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Nephrology – Proteinuria

SOAP Note
with Manish Suneja, MD

INTRODUCTION

Normally, adults excrete less than 150mg of protein in the urine every day. Proteinuria refers to
the urinary excretion of protein in amounts exceeding 150mg/day. When the excretion is >3.5g/
day, this is classified as nephrotic range proteinuria and usually indicates significant primary or
secondary renal pathology.

Managing proteinuria can seem like a daunting task. However, a careful history and physical
examination and judicious use of investigations will help you determine the underlying
pathology and develop an appropriate management strategy.

SUBJECTIVE

If the proteinuria is severe, patients will often complain of foamy urine, feeling tired or dizzy, or
may say they have noticed swelling of their hands and feet. More often than not, the proteinuria
is picked up on routine investigations and patients will be asymptomatic. When you see such a
patient, there are several key questions to ask in history.

• Has the patient been ill recently or participated in intense exercise? Do they ever get
dizzy after standing for too long?
• These questions can help screen for exercise or fever induced transient proteinuria
and for orthostatic proteinuria. Keep in mind though that some causes of fever, such
as streptococcal infection or viral hepatitis, can lead to significant glomerular disease.
As such, a thorough infectious disease and travel history should be undertaken in any
patient presenting with fever and proteinuria.
• Do they have a history of diabetes or hypertension?
• If the patient admits to either of these, further questioning should be aimed at
determining how well their condition is managed and if they are adhering to their
medication regimen. Poorly controlled diabetes and hypertension are among the
leading causes of chronic kidney disease and proteinuria is often the first and only
sign of nephropathy in these patients.
• Have they ever been diagnosed with kidney disease, autoimmune diseases, or
malignancy?
• Proteinuria in a patient with prior history of renal disease, such as polycystic kidney
disease or membranous nephropathy, may indicate a worsening of these conditions.
Patients with known history of autoimmune conditions, such as lupus, or a
malignancy, and who are now presenting with proteinuria should alert you to renal
involvement. 


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• Has the patient noticed any blood in the urine?
• Think of focal or diffuse nephritic causes of glomerular disease in patients with
hematuria and proteinuria. These include membranoproliferative glomerulonephritis,
focal proliferative glomerulonephritis, and diffuse proliferative glomerulonephritis.
Painless hematuria can be a sign of bladder or renal malignancy and should be further
evaluated.
• Ask about medications.
• Certain medications (i.e. NSAIDs, gold) are reversible causes of renal injury and
proteinuria.

OBJECTIVE

Physical Exam

There are very few signs specific to proteinuria itself. As mentioned, in severe cases, patients
may present with edema of the hands and feet or with generalized edema (anasarca). Nephrotic
range proteinuria may result in volume overload and the patients can present with pleural
effusions, ascites, and peripheral edema with resultant shortness of breath and abdominal
distension. Evaluation of the vital signs may reveal fever, hypotension, and tachycardia.
Orthostatic vitals should also be measured.

More generally, physical examination of a patient with proteinuria should be aimed at


determining an underlying cause. Check for signs of diabetes, hypertension, and other systemic
illnesses, such as vasculitis or malignancy. In severe, nephrotic range proteinuria, examination
should also focus on assessing for complications, such as hypovolemia, protein malnutrition,
renal vein thrombosis, deep vein thrombosis, and infection.

Lab Work

Laboratory investigations should be aimed at confirming and quantifying proteinuria and trying
to determine the cause. A standard urine dipstick will help confirm proteinuria. Keep in mind,
though, that standard dipstick analysis is sensitive to albumin, but not to other proteins that
may be excreted. In contrast, a sulfosalicylic acid (SSA) test detects all urinary proteins and
can be used in patients with signs and symptoms of multiple myeloma or those with signs of
acute kidney injury but negative dipstick.

While a 24-hour urine collection is the gold standard for quantifying proteinuria, it can
sometimes be improperly collected (i.e. under or over-collection) and can be cumbersome to
some patients. Acceptable alternative methods for quantifying proteinuria include measuring
the urine albumin-to-creatinine ratio (UACR) or urine protein-to-creatinine ratio (UPCR) in a
random urine sample. Quantifying proteinuria is important clinically as it will help you narrow
down your differentials and help in monitoring response to treatment.

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The following table lists the values to look for on these tests and what they mean:

24-hour Collection Random Urine Sample Meaning


>150 mg/day total protein >150 mg/g total protein Proteinuria
30-300 mg/day albumin 30-300 mg/g albumin Moderately increased
albuminuria (formerly
called microalbuminuria)

>300 mg/day albumin >300 mg/g albumin Severely increased


albuminuria (formerly
called macroalbuminuria)
>3500 mg (3.5g)/day of >3500 mg/g (or >3.5) total Nephrotic Range
total protein protein

Additional investigations include:

• Complete blood count (i.e. checking for anemia of chronic disease, leukocytosis
indicating infection).
• Serum creatinine levels to calculate eGFR, blood glucose or HbAIC for assessment of
diabetes mellitus.
• Autoantibody levels (if indicated).
• Renal ultrasound can help assess for structural causes.
• Urine and serum electrophoresis studies can check for presence of monoclonal light
chains (indicative of multiple myeloma).
• In patients with a combination of proteinuria and hematuria, which is consistent with
glomerulonephritis/nephritic syndrome, further workup should include checking
complements including CH50, C3, and C4 (to evaluate for immune complex disorders),
antineutrophil cytoplasmic antibody (to evaluate for possible pauci-immune vasculitis),
and anti-GBM antibody (to evaluate possible anti-GBM disease or Goodpasture
syndrome).
• If the complement levels are depressed, further work up with autoantibodies and
serologies should be performed to evaluate for SLE, postinfectious glomerulonephritis,
cryoglobulinemia/hepatitis C, or membranoproliferative glomerulonephritis.

The presence of nephrotic-range proteinuria with edema, hypoalbuminemia, and hyperlipidemia


is consistent with nephrotic syndrome. Further work up for these patients include blood glucose
or HbA1C for assessment of diabetes mellitus, urine and serum electrophoresis studies to look
for the presence of monoclonal light chains (indicative of multiple myeloma or amyloidosis),
HIV testing (especially if clinical suspicion of HIV), autoantibodies for SLE (ANA and dsDNA)
and serologies for possible Hepatitis B and C.

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In patients who have proteinuria and associated decreased GFR or active urine sediments (i.e.
hematuria with dysmorphic red blood cells or red blood cell cast) or with nephrotic range
proteinuria, a renal biopsy may be warranted. A referral to nephrology should also be made at
this point.

ASSESSMENT AND PLAN

Management of proteinuria ultimately depends on the underlying etiology.

• In asymptomatic patients with proteinuria, who do not have risk factors for renal disease,
it is good practice to re-check the urine. Many patients, especially younger individuals, will
have transient proteinuria secondary to fever or intense exercise. These individuals should
be reassured that there is no renal pathology and that the proteinuria will resolve on its
own.
• Orthostatic proteinuria, which is characterized by increased excretion of protein at the
end of the day (i.e. following prolonged activities in upright position), is relatively common
in teenagers and usually resolves spontaneously. Here, also, reassurance that there is no
serious underlying pathology is key to management.
• Patients with isolated, asymptomatic persistent proteinuria usually excrete 1-2g/day.
These patients will need to be referred to nephrology and evaluated for an underlying
pathology. In cases where autoimmune disorders or malignancies are determined to be
the cause, involvement of specialist services is warranted.
• For patients with diabetes and/or hypertension, optimal management of these conditions
is paramount for treating the proteinuria. Use of angiotensin converting enzyme (ACE)
inhibitor or angiotensin receptor blocker therapy is indicated to prevent progression of
nephropathy. These patients should also be screened regularly for nephropathy with
urinalysis for microalbuminuria.

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