Proteinuria in Primary Care
·
Most sources consider 150 mg. per day to be upper limit of
normal.
·
Normal is usually below 100 mg. per day. Not all of this is albumin.
·
Measured as urinary albumin / creatinine ratio.
·
Albumin excretion usually less than 20 mg./day in
normals. Microalbuminuria lies in the
range of 30 – 300 mg. /day. Urine
dipstick will pick up levels higher than this as overt
proteinuria.
·
Albumin/creatinine ratio typically < 2.5 (variable with
gender and lab). Levels of 2.5-25 are
equivocal and require re-measurement.
·
Predictive of progression to renal disease in diabetics and
patients with hypertension or vascular disease.
·
Proteinuria at levels 300 mg. to 3 grams / day.
·
Usually detected by dipstick.
·
Requires investigation including history, physical,
assessment of renal function and consideration of renal ultrasound if at a
level of 2 – 3 grams / day.
·
If no systemic disease found and normal renal function, 50%
develop hypertension and 40% develop renal insufficiency over 20 years. Requires followup.
·
Proteinuria above 3 grams / day.
·
Requires treatment and nephrologist for several reasons:
·
Progressive renal disease is common.
·
Problems with edema secondary to low serum albumin and renal
sodium retention.
·
Accompanied by hyperlipidemia, hypertension and risk for
accelerated vascular disease
·
Primarily albumin. A
large protein which is filtered out by a normal glomerulus, thus implies
glomerular disease.
·
In glomerular disease there are fewer glomeruli. This provokes efferent arteriole
vasoconstriction via angiotensin resulting in higher filtration pressures
across the glomerulus. This in turn
results in further glomerular damage.
ACE inhibitors help to blunt this process.
·
Usually low molecular weight proteins such as light chains
and kappa chains, hemoglobin, myoglobin and Bence Jones proteins pass through
the glomerulus and are reabsorbed by normal renal tubules.
·
In presence of tubular disease these proteins are
incompletely absorbed leading to non-albumin proteinuria. This will be missed on dipstick,
which measures only albumin > 300 mg./day.
·
Progressive tubulointerstitial disease leads to progressive
nephron loss, glomerular hypertension, glomerular damage and albuminuria.
·
Over – filtration of small molecular weight proteins
overwhelms normal tubular reabsorption and they appear in the urine. These again will be missed on dipstick
testing.
·
Small molecular weight proteins produced by hemolysis (Hb),
rhabdomyolysis (myoglobin), kappa and light chains (myeloma or monoclonal
gammopathies). This category includes
Bence Jones proteins.
·
Presence of large amounts of such proteins is actually toxic
to the kidney leading to progressive renal disease if protein production is
massive or poorly controlled.
·
Does not appear in all classifications of proteinuria.
·
Includes proteins from tubular, ureteral and bladder cell
breakdown and arises distal to the glomerulus.
·
Usually less than 500 mg. / day.
·
Can imply presence of trauma, tumor, obstruction or stone.
·
Orthostatic proteinuria.
Detect by overnight 8 hour urine protein collection. Should be less than 50 grams.
·
Seen in high fever, extreme psychological stress and heavy
physical exercise.
·
Seen in congestive failure because of high angiotensin
levels.
1. Early detection
by albumin/creatinine ratio indicated:
·
Type 1 diabetics after 5 years
·
Type 2 diabetics and impaired fasting glucose / glucose
tolerance at diagnosis.
·
Hypertensives who are not diabetic.
·
Metabolic syndrome without
diabetes.
2. Early detection
in these patients can influence progression of renal disease.
1. Includes assessment of renal function, history, physical and
sometimes imaging.
2. Common scenarios:
·
Family history of renal disease
·
First Nations or Pacific Islands background.
·
Diagnosis often leading to renal disease such as SLE.
·
Symptoms or signs leading to suspicion such as back pain or
lytic lesion in an older patient suggesting myeloma.
·
Albumin only.
Insensitive to low molecular weight proteins.
·
Not positive until 300 mg./day excretion. Qualitative only
·
Falsely high in concentrated urine.
·
False positive in presence of iodinated contrast, sulfas and
high-dose penicillin.
·
Detects all proteins.
Semi-quantitative.
·
False positive with iodinated contrast.
·
This will detect light and kappa chains in myeloma.
·
Quantitative test measures all proteins in the urine
·
Probably indicated if persistent dipstick albumin along with
exam and assessment of renal function.
·
Urinary quantitative test for screening for early disease in
diabetes and hypertension with and without vascular disease.
·
Test to assess proteinuria < 3 grams/day found in
patients under 30 with normal renal function.
Detects orthostatic proteinuria, which tends to be a benign condition.
·
If overnight urine protein < 50 mg. diagnosis of
orthostatic proteinuria is made.
·
Most proteinuria is an incidental finding or is a result of
appropriate case finding. This has to
be followed by directed history and physical and repeat urinalysis with exam of
urinary sediment.
·
If qualitative urinalysis remains positive, 24 hour
quantitative assessment must be done together with creatinine and urea.
·
Proteinuria > 3 grams/day in nephrotic range requires
CBC, albumin, total protein and serum and urine protein electrophoresis. Renal ultrasound is helpful. Nephrology consult is indicated.
·
Proteinuria < 3 grams/day in a patient under 30 mandates
an 8-hour overnight urinary protein to detect orthostatic
proteinuria.
·
Proteinuria > 3 grams/day is usually glomerular disease,
however urine and serum protein electrophoresis should be done to exclude
myeloma.
·
Clinical signs and symptoms to suggest renal disease or myeloma in an older patient
with dipstick negative urine should prompt sulfosalicylic acid testing to
detect tubular or overflow proteinuria.
If present, urine and serum electrophoresis should follow.
·
Prior exposure to iodinated contrast, sulfas or high dose
penicillin suggest false positive result.
The test should be repeated when exposure is terminated.
·
Concurrent high fever, psychological stress, vigorous
physical exercise or untreated CHF suggest transient proteinuria. The test should be repeated when the
conditions have stabilized.
·
Proteinuria < 50 grams on an 8 hour collection overnight
in a young person suggests orthostatic proteinuria.
Proteinuria
detected
History and
Physical
Exam of
urinary sediment
Manage
according to diagnosis if clear
Nephrology
consult for glomerular disease
Repeat
qualitative proteinuria test
Measure
urea, creatinine, 24 hour urine protein
Abnormal renal function tests or
Transient
proteinuria. Reassure patient
Split urine
test – 8 hour overnight
urine
protein
Orthostatic proteinuria.
Reassure patient.
Renal
ultrasound. Refer to Nephrologist
CBC, total
protein, albumin, serum and urine
electrophoresis,
renal ultrasound
Nephrology
referral
Table 4.
Clinical identification of the metabolic syndrome* using NCEP ATPIII criteria
|
Risk Factor |
Defining Level |
|
FPG |
>/=
6.1 mm/L |
|
BP |
>/+
130/85 |
|
TG |
>/=
1.7 mm/L |
|
HDL-C Men Women |
<1.0
mm/L <1.3
mm/L |
|
Abd.
Obesity Men Women |
Waist
Circ. >102
cm. >88
cm. |
*A diagnosis of metabolic syndrome is
made when 3 or more of the risk determinants are
present.
1.
Audio Digest Family Practice Vol 38(30) Aug 6, 1990.
2.
UpToDate ver. 14.2
2006. Topics in Nephrology.
3.
Craven NH. Management of chronic kidney disease in the primary
care setting. B.C. Medical Journal 2005; 47(6): 296-299.
4.
Chen B. Combination
treatment effective option for hypertensive, diabetic patients with
microalbuminuria. CMAJ 2001: 164(6): 861.
5.
B.C. Guidelines and Protocols for Chronic Kidney Disease, 2004.
6.
B.C. Guidelines and Protocols for Diabetes Care, 2004.