend to the primary condition of
urolithiasis. In view of the clinical picture and the clinical chemistry results the
treatment was initiated and consisted of:
1. Intravenous fluids consisting of Ringers lactate and 10% dextrose solution (Teva
Pharmaceuticals, Ashdod, Israel) to correct the fluid balance and attend to the
apparent renal failure.
2. Phenoxybenzamine (Dibenyline, Goldshield Pharmaceuticals, U. K) was dosed at a
prescribed amount of 0.25mg/kg per os q12h to reduce the internal urethral sphincter
tone and allow for the passing of small uroliths.
3. Cimetidine HCl (Cemidin, Dexxon, Israel) and metoclopramide HCl (Praminin,
Rafa, Israel) was dosed orally at a dosage of 5mg/kg and 0.2mg/kg q8h, respectively
to treat uremic gastritis.
4. Antibiotics were administered: cefazolin (Cefamezin, Teva, Israel) and
enrofloxacin (Baytril, Bayer, Germany) at a dose of 30mg/kg q8 IM and 5mg/kg per
day PO, respectively.
5. A calculolytic diet (S/D feline formula, Hill’s Prescription Diet) was fed bearing in
mind that the most prevalent uroliths are formed from struvite . The cat was
hospitalized for two days.
The owners were asked to return with the cat to follow-up the serum creatinine and
urea concentrations. Two days after initiation of treatment the serum urea level had
returned to normal (28.5 mg/dL). At this stage the general demeanor of the cat had
improved although she did not appear to have returned to her normal self and
appeared to be experiencing abdominal pain.
Four days later the general condition of the cat had deteriorated and it was then
decided to remove the urinary calculi by surgery due to the painful situation.
Cystotomy was carried out and after removal of an abundant number of calculi, the
bladder was repeatedly lavaged to remove any residual sediment. Samples of the
stones were sent for analysis to the Urolith Center at the University of Minnesota,
United States of America (3). The cat recovered well from the surgical procedure and
was released on supportive treatment and antibiotics. The cat was now fed a dry
calculolytic diet (Renal Programme Diet, Royal Canin).
The results of the urolith analysis revealed that the stones were composed of 100%
cystine (4) . In the light of these results the diet was changed to Hill’s K/D feline
formula (Hill's Prescription Diet). The owners were advised to add salt to the diet to
encourage the cat to drink more water and promote an increased urinary volume. In
addition a low dose of diuretics was initiated. About two months after the surgical
procedure the condition of the cat began to deteriorate. Examination revealed the
presence of multiple uroliths that were newly formed. In view of the prognosis and
the need for further surgical procedures the owners elected to euthanize the cat.
A full post mortem was carried out. Multiple uroliths were identified in the urinary
bladder. Histological examination of the kidney revealed mild mineralization of the
renal medulla without any other pathological findings in the kidneys or any other
organ.
Discussion
Cystine urolithiasis is the formation of cystine crystals and uroliths in the urinary
system. The condition has been extensively studied in humans and dogs and there is
dearth of information about the pathophysiology in the cat (5,6) . Cystine is a sulfuramino acid that is normally present in low concentrations in plasma. Normally it is
freely filtered by the glomeruli and is then actively reabsorbed by the proximal
tubules. Cystine urocystoliths arise due to an inborn error in metabolism characterized
by an abnormal transport of cystine by the renal tubules.
The presence of cystine uroliths in cats is very rare, and cystine uroliths accounts for
about 0.2% of all mineral uroliths types found in cats . In this case the signalment for
the presence of cystine uroliths was in accordance with that described in the literature
. Cystine uroliths occur in both male and females cats at similar frequencies primarily
at about 4 years of age. Domestic Shorthaired (65%) and Siamese (20%) cats are
more commonly affected. The initial clinical signs are usually characteristic of feline
lower urinary tract disease as was seen in this case and may include hematuria,
dysuria, pollakiuria and urethral obstruction. Cystine crystaluria is a characteristic
finding in urine samples from cats with cystine urocrytoliths.
The cat described in this case also developed transient renal failure. The reason for
this occurrence in unclear and has not been described previously in cats with cystine
uroliths. A human study showed that impairment of renal function is common in
patients with stone-forming cystinuria (7) . Furthermore, another human study
attempted to determine the potential impact of cystinuria and cystine stone formation
on the level of renal function compared to calcium oxalate stone formers . They found
that a significantly greater percentage of cystinuric patients had an abnormally
increased serum creatinine compared to calcium oxalate stone formers (8). The postmortem findings did not support any chronic renal changes and so it appears that that
the azotemia and increased creatinine levels were due to acute changes in the kidney
which resulted in acute transient renal failure. The possibility of post-renal changes
due to obstruction of the ureters by uroliths cannot be discounted, although there were
no pathological findings to support this option.
The possibility that this cat may have also had hypoadrenocorticism cannot be
discounted entirely, although the syndrome is very rare in cats. The dehydration and
vomiting, as well as the low serum sodium and high serum potassium along with low
blood glucose may have been indicative of Addison’s disease. This was not
considered at the time of the diagnosis but in retrospect should have been an element
in a differential diagnostic list.
The treatment of cystine uroliths in cats to promote their dissolution is problematic.
N-2-mercatopropionyl-glycine (2-MPG) has been used successfully in dogs and some
cats to decrease cystine uroliths (9,10,2) . The drug undergoes thiol-disulfide
exchange with cystine to form a more soluble product that is readily excreted.
However 2-MPG is considered anecdotally to be toxic for cats and its use is
questionable. Complicating the treatment further is the rapid rate of recurrence of
cystine uroliths, which range from 2 weeks to about 3 months. In the Siamese cat
described here the rate of recurrence was about 2 months after surgical removal of the
cystine uroliths. Urohydropropulsion of cystine uroliths has been attempted with
moderate success (2) . This technique however requires early detection of the uroliths
by radiology while they are still small, and constant and recurrent therapy throughout
life.
Cystine is more soluble in an alkaline environment and the use of a high moisture (to
increase urine volume) and alkalinizing diet is advisable. In this case renal failure diet
was fed, which would also give the added advantage of a low protein diet. Despite the
diet the cystine uroliths formed rapidly over a period of two months. It therefore
appears that this form of therapy was unsuccessful in this case.
In conclusion, this case report describes a rare condition of pure cystine uroliths in a
female Siamese cat. The cat also displayed transient acute renal failure, an associate
condition that has not been described previously in cats with cystine urolithiasis. This
is the first report of cystine urolithiasis in a cat in Israel and the Middle East.
Acknowledgements
The authors would like to acknowledge the assistance and support of Prof. Charles
Osborne, and Prof. Shimon Harrus for his encouragement.•
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