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Case
Report - A 19-year-old Female with Fever, Flank Pain,
and Bilateral Renal Cysts
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Matthew
Varughese, DO
A
19-year-old female with no significant past medical history
presented to the emergency room of an outside hospital with
a two day history of right sided flank pain and dysuria.
She also noted associated fevers, chills, nausea and vomiting
and denied hematuria or pyuria. Urinalysis showed 3+ hemoglobin
and frequent bacteria with few epithelial cells. She was
placed on oral amoxicillin-clavulanate and discharged. She
returned two days later with persistent nausea, vomiting,
worsening of her flank pain and a low grade fever. Laboratory
evaluation revealed a leukocyte count of 21,700/mm3 with 81% neutrophils and 12% band forms.
Urine culture from her initial visit grew greater than 100,000
colonies of Klebsiella pneumoniae sensitive to every antibiotic
tested except ampicillin. A computed tomography scan showed
bilaterally enlarged kidneys with numerous cysts. She was
admitted and treated with intravenous levofloxacin and ceftriaxone.
After four days, she was switched to oral trimethoprim/sulfamethoxesol
for two days and her leukocytosis and fever resolved. The
next day, her flank pain became more severe and she became
febrile to 104 degrees Fahrenheit. Intravenous antibiotics
were restarted and the patient was transferred to our facility
the next day.
On
initial exam, the patient was febrile and ill appearing
but hemodynamically stable. Physical examination revealed
right sided costovertebral angle tenderness of moderate
severity with referred pain to the right lower quadrant
of her abdomen. There was mild left sided costovertebral
angle tenderness as well. No masses were palpable and abdominal
examination was otherwise unremarkable. Leukocyte count
was 9,900/mm3 with no band forms, hemoglobin was 8.9 gm/dL
and hematocrit was 26.9%. Computed tomography of the abdomen
and pelvis showed bilaterally enlarged kidneys with scattered
cysts. Mild perinephric stranding, thickening of the right
conal fascia, and scattered areas of intracystic hyperdensities
consistent with prior hemorrhage were also noted. Renal
sonogram showed a right kidney measuring 15cm x 5cm x 5cm,
and a left kidney measuring 16cm x 7cm X 7cm. The left kidney
had 3 cysts in the upper pole, 5 in the mid pole, and 3
in the lower pole with the largest measuring 4cm. The right
kidney had 3 cysts in the upper pole with the largest measuring
1.3 cm. Renal sonogram screening of the mother was normal
but her father and brother both had bilateral renal cysts.
IMPRESSION
Her
initial failure to respond to antibiotic treatment, microscopic
hematuria, anemia, and bilateral renal cysts were all atypical
for uncomplicated pyelonephritis. The differential diagnosis
would include a pyocyst, infected cyst, ruptured cyst, cyst
hemorrhage, renal calculi with obstruction, anatomic anomalies,
perinephric abscess, and pelvic abscess. Although she presented
at an early age, the presence of bilateral renal cysts with
a positive family history of bilateral renal cysts in first
degree relatives strongly suggested the diagnosis of autosomal
dominant polycystic kidney disease with hemorrhage into
her renal cysts.
CLINICAL
COURSE
This
patient was admitted for a total of 16 days. Her antibiotics
were switched to oral form on day 9 as her nausea resolved.
There was a gradual improvement in her dysuria and defervescence
of her fever. She required large amounts of narcotics throughout
her course to control her pain. On hospital day 10, she
had increased somnolence and diminished breath sounds. A
chest x-ray revealed a large right pleural effusion with
right lower lobe atelectasis. A diagnostic and therapeutic
thoracentesis was performed showing an inflammatory exudate
without infective or malignant components. A repeat chest
x-ray two days later showed loculation of the right pleural
effusion which led to a successful, ultrasound-guided therapeutic
thoracentesis.
On
hospital day 14, the patient developed recurrent flank pain
and dysuria. Urine culture grew greater than 10,000 colonies
of methicillin resistent staphylococcus aureus. The patient
was given a one time dose of vancomycin and started on a
course of trimethoprim-sulfamethoxazole. By hospital day
16, her dyspnea, dysuria and leukocytosis had again resolved
and she was afebrile. Her pain had improved and she was
discharged home on a low dose fentanyl patch and to complete
a 21 day course of antibiotics.
DISCUSSION
Half
a million people in the United States are estimated to have
polycystic kidney disease. It has a prevalence of 1 in 400
to 1 in 1000 people in the white population2.
Although it is less common among American blacks the rate
of end stage renal disease due to autosomal dominant polycystic
kidney disease (ADPCKD) is similar in blacks and whites.
Thirty to fifty percent of individuals with ADPCKD will
have at least one kidney infection in their lifetime3.
Histologically,
ADPKD is characterized by an abnormal rate of tubule divisions.
As the ureteral bud advances, hypoplastic portions of tubules
are left behind. Cystic dilatation occurs in Bowman’s
capsule, the loop of Henle, and the proximal convoluted
tubule interspersed with normal renal tissue. Unlike the
contents of simple renal cysts which are biochemically similar
to plasma, the biochemical features of the fluid content
of cysts in ADPKD are closer to those of urine. This is
particularly true when samples are taken from distal nephrogenic
cysts. Stromal changes are nonspecific and similar to those
in other forms of renal failure. Dystrophic calcification
is also a common feature4.
In
order to properly manage patients with ADPCKD, it is important,
although often difficult, to distinguish between pyelonephritis
(renal parenchymal infection) from renal cyst infection
versus cyst hemorrhage. Often, cysts in these patients do
not communicate with a glomerulus. As a result, conventional
urine samples may never show signs of an infection and cultures
may also be unreliable. Therapeutically, this also affects
antibiotic therapy. Only antibiotics with certain properties
have been shown to reliably penetrate these cysts in adequate
concentrations to eradicate infection.
Clinical
judgement combined with patient presentation and imaging
will help narrow the diagnosis. In the absence of a positive
urine culture, patients with cystic hemorrhage often present
with acute flank pain of abrupt onset without significant
dysuria and frequency. Fever and leukocytosis if present
are generally transient. In acute pyelonephritis, urine
cultures are invariably positive and white blood cell casts
are also highly suggestive. Pyelonephritis will respond
more quickly to antibiotics than renal cyst infections.
Computed
tomography scans in acute cystic hemorrhage reveal high
attenuation, hyperdense masses on noncontrast scans. They
are generally subcapsular and gradually decrease in attenuation
as cystic bleeding decreases. Infected cysts have thick,
irregular walls that tend to calcify. Thickening of Gerota’s
fascia may be seen as well as gas within a cyst. Differentiation
between hemorrhage and infection is impossible with ultrasonography
alone as internal echoes and wall irregularites are seen
in both. Magnetic resonance imaging is useful in characterizing
complicated cysts and in patients who are allergic to iodinated
contrast or are at risk for contrast induced nephropathy5.
Treating
renal cystic infection is more difficult than simple pyelonephritis.
Up to six weeks of continued therapy is often necessary.
Cyst penetration and microbial coverage must be considered
when choosing antibiotic therapy. Gram-negative, enteric
aerobes ascending from the bladder are the most common organisms
encountered as with all urinary tract infections. In parenchymal
infection, susceptible organisms can be rapidly treated
with standard regimens of gentamicin and ampicillin. In
cyst infections, antibiotics must be chosen based on their
ability to enter the cyst via diffusion rather than filtration
due to the histology of the cysts and their frequent noncommunication
with a filtering glomerulus4.
The three most-studied antibiotics with appropriate antibiotic
coverage and diffusing capabilities are trimethoprim-sulfamethoxazole,
chloramphenicol, and ciprofloxacin. These agents are all
lipid-soluble which is essential for adequate diffusion
into the cyst. Clindamycin can be also used for anaerobic
coverage if needed. While all fluoroquinolones are lipid
soluble, the dipolar structure of ciprofloxacin has been
shown in numerous studies to attain high bactericidal concentrations
in cystic fluid within a short period of time5.
Surgical
care may be necessary for infected cysts that ultimately
fail antibiotic therapy or for cysts that are a persistent
disabling source of abdominal pain. Percutaneous ultrasound
guided pyocyst drainage is an option but it is technically
complex and also difficult to determine radiologically which
cysts are infected infected. Reducing a single, large cyst
with alcohol induced sclerosis is effective at reducing
pain and has been shown in one study to not significantly
affect renal function. At some institutions laparoscopic
denervation procedures have been perfected. For massive
cysts (over 40 cm) that are persistently infected and have
greater malignant potential, nephrectomy may be the only
treatment option1.
Urinary
tract symptoms in the setting of polycystic kidney disease
can be multi-factorial and difficulties can arise in bith
diagnosis and treatment. In our case, the patient may have
had a small component of pyelonephritis (as seen by perinephric
stranding on CT scan) but the majority of her symptoms were
likely due to renal cyst infection. Her initial urinalysis
before antibiotics were initiated showed some bacteria but
also epithelial cells. It had no white blood cell casts
or cells, and no nitrites or leukocyte esterase. She had
a prolonged course, requiring 21 days of hospital admission
in two institutions, and did not show a rapid response to
initial antibiotics. Although treatment was appropriately
directed towards the sensitivity of the organism, it may
have been less effective due to decreased cystic penetration.
Subsequent cultures did show clearance of the initial offender
(Klebsiella) but her persistent pain, dysuria, and fevers
suggested persistently infected cysts. In addition, her
consistent hemoglobinuria suggested that cystic hemorrhage
also contributed to her symptoms. This patient will need
close outpatient follow-up in order to treat flank pain
and dysuria aggressively early in the course with appropriate
antibiotics for cystic infections. Prophylactic antibiotics
may be warranted for recurrent infections.
REFERENCES
- Rose
BD, Bennett WH. Diagnosis, screening, mechanisms
of cyst growth, and urinary tract infections in polycystic
kidney disease. Up To Date. 2004
-
Brunwald E, Fauci AS, Kasper DL, Hauser SL, Longo
DL, Jameson JL. Polycystic kidney disease. In:
Brunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL,
Jameson JL. Harrison’s Principles of Internal
Medicine. 15th edition. McGraw Hill, 2001: 1598-1600
-
Gabow PA. Autosomal Dominant Polycystic
Kidney Disease. New England Journal of Medicine.1993,
329:323-342
-
Elzinga LW, Golper TA, Rashad AL, Carr ME, Bennett
WH. Ciprofloxacin activity in cyst fluid from
polycystic kidneys. Antimicrobial Agents and Chemotherapy.
1988. Vol.32 No.6: 844-847
-
Schuab SJ, Bander SJ, Klahr S. Renal Infection
in Autosomal Dominant Polycystic Kidney Disease. Am
J Med. 1987. Apr,82(4): 714-8
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