Transcript 28-Year-Old Man With Crohn Disease and Hematuria By Prof. Dr

28-Year-Old Man With Crohn
Disease and Hematuria
By Prof. Dr. Fawzy Megahed
4-3-2015
28-year-old man presented with a 3month history of mild abdominal
pain.
His medical history was notable
for Crohn disease diagnosed in
1994,
complicated by ileocolonic
resection (20 cm of ileum and 15
cm of the right colon removed)
in 2001.
He had been taking mesalamine
for 2 years, and although the
prednisone dose was increased
over the previous 3 months
because of recurrent abdominal
pain, it produced minimal relief.
Computed tomography (CT)
revealed fistulizing distal ileal
Crohn disease with abscess
formation.
The patient was hospitalized;
ertapenemand
vancomycin were initiated, and 2 trials of
CT guided
abscess drainage were attempted but
failed.
Twelve days after admission, the
patient
underwent laparotomy for abscess
drainage
without any surgical complications.
On postoperative
day 1, his vital signs deteriorated, with a
temperature of 39.3C, respiratory rate of
30
breaths/min, heart rate of 108 beats/min,
and
blood pressure of 130/80 mm Hg.
Pertinent
findings on examination included
mild respiratory
distress and rapid heart rate but
regular
rhythm and no murmurs.
His skin was warm
to touch, and no rashes or edema
were noted
on examination
A right lower quadrant drain
was in place with minimal bloodtinged drainage.
Evaluation included chest CT with
contrast medium, which ruled out
pulmonary embolism, and blood
cultures were obtained.
Intravenous ketorolac, 30 mg every 6
hours,
was initiated for fever and postoperative
pain management.
Blood culture results
remained
negative after 48 hours, and the
vancomycin
and ertapenem regimen was continued.
On postoperative day 3, laboratory testing
yielded
the following notable findings (reference
ranges
provided parenthetically):
• hemoglobin, 7.1 g/dL(13.5-17.5 g/dL);
• white blood cells (WBCs),14.7 109/L (3.510.5 109/L) with 13.8% neutrophils;
• sodium, 136 mmol/L (135-145mmol/L);
• potassium, 3.9 mmol/L (3.6-5.2 mmol/L);
• serum urea nitrogen, 12 mg/dL(8-24 mg/dL);
and creatinine, 1.6 mg/dL (0.8-1.3 mg/dL).
1. In patients with Crohn disease, which one of
the following is the most commonly
associated renal finding?
a. Renal cystic disease
b. Small vessel vasculitis
c. Medullary sponge kidney
d. Nephrolithiasis
e. Diabetic nephropathy
Patients with Crohn disease are at
considerable
risk for multiple lower genitourinary
tract and renal parenchymal and
interstitial
diseases.
Renal cystic disease encompasses a
wide spectrum of both genetic and
acquired
forms of renal cysts and has not been
associated
with inflammatory bowel disease
(IBD).
Small vessel vasculitis may be
associated with
antineutrophil cytoplasmic antibodies
and
manifest as microscopic polyangiitis,
granulomatous
polyangiitis, or Churg-Strauss
syndrome.
There have been case reports of
antineutrophil cytoplasmic antibodies
associated
vasculitis in patients with IBD, but
this association
is rare.
Medullary sponge kidney is a
congenital abnormality of the
collecting tubules
in the medullary region causing cystic
Dilatation.
Medullary sponge kidney has a
benign course but is associated with
hematuria,
nephrolithiasis, and recurrent urinary
tractinfections.
An association with IBD has not
been reported.
Nephrolithiasis is the most
commonly associated renal
disease in patients
with IBD.
Patients with IBD have a 12% to
28% incidence of nephrolithiasis
compared
with 5% in the general population.
Nephrolithiasis
tends to be more common in patients
with Crohn disease and a history of
ileocolonic
disease, as in this patient.
Diabetic nephropathy
has been reported in association with
prolonged
corticosteroid use in patients with IBD
who have development of diabetes, but it
does
not have a unique association with IBD
itself.
This patient had no history of chronic
kidney disease, proteinuria, hematuria,
or acute
kidney injury (AKI), and his baseline
creatinine concentration ranged
between 0.8 g/dL and 1.0
g/dL before the current admission.
He had
never passed a kidney stone.
Abdominal imaging
studies performed a few years before
admission
revealed no renal abnormalities.
During
the current hospitalization, AKI developed
and the creatinine level increased to
1.6 g/dL
within 48 hours and peaked at 2.1 g/dL.
Urinary
output declined to 500 mL in 24 hours
the day preceding the increase in
creatinine.
2. Which one of the following is the most
appropriate next step in the
management of this patient’s AKI?
a. Discontinue ertapenem and vancomycin
b. Discontinue ketorolac
c. Initiate N-acetylcysteine
d. Obtain vancomycin trough level
e. Repeat electrolyte panel
For several nephrotoxic drugs,
administration
can be suspended, the pattern of
administration
changed, or another less toxic or
nontoxic drug used instead.
However, this
strategy cannot be used for all potential
nephrotoxic medications.
Because the patient meets
the criteria for severe sepsis,
discontinuing antibiotics
may jeopardize his clinical status.
Evaluation for antibiotic-induced
nephrotoxicity
must be pursued before
discontinuation.
The nephrotoxicity of nonsteroidal antiinflammatory
drugs is mostly attributable to
inhibition of renal prostaglandin
synthesis.
They disrupt the compensatory
vasodilation
response of renal prostaglandins to
vasoconstrictor
hormones released in the context of
sepsis.
These aberrations
in renal hemodynamics
result in decreased cortical blood
flow, decreased glomerular filtration rate,
and
acute deterioration of renal function.
They
can also induce acute interstitial nephritis
(AIN).
Because the patient has had development
of AKI and there are other less
nephrotoxic
medications for pain control available,
the most reasonable next step in
management
is to discontinue ketorolac.
N-acetylcysteine
may reduce the nephrotoxicity of contrast
media through antioxidant and
vasodilatory
effects when given before administration
of contrast but not after the onset of
AKI.
Its
use is still controversial for prevention
of contrast-induced AKI.
Determining vancomycin
trough levels and repeating the
electrolyte
panel will be helpful to guide next steps,
but
the most important immediate next step
is
discontinuation of ketorolac.
Ketorlac was discontinued.
Further abdominal
imaging revealed a fluid collection extending
from the right subdiaphragmatic region to
the right lower quadrant that was concerning
for persistent abscess vs bowel leak as the
likely
cause for the persistent systemic inflammatory
response syndrome.
The vancomycin
level was monitored and noted to be elevated
at 30.1 mg/mL (<15 mg/mL).
Vancomycin
was withheld because of the supratherapeutic
levels, and the ertapenem dose was adjusted
for renal impairment.
Nephrology consultation
was requested.
3. Which one of the following is the best
test for evaluation of this patient’s AKI?
a. Urinalysis
b. Urinary eosinophil measurement
c. Complement level determination
d. Kidney ultrasonography
e. Measurement of the fractional excretion
of sodium (FENa)
Urinalysis is the most important step
in the
evaluation of AKI.
The urinalysis includes 2
components, an analysis for proteinuria,
leukocyte
esterase, glucosuria, bilirubin, and urinary
pH and microscopic examination of the
urinary sediment, which evaluates for
cells, crystals, and casts.
Quantification
of tubular cells and
casts correlates with biomarkers and
severity of AKI.
Assessment for red blood cells (RBCs),
WBCs, and various tubular cells and
casts will
guide the next steps in evaluation and
diagnostic work-up.
In clinical practice, urinary eosinophils
are often measured to help guide the clinician
in
determining whether AIN may be the cause of
AKI, and based on clinical impressions from
nephrologists,
sensitivities and specificities for urinary
eosinophils have ranged from 40% to 91%
and 52% to 95%, respectively.
Recent work
evaluating the diagnostic utility of urinary
eosinophil
measurement compared with kidney biopsy,
the criterion standard for diagnosis of
AIN,
found that the presence of urinary eosinophils
was not specific for AIN and may occur in many
renal disease processes; thus, it may not be
useful to differentiate AIN from acute tubular
necrosis.
Complement levels may be helpful when
an immune deposit glomerulonephritis is
suspected,
but its use should be based on clinical
suspicion in conjunction with the
presence of
RBCs on urinalysis.
Kidney ultrasonography is
useful to evaluate for the presence of
hydronephrosis
and kidney stones; however, it should
not
be the first step in AKI evaluation.
The FENa is
commonly used to differentiate
prerenal vs intrarenal
causes of AKI.
However,
the FENa has only
been found to reflect a sodium-avid
state or prerenal
state in oliguric cases of AKI.
Moreover, in
early phases of AKI, both intrarenal and
extrarenal
causes of AKI have been associated with
low
FENa values resembling those in the
prerenal state.
The cause of AKI should be based on
the global presentation including
history, clinical
examination, urinalysis, and response
to volume resuscitation.
Urinalysis revealed granular and
hyaline
casts, 4 to 10 WBCs per high-power
field,
and more than 180 RBCs per highpower field.
The protein to creatinine ratio and
albumin
levels were both normal.
Gram stain with urine
culture yielded negative results.
On the basis of the clinical scenario and
evidence of granular casts on urinalysis, the
cause of AKI in this patient was likely
multifactorial due to acute tubular necrosis
from several risk factors:
– severe sepsis,
– nonsteroidal anti-inflammatory
– drug use,
– recent contrast media exposure.
The degree of hematuria noted was
concerning
for a secondary process.
4. On the basis of this patient’s clinical
presentation, which one of the following is
the most likely explanation for the
hematuria?
a. Nephrolithiasis
b. Bladder malignant neoplasm
c. AIN
d. IgA nephropathy
e. Postinfectious glomerulonephritis
Nephrolithiasis can be asymptomatic
and
can cause marked hematuria in the
absence of proteinuria.
This patient has several risk factors
for nephrolithiasis including Crohn
disease,
history of ileocolonic involvement, and
ileal resection.
Considering the patient’s young age
and no smoking history, a bladder
malignant neoplasm is less likely to
explain this degree of
hematuria.
Although both RBCs and WBCs
can be present in AIN,WBCs are
usually present
in greater proportion than RBCs.
IgA nephropathy
usually manifests as microscopic
hematuria
in association with proteinuria and often
presents
at the onset of IBD or during a relapse.
Postinfectious glomerulonephritis is an
immunologic
response of the kidney that occurs after
a nonrenal infection, often with
streptococci,
and is associated with low complement
levels.
Proteinuria is an important
hallmark of this disease
process.
The presence of RBCs on urinalysis
prompted
measurements of total complement and
C3
and C4 levels.
The results were normal, which
in conjunction with the absence of any
proteinuria
makes the diagnosis of postinfectious
glomerulonephritis less likely.
A review of the
patient’s abdominal contrast CT on
admission
revealed multiple kidney stones in a
pattern
consistent with medullary
nephrocalcinosis,
likely explaining the hematuria.
The patient’s
renal function recovered to baseline
within 4
days after the creatinine concentration
peaked.
He underwent exploratory
laparotomy with
ileocolonic resection and ileostomy
for an anastomotic
leak.
The patient recovered and was
dismissed on the 23rd day of
hospitalization.
At follow-up 2 months after dismissal,
the
patient’s creatinine level remained
stable.
Urinalysis
continued to show hematuria and no
proteinuria
or microalbuminuria, consistent with
his underlying medullary
nephrocalcinosis.
He
underwent a 24-hour urinary metabolic
evaluation,
which yielded 2.9 L of urine, normal
urinary sodium and calcium levels, low urinary
pH (5.4), hypocitraturia, hypomagnesuria,
hyperuricosuria, and increased risk for
precipitation
of calcium oxalate and uric acid crystals.
5. On the basis of the 24-hour urinary
metabolic evaluation, which one of the
following is the most appropriate treatment?
a. Penicillamine
b. Sodium bicarbonate
c. Potassium citrate
d. Hydrochlorothiazide
e. Calcium carbonate
This patient has several urinary
metabolic
risk factors for nephrolithiasis.
In addition to careful adherence to
high-fluid, low-sodium,
low-purine dietary restriction,
medical therapy
is warranted to decrease the
likelihood of future
stone formation.
Penicillamine is a chelating
agent used for the treatment of
cystine nephrolithiasis.
It forms penicillamine-cysteine
disulfide
bonds that are easily excreted
compared
with cysteine-cysteine bonds.
There is no role
for the use of penicillamine in this
patient.
Sodium
bicarbonate therapy is helpful in patients
with evidence of non-anion gap metabolic
acidosis, which is often present in
patients
with chronic diarrhea.
This patient does not
have evidence of acidemia, and
therefore, treatment with sodium
bicarbonate is not warranted
at this juncture.
Potassium citrate is the mainstay
of therapy for patients with
hypocitraturia
and uric acid crystals.
Citrate inhibits stone formation
and alkalinizes the urine, which
increases
uric acid crystal solubility and
decreases uric acid stone formation.
Thiazide like
diuretics are useful in patients with
hypercalciuria
and calcium oxalate stones.
This patient has a normal
urinary calcium level.
Calcium
carbonate is often needed for
supplementation
in patients with low urinary calcium and
high urinary oxalate levels, as can be seen
in patients
with enteric hyperoxaluria.
However, this
patient has normal urinary calcium
and oxalate
levels, and therefore, calcium
supplementation
is not helpful.
The patient was encouraged to
continue
with high fluid intake and a lowsodium diet
and was educated about a low-fat,
low-purine
diet.
Potassium citrate tablets were
prescribed.
DISCUSSION
Crohn disease and ulcerative colitis are 2
distinct types of IBD and represent a
state of chronic T-celle mediated
inflammation that is heavily
influenced by genetic predisposition and
environmental and lifestyle factors.
Up to 23% of
patients with IBD will experience lower
genitourinary
tract and/or kidney involvement, namely
in the form of fistulizing disease,
interstitial renal disease, and
nephrolithiasis.
IgA nephropathy
has been reported as one of the most
common histopathologic findings on
kidney biopsies of patients with IBD and
is significantly more frequent in these
patients than in those without
IBD(24%vs8%;P<.01).
Several other intrarenal causes of kidney disease have been
reported in IBD
• AA (previously called secondary) amyloidosis,
which has been linked to chronic inflammation;
• interstitial nephritis, which has been associated
with salicylate therapy as an idiosyncratic drug
reaction (necessitating regular monitoring of
renal function);
• and in some reports as a possible direct
complication of IBD independent of treatment.
Nephrolithiasis in IBD may be
asymptomatic,
complicated by ureteral obstruction and
hydronephrosis, or associated with crystal
deposition
in renal parenchyma leading to interstitial
inflammation and fibrosis.
Patients with IBD
have a 12% to 28% incidence of
nephrolithiasis
compared with 5% in the general
population.
Patients with Crohn disease and
ileocolonic
involvement are more likely to have
development
of nephrolithiasis than patients with
ulcerative
colitis or colonic or ileal disease.
Two types
of nephrolithiasis predominate in
IBD:
• Calcium oxalate
• Uric acid stones.
There are dietary,
metabolic, and genetic risk factors that
predispose
to calcium oxalate stones including
hypercalciuria,
hyperoxaluria, hypocitraturia, and
strong family history.
Specific to gastrointestinal
disorders, patients with jejunoileal
bypass for
obesity and pancreatic insufficiency
are at highest
risk.
First, in patients with a diseased or
resected ileum, there is decreased
bile acid absorption,
which consequently leads to fat
malabsorption.
Calcium is bound by the intestinal
fat
through the process of
saponification, so there is
less calcium available to bind to
oxalate.
Second,
deconjugated bile salts have toxic
effects
on the colonic mucosa that may
directly factors.
Computed tomography
with a stone
protocol helps differentiate calcium- from
noncalcium-based stones and provides
insight
into whether stone burden necessitates
urological
intervention.
Review of previous imaging
studies will help determine if
stones are metabolically
active.
Urinary metabolic evaluation for
sodium,
calcium, oxalate, magnesium, and uric
acid will help individualize the
management
approach to minimize future stone
formation.
For patients with calcium oxalate stones,
the
focus of treatment is to increase the
luminal calcium
concentration with calciumcarbonate
supplementation
and dietary restriction of fat and
oxalate.
For those with uric acid stones, the
key treatment is alkalinization of the
urine
with potassium citrate, and if
hyperuricosuria
is present, allopurinol and a purinerestricted
diet are recommended.
Close follow-up is essential
to monitor nephrolithiasis risk
factors, adjust
treatment, and assess for changes in
stone type
over time.
Patients with IBD and risk factors
for nephrolithiasis benefit from
regular urinalysis
to assess for hematuria.
Patients with metabolically
active or symptomatic kidney stone
disease will benefit from tailored
treatment to
decrease further stone formation and
risk for
associated complications.
Thank
you