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A 49-year-old female with a 5-year history of diabetes
mellitus type 2 presents for an initial visit. She has no
known complications of diabetes. She takes metformin,
glyburide, and aspirin. She does not use tobacco or alcohol.
On physical examination, you find a pleasant,
obese female in no distress. Her blood pressure is
136/86, pulse 86, respirations 14, and temperature
37°C. As you discuss monitoring of her diabetes, you
recommend screening for early kidney disease.
Which of the following approaches is the BEST
way to screen for diabetic kidney disease?
A) Obtain a 24-hour urine collection for albumin now
and again in 3 years.
B) Obtain a spot urine microalbumin every year.
C) Obtain a spot urine microalbumin/creatinine ratio
every year.
D) Obtain a urinalysis every year.
E) Obtain a serum creatinine every year.

The patient’s microalbumin/creatinine ratio is
42 mg/g. The next step to confirm
microalbuminuria is:

A) Repeat urine microalbumin/creatinine ratio.
B) Urine dipstick for protein.
C) 24 hour urine collection for total protein excretion.
D) Serum creatinine.

Which of the following can cause a false-negative
microalbumin/creatinine?
A) Vigorous exercise.
B) Fever.
C) Cachexia.
D) Poor glycemic control.
E) Large muscle mass.

What is the most appropriate next step in the
evaluation and management of this patient’s
microalbuminuria?
A) Start an ACEI.
B) Order renal ultrasound with Doppler of the renal
arteries.
C) Start insulin.
D) Refer to a nephrologist.

The patient has a full urinalysis to rule out renal inflammation
(eg, nephritis) and overt proteinuria (nephrotic
syndrome). The urinalysis is entirely negative.
What further investigations must your patient
undergo to eliminate other potential causes of
proteinuria?
A) Renal biopsy.
B) Renal ultrasound with Doppler of the renal arteries.
C) ANA, ESR, CRP.
D) All of the above.
E) None of the above.

You continue to follow this patient for several years.
Her disease progresses and insulin is eventually required.
She is admitted for chest pain, rules out for myocardial
infarction, and has a positive stress test. She
will need to have a cardiac catheterization.
In addition to holding her metformin, which of
the following interventions would be most likely
to reduce her risk of developing contrast-induced
nephropathy?
A) N-acetylcysteine and IV saline.
B) N-acetylcysteine and mannitol.
C) Sodium bicarbonate and IV saline.
D) Sodium bicarbonate and mannitol.
E) Mannitol and IV saline.

A) Obtain a 24-hour urine collection for albumin now
and again in 3 years.

C) Obtain a spot urine microalbumin/creatinine ratio
every year.
C) 24 hour urine collection for total protein excretion
C) Cachexia.
A) Start an ACEI.
D) All of the above.
A) N-acetylcysteine and IV saline.

C C A A C

C C A A A

Discussion
The correct answer is C. Microalbuminuria, which denotes
small amounts of albumin in the urine, is a
marker for possible future kidney disease in diabetics
(and others). The best test to evaluate for microalbuminuria
is the urine microalbumin/creatinine ratio. Its
advantages include ease of use, relatively low cost, and
good correlation with 24-hour urine collections. Since
albumin concentration is influenced by urine volume,
calculating a ratio between microalbumin and creatinine
eliminates the influence of volume and offers improved sensitivity and specificity compared with spot
urine microalbumin alone.
Some of you may have chosen answer B. Microalbumin
is the classic way to screen. As a practical matter,
many physicians use microalbumin alone as a
method of screening for urine protein, but this is not
the best test. A random spot urine microalbumin/
creatinine ratio is normally

CCCADA

Discussion
The correct answer is A. Verification by repeat urine
microalbumin/creatinine ratio is sufficient for a diagnosis
of microalbuminuria, so 24-hour urine collections (answer
C) need not be performed for confirmation. Since
protein excretion must exceed 300–500 mg per day for
a urine dipstick to detect proteinuria, urinalysis (answer
B) is not sensitive enough to detect microalbuminuria
and cannot be used for confirmation. Serum creatinine
elevation (answer D) may be a marker for diabetic kidney
disease, but it would develop late in the process.

Discussion
The correct answer is E. Patients with a large muscle
mass have a high rate of creatinine excretion, which may
result in a false-negative microalbumin/creatinine ratio
(as the urine creatinine goes up, the ratio goes down).
Patients with cachexia (answer C) have the opposite
problem, with low amounts of creatinine excretion,
resulting in false-positive microalbumin/creatinine
ratio. Fever (answer B), vigorous exercise (answer A),
heart failure, and poor glycemic control (answer D) can
cause transient microalbuminuria, potentially resulting
in false-positive microalbumin/creatinine ratios.

Discussion
The correct answer is A. For at least two reasons, the
next step should be initiation of an angiotensinconverting
enzyme inhibitor (ACEI) or an angiotensin
II receptor blocker (ARB). First, diabetes is known to
be a “coronary artery disease equivalent,” and your
patient has blood pressure in excess of the goal for
diabetics (

Discussion
The correct answer is E. No further evaluation is necessary
in this patient with microalbuminuria. The combination
of diabetic retinopathy (a marker for diabetic
renal disease), hypertension (BP >130/80 mm Hg in a
diabetic), and abnormal protein in the urine as measured
by the urine microalbumin/creatinine ratio is sufficient
to make the diagnosis of early diabetic nephropathy.
Renal biopsy (answer A) is quite invasive and unlikely to
change management. ANA, ESR, CRP (answer C), and
ultrasound (answer B) are unlikely to offer new information.
If things change (eg, nephritic urine, gross proteinuria,
etc), further evaluation may be indicated.

Discussion
The correct answer is C. Sodium bicarbonate (isotonic
sodium bicarbonate solution at 3 mL/kg for 1 hour
before the procedure and continue at 1 mL/kg for
6 hours after the procedure) has good evidence for
benefit with little risk. For patients at risk of contrastinduced
nephropathy, including those with creatinine
≥1.5 mg/dL, contrast studies should be avoided if possible,
using ultrasound non-contrast MRI or other
modalities. If a contrast study must be done, there are
several interventions shown to reduce the risk of
contrast-induced nephropathy. First, aggravating medications
like NSAIDs should be held. Plenty of hydration,
usually with IV saline, should be given if there are
no contraindications (eg, heart failure). Nonionic lower
osmolality (or even iso-osmolar) contrast agents should
be used. N-acetylcysteine has conflicting evidence, but
it is still often used along with sodium bicarbonate and
IV hydration. The diuretics mannitol and furosemide
may be associated with an increased risk of nephropathy,
and mannitol in particular has an undesirable side
effect profile.