AJR 2001; 177:661-663
© American Roentgen Ray Society
CT Evaluation of Multisystem Involvement by Oxalosis
Lyn W. Kuo1,
Karen Horton and
Elliot K. Fishman
1
All authors: Department of Radiology, Johns Hopkins Hospital, 601 N. Caroline
St., Rm. 3254, Baltimore, MD 21287.
Received August 30, 2000;
accepted after revision February 22, 2001.
Address correspondence to E. K. Fishman.
Introduction
Hyperoxaluria is characterized by nephrolithiasis and nephrocalcinosis
caused by supersaturation of calcium oxalate in the urine. Primary
hyperoxaluria type 1 and 2 (PH1 and PH2) are rare autosomal recessive
disorders with defective glyoxylate metabolism in the liver resulting in
increased oxalate production
[1]. Secondary hyperoxaluria is
due to reduced excretion, excessive dietary intake, or increased gut
absorption of oxalate
[2,3,4].
Idiopathic hyperoxaluria has no known associated gene defect. When left
untreated, hyperoxaluria will ultimately lead to renal failure, which in turn
results in oxalosis, a condition in which calcium oxalate crystals are
deposited in extrarenal organs. Oxalate deposition most commonly affects the
bone, bone marrow, blood vessels, central nervous system, peripheral nerves,
retina, skin, and thyroid
[5].
We present an interesting case of a patient with primary hyperoxaluria and
oxalosis involving the kidneys, small intestine, skin, and heart. To our
knowledge, intestinal deposition of calcium oxalate has not been previously
reported.
Case Report
In April 1998, a 40-year-old woman presented at a hospital with a flulike
syndrome and acute renal failure that required hemodialysis. Her medical
history was notable for a prior episode of nephrolithiasis at the age of 14
years, which had required open stone extraction and bilateral knee operations
for cartilage injuries, and had resulted in right phrenic nerve palsy. There
was no family history of liver or kidney disease.
The patient was started on hemodialysis and discharged. Over the subsequent
6 months, she began experiencing a great deal of bone and joint pain as well
as refractory nausea and vomiting. She also developed severe extremity pain,
pruritus, and small palpable skin nodules in all extremities. These nodules
subsequently worsened, causing a mottled appearance and necrosis of the tips
of her great toes bilaterally and of areas on the dorsa of her feet. A skin
biopsy revealed calcium oxalate crystal deposits. A liver biopsy was then
performed, and the findings confirmed the diagnosis of primary hyperoxaluria.
At this time, the patient was referred to our hospital for further
treatment.
On presentation in April 1999, the patient still had mottled appearance of
the skin extending from the hands to the elbows and from the feet to the lower
thighs; tenderness, palpable deposits, and necrotic areas were also present in
these regions. All other findings at the physical examination were normal.
Laboratory studies were remarkable for a blood urea nitrogen level of 49 mg/dL
and creatinine level of 11.6 mg/dL. An unenhanced abdominal radiograph and CT
scan showed markedly dense kidneys compatible with extensive calcium oxalate
deposition and nephrocalcinosis (Figs.
1A and
1B). Increased attenuation of
the myocardium compatible with calcium oxalate deposition was noted on a later
unenhanced chest CT scan obtained when the patient was recovering from
pneumonia (Fig. 1C). An
electrophysiologic study failed to reveal any significant conduction
abnormality, and, therefore, no cardiac biopsy was performed. Performed as
part of an investigation of the patient's gastrointestinal tract complaints,
an upper endoscopy with a small-bowel biopsy in the third portion of the
duodenum revealed oxalate deposition (Fig.
1D).
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Fig. 1C. —40-year-old woman with primary hyperoxaluria and oxalosis.
Unenhanced chest CT scan shows increased attenuation of myocardium
(arrows), compatible with oxalate deposition. Note small pleural
effusion.
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Fig. 1D. —40-year-old woman with primary hyperoxaluria and oxalosis.
Microphotograph of biopsy specimen taken from third portion of duodenum at
endoscopy shows two polarizable calcium oxalate crystals (arrow) with
prismatic appearance along brush border in otherwise healthy small bowel. (H
and E, x200)
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The patient subsequently underwent combined liver and kidney
transplantation on August 8, 1999, that required retransplantation on August
11, 1999, because of primary non-functioning of the liver and possibly of the
transplanted kidney. The patient's native kidneys were left intact. Surgical
pathology of the explanted native liver showed polarizable crystals with
prismatic appearance consistent with oxalate crystals. The patient recovered
and was discharged in good condition.
Discussion
Hyperoxaluria is divided into three types: primary, secondary, and
idiopathic. There are two types of primary hyperoxaluria—PH1 and PH2. In
general, PH1 is more heterogeneous in presentation, more severe, and more
likely to produce crystal formation than PH2. It is caused by a defective
alanine—glyoxylate aminotransferase gene located on chromosome 2q37.3
that results in mistargeting of the enzyme. PH1 is much more prevalent in
Mediterranean countries, accounting for 13.5% of end-stage renal disease in
children compared with only 0.7% such disease in North America
[6]. PH2 is caused by a
defective glyoxylate reductase gene located on chromosome 9q11. Both enzymatic
defects result in increased oxidation of glyoxylate to oxalate.
Secondary hyperoxaluria can be due to impaired renal excretion; excessive
oxalate intake with ascorbic acid, methoxyflurane, ethylene glycol, and
xylitol ingestion; or increased absorption in patients with chronic
inflammatory bowel disease, small-bowel resection, intestinal bypass, and
external biliary drainage
[2,3,4].
Idiopathic hyperoxaluria has no known associated gene defect. Hypotheses of
possible causes include an inherent oxalate overproduction or possible
abnormal membrane transport of oxalate
[1,
4].
Most patients with hyperoxaluria present with renal calculi at an early age
[5], as did our patient. She
underwent open extraction of a renal stone at the age of 14 years, although
the diagnosis of oxalosis was not made at that time. As her renal failure
continued to progress, she began to experience other common disease
manifestations, such as progressive bone and joint pain because the bone is
the most common site of oxalate deposition
[3]. Her two previous knee
surgeries were, in retrospect, probably a direct result of the oxalosis. She
also had soft-tissue nodules and tissue necrosis, which were sequelae from
oxalate crystal deposition in the skin, another common site of involvement in
patients with oxalosis [5].
In addition to bone and skin involvement, our patient also had involvement
of the myocardium and small intestine. Cardiac involvement has been reported
and can lead to cardiomyopathy and arrhythmia, including a complete heart
block [5]. However, this
occurrence is rare. High density within the myocardium was revealed on an
unenhanced CT scan, although a cardiac biopsy was never performed to document
crystal deposition because the patient was asymptomatic. Also, she is unique
in that she also had crystal deposition in her small intestines, which may
account for her symptoms of nausea and vomiting. To our knowledge, intestinal
deposition has not been previously reported.
This patient's case also stresses the importance of early detection and
preventive treatment of the onset of renal compromise and systemic oxalosis
and, thus, of improved quality of life. First, increased water intake combined
with diuretics can dilute urine and facilitate oxalate excretion
[7]. Second, sodium citrate,
orthophosphate, phosphate loading, and daily magnesium
[4,
7] can inhibit calcium oxalate
crystallization by either alkalinizing the urine or by combining with oxalate
in the urine. Third, pyridoxine, a cofactor of alanine—glyoxylate
aminotransferase, can reduce oxalate production by enhancing the normal
conversion of glyoxylate to glycine
[4,
7]. Last, patients should be
advised to avoid oxalate-containing foods and beverages such as tea or cocoa
[7,
8].
For patients who already have renal failure and systemic oxalosis, as our
patient did, dialysis is not sufficient to prevent disease progression.
Therefore, surgical transplantation provides the only option. Between 10% and
50% of the kidneys implanted in isolated kidney transplantation have 5- to
10-year survival rates [8].
Isolated liver transplants have been performed, but universal consensus on the
optimal timing and success of the operation has not been reached. A combined
liver-and-kidney transplantation offers the most effective treatment because
the new liver will produce the necessary enzymes and the new kidney will
excrete oxalate normally. The transplanted liver has a 5-year survival rate in
80% of patients; the transplanted kidney has a 10-year survival rate in 70% of
patients [8]. Moreover, the
patient's plasma oxalate level returns to normal within a few days and urinary
oxalate excretion returns to normal over a period of 2-3 months. Deposits of
calcium oxalate in tissues can be remobilized and will resolve slowly over
time [8]. We have no follow-up
information because our patient returned to her home state after
discharge.
In summary, we presented a patient with primary hyperoxaluria who, because
of a delayed diagnosis, experienced extensive systemic oxalosis. Radiologists
should be aware of this condition because they may be the first to suggest the
diagnosis on basis of radiographic findings.
Acknowledgments
We thank John H. Yardley and May Arroyo for their input and help on the
pathologic slide.
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Introduction
Case Report
