RESIDENTS’ CLINIC
28-Year-Old Man With Crohn Disease and
Hematuria
Diana L. Franco, MD, and Mira T. Keddis, MD
A
28-year-old man presented with a 3-
month history of mid abdominal
pain. His medical history was notable
for Crohn disease diagnosed in 1994, compli-
cated 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 mini-
mal relief. Computed tomography (CT) revealed
fistulizing distal ileal Crohn disease with abscess
formation.
The patient was hospitalized; ertapenem and
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 postop-
erative day 1, his vital signs deteriorated, with a
temperature of 39.3 C, 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 respira-
tory 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 blood-tinged
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 (3.5-10.5  109/L) with 13.8%
neutrophils; sodium, 136 mmol/L (135-145
mmol/L); potassium, 3.9 mmol/L (3.6-5.2
mmol/L); serum urea nitrogen, 12 mg/dL
Mayo Clin Proc. n December 2014;89(12):e123-e127 n http://dx.doi.org/10.1016/j.mayocp.2014.04.036
www.mayoclinicproceedings.org n ª 2014 Mayo Foundation for Medical Education and Research
(8-24 mg/dL); and creatinine, 1.6 mg/dL (0.8- See end of article
1.3 mg/dL). for correct answers
to questions.
1. In patients with Crohn disease, which Resident in Internal Medicine,
one of the following is the most Mayo School of Graduate
commonly associated renal finding? Medical Education, Mayo
Clinic, Scottsdale, AZ (D.L.F.);
a. Renal cystic disease Advisor to resident and
b. Small vessel vasculitis Consultant in Nephrology,
c. Medullary sponge kidney Mayo Clinic, Scottsdale, AZ
(M.T.K.).
d. Nephrolithiasis
e. Diabetic nephropathy
Patients with Crohn disease are at consid-
erable 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 associ-
ated with inflammatory bowel disease (IBD).
Small vessel vasculitis may be associated with
antineutrophil cytoplasmic antibodies and
manifest as microscopic polyangiitis, granulo-
matous polyangiitis, or Churg-Strauss syn-
drome. There have been case reports of
antineutrophil cytoplasmic antibodyeassoci-
ated vasculitis in patients with IBD, but this as-
sociation is rare. Medullary sponge kidney is a
congenital abnormality of the collecting tu-
bules in the medullary region causing cystic
dilatation. Medullary sponge kidney has a
benign course but is associated with hematu-
ria, nephrolithiasis, and recurrent urinary tract
infections. 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.1 Nephroli-
thiasis tends to be more common in patients
with Crohn disease and a history of ileocolonic
disease, as in this patient. Diabetic nephropa-
thy has been reported in association with pro-
longed corticosteroid use in patients with IBD
who have development of diabetes, but it does
not have a unique association with IBD itself.
e123

This patient had no history of chronic kid-
ney 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 imag-
ing studies performed a few years before admis-
sion 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. Uri-
nary 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, administra-
tion can be suspended, the pattern of adminis-
tration changed, or another less toxic or
nontoxic drug used instead. However, this
strategy cannot be used for all potential neph-
rotoxic medications. Because the patient meets
the criteria for severe sepsis, discontinuing an-
tibiotics may jeopardize his clinical status.
Evaluation for antibiotic-induced nephrotoxi-
city must be pursued before discontinuation.
The nephrotoxicity of nonsteroidal anti-
inflammatory drugs is mostly attributable to
inhibition of renal prostaglandin synthesis.2
They disrupt the compensatory vasodilation
response of renal prostaglandins to vasocon-
strictor hormones released in the context of
sepsis.3 These aberrations in renal hemody-
namics 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 develop-
ment of AKI and there are other less nephro-
toxic 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
n n
e124 Mayo Clin Proc. December 2014;89(12):e123-e127
MAYO CLINIC PROCEEDINGS
contrast but not after the onset of AKI.4 Its
use is still controversial for prevention of
contrast-induced AKI. Determining vancomy-
cin 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 abdom-
inal imaging revealed a fluid collection extend-
ing 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 trough
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, leuko-
cyte 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.5 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 ne-
phrologists, sensitivities and specificities for uri-
nary eosinophils have ranged from 40% to 91%
and 52% to 95%, respectively.6 Recent work
evaluating the diagnostic utility of urinary eosin-
ophil measurement compared with kidney bi-
opsy, the criterion standard for diagnosis of
AIN, found that the presence of urinary eosino-
phils was not specific for AIN and may occur in
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RESIDENTS’ CLINIC
many renal disease processes; thus, it may not be
useful to differentiate AIN from acute tubular ne-
crosis.6 Complement levels may be helpful when
an immune deposit glomerulonephritis is sus-
pected, 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 hydroneph-
rosis and kidney stones; however, it should not
be the first step in AKI evaluation. The FENa is
commonly used to differentiate prerenal vs intra-
renal causes of AKI. However, the FENa has only
been found to reflect a sodium-avid state or pre-
renal state in oliguric cases of AKI. Moreover, in
early phases of AKI, both intrarenal and extrare-
nal causes of AKI have been associated with low
FENa values resembling those in the prerenal
state.7 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 high-power 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 pa-
tient was likely multifactorial due to acute
tubular necrosis from several risk factors: se-
vere sepsis, nonsteroidal anti-inflammatory
drug use, and 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.8 Considering the patient’s young age
and no smoking history, a bladder malignant
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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 nephropa-
thy usually manifests as microscopic hematuria
in association with proteinuria and often pre-
sents at the onset of IBD or during a relapse.
Postinfectious glomerulonephritis is an immu-
nologic response of the kidney that occurs after
a nonrenal infection, often with streptococci,
and is associated with low complement levels.9
Proteinuria is an important hallmark of this dis-
ease process.
The presence of RBCs on urinalysis promp-
ted measurements of total complement and C3
and C4 levels. The results were normal, which
in conjunction with the absence of any protein-
uria 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 anas-
tomotic 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. Urinal-
ysis continued to show hematuria and no pro-
teinuria or microalbuminuria, consistent with
his underlying medullary nephrocalcinosis. He
underwent a 24-hour urinary metabolic evalua-
tion, 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 precipi-
tation 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
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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 nephro-
lithiasis. It forms penicillamine-cysteine disul-
fide bonds that are easily excreted compared
with cysteine-cysteine bonds. There is no role
for the use of penicillamine in this patient. So-
dium bicarbonate therapy is helpful in patients
with evidence of noneanion gap metabolic
acidosis, which is often present in patients
with chronic diarrhea. This patient does not
have evidence of acidemia, and therefore, treat-
ment with sodium bicarbonate is not warranted
at this juncture. Potassium citrate is the main-
stay of therapy for patients with hypocitraturia
and uric acid crystals. Citrate inhibits stone for-
mation and alkalinizes the urine, which in-
creases uric acid crystal solubility and
decreases uric acid stone formation. Thiazide-
like diuretics are useful in patients with hyper-
calciuria and calcium oxalate stones. This
patient has a normal urinary calcium level. Cal-
cium carbonate is often needed for supplemen-
tation in patients with low urinary calcium and
high urinary oxalate levels, as can be seen in pa-
tients 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 low-sodium 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-cellemediated inflammation that is heavily
influenced by genetic predisposition and envi-
ronmental and lifestyle factors. Up to 23% of
patients with IBD will experience lower genito-
urinary tract and/or kidney involvement, namely
in the form of fistulizing disease, interstitial renal
disease, and nephrolithiasis.8 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% vs 8%; P<.01).10 Several other intra-
renal causes of kidney disease have been reported
in IBDdAA (previously called secondary)
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e126 Mayo Clin Proc. December 2014;89(12):e123-e127
MAYO CLINIC PROCEEDINGS
amyloidosis, which has been linked to chronic
inflammation; interstitial nephritis, which has
been associated with salicylate therapy as an
idiosyncratic drug reaction (necessitating reg-
ular monitoring of renal function); and in
some reports as a possible direct complication
of IBD independent of treatment.11
Nephrolithiasis in IBD may be asymptom-
atic, complicated by ureteral obstruction and
hydronephrosis, or associated with crystal depo-
sition 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.1
Patients with Crohn disease and ileocolonic
involvement are more likely to have develop-
ment of nephrolithiasis than patients with ulcer-
ative colitis or colonic or ileal disease. Two types
of nephrolithiasis predominate in IBD: calcium
oxalate and uric acid stones. There are dietary,
metabolic, and genetic risk factors that predis-
pose to calcium oxalate stones including hyper-
calciuria, hyperoxaluria, hypocitraturia, and
strong family history. Specific to gastrointestinal
disorders, patients with jejunoileal bypass for
obesity and pancreatic insufficiency are at high-
est risk. First, in patients with a diseased or
resected ileum, there is decreased bile acid ab-
sorption, which consequently leads to fat malab-
sorption. Calcium is bound by the intestinal fat
through the process of saponification, so there is
less calcium available to bind to oxalate. Thus,
there is increased oxalate absorption via the co-
lon, also known as enteric hyperoxaluria. Sec-
ond, deconjugated bile salts have toxic effects
on the colonic mucosa that may directly
enhance oxalate absorption. Third, several bio-
logical inhibitors of kidney stones such as citrate
and magnesium have been found to be low in
the urine of patients with IBD. Uric acid stones
occur predominantly in the context of chronic
diarrhea, which may lead to noneanion gap
metabolic acidosis that then drives increased uri-
nary acid excretion. Low urinary pH is a major
risk for uric acid crystallization and stone forma-
tion. Moreover, most patients with chronic diar-
rhea are at risk for hypovolemia, and low urinary
volume is another important risk factor for stone
formation.
In evaluating patients with nephrolithiasis,
imaging studies and a complete urinary meta-
bolic evaluation are needed to determine stone
type, size, location, metabolic activity, and risk
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RESIDENTS’ CLINIC
factors. Computed tomography with a stone
protocol helps differentiate calcium- from
noncalcium-based stones and provides insight
into whether stone burden necessitates urologi-
cal intervention. Review of previous imaging
studies will help determine if stones are metabol-
ically active. Urinary metabolic evaluation for so-
dium, 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 cal-
cium concentration with calcium carbonate sup-
plementation and dietary restriction of fat and
oxalate.12 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 purine-restricted
diet are recommended. Close follow-up is essen-
tial 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 urinaly-
sis to assess for hematuria. Patients with meta-
bolically active or symptomatic kidney stone
disease will benefit from tailored treatment to
decrease further stone formation and risk for
associated complications.
Correspondence: Address to Mira T. Keddis, MD, Division
of Nephrology, Mayo Clinic, 5777 East Mayo Boulevard,
Phoenix, AZ 85054 (keddis.mira@mayo.edu).
Mayo Clin Proc. n December 2014;89(12):e123-e127 n http://dx.doi.org/10.1016/j.mayocp.2014.04.036
www.mayoclinicproceedings.org
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CORRECT ANSWERS: 1. d. 2. b. 3. a. 4. a. 5. c
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