- Nephrotic syndrome is defined as protein excretion greater than 3.5 g/24 hours, hypoalbuminemia less than 3.0 g/dL, and peripheral edema. - Common causes include minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy. Secondary causes can be due to diseases like diabetes, lupus, amyloidosis. - Metabolic consequences of nephrotic syndrome include hyperlipidemia, risk of infection due to urinary protein losses, hypocalcemia, hypercoagulability, and hypovolemia with severe hypoalbuminemia.

1. • Nephrotic Syndrom
nephrotic = protein
nephritic = blood
- few RBC in nephrotic syndrome
- nephritic syndrome: more than 1 gram means its nephrotic nephritic
protein in the urine= bad prognosis- means the kidney is sick
INTRODUCTION
AMOUNTS OF PROTEINURIA — In normal subjects, low molecular weight proteins
and small amounts of albumin are filtered. no more than about 2 to 4 g of albumin per
day are filtered normally, each day (with the bulk of this filtered albumin "reclaimed" in
the early proximal tubule). The filtered proteins enter the proximal tubule where they
are almost completely reabsorbed and then catabolized by the proximal tubular cells.
Some of the catabolized proteins (including albumin) are excreted as peptides in the
urine.. The net result is the normal daily protein excretion of less than 150 mg
(usually 40 to 80 mg), of which approximately about 4 to 7 mg is intact,
immunoreactive albumin.

2. TYPES OF PROTEINURIA — There are three basic types of proteinuria:
— Glomerular
— , tubular,
— overflow
Only glomerular proteinuria (ie, albuminuria) is identified on a urine dipstick
Glomerular proteinuria — Glomerular proteinuria is due to increased filtration of
macromolecules (such as albumin) across the glomerular capillary wall. The
proteinuria associated with diabetic nephropathy and other glomerular diseases, as
well as more benign causes such as orthostatic or exercise-induced proteinuria
fall into this category.
Tubular proteinuria — Low molecular weight proteins — such as ß2-
microglobulin, immunoglobulin light chains, retinol-binding protein, and amino

3. acids — have a molecular weight that is generally under 25,000 in comparison
to the 69,000 molecular weight of albumin. These smaller proteins can be filtered
across the glomerulus and are then almost completely reabsorbed in the proximal
tubule. Interference with proximal tubular reabsorption, due to a variety of
tubulointerstitial diseases or even some primary glomerular diseases, can lead to
increased excretion of these smaller proteins
Tubular proteinuria is often not diagnosed clinically since the dipstick for protein
does not detect proteins other than albumin and the quantity excreted is relatively
small
Overflow proteinuria — Increased excretion of low molecular weight proteins can
occur with marked overproduction of a particular protein, leading to increased
glomerular filtration and excretion. This is almost always due to immunoglobulin light
chains in multiple myeloma, but may also be due to lysozyme (in acute
myelomonocytic leukemia), myoglobin (in rhabdomyolysis), or hemoglobin (in
intravascular hemolysis) .In these settings, the filtered load is increased to a level
that exceeds the normal proximal reabsorptive capacity.
Patients with myeloma kidney also may develop a component of tubular proteinuria,
since the excreted light chains may be toxic to the tubules, leading to diminished
reabsorption.
In addition, patients with multiple myeloma and Bence Jones proteinuria can
also develop nephrotic syndrome due to AL (primary) amyloidosis.
MEASUREMENT OF URINARY PROTEIN
Standard urine dipstick — The standard urine dipstick primarily detects albumin via a
colorimetric reaction between albumin and tetrabromophenol blue producing
different shades of green according to the concentration of albumin in the sample.
Proteinuria on the urine dipstick is graded from 1+ to 4+, which reflects progressive
increases in the urine albumin concentration:

4. • Negative
• Trace — between 15 and 30 mg/dL - 1500 cc = 300 mg/24h
• 1+ — between 30 and 100 mg/dL –1500cc = 1.5gr/24h
• 2+ — between 100 and 300 mg/dL – 1500cc= 4.5gr/24h
• 3+ — between 300 and 1000 mg/dL –1500cc 3gr 10gr/24h
• 4+ — >1000 mg/dL-1500cc >10gr/24h
The urine dipstick is highly specific, but not very sensitive for the detection of mild
proteinuria; it becomes positive only when protein excretion exceeds 300 to 500
mg/day
Sulfosalicylic acid test — In contrast to the urine dipstick, which primarily detects
albumin, sulfosalicylic acid (SSA) detects all proteins in the urine( light chains)in MM
lyzozymes in AMN Leukemia
***the stick measures only albumin
A concentrated urine will overestimate and dilute urine, for example, will
underestimate the degree of proteinuria.
Measurement of quantitative protein excretion

5. Normal rate (albumin): up to 30mg/24h
Microalbuminuria : between 30 and 300 mg/day
Proteinuria : >300mg/24h
more than 3.5 grams per day = NEPHROTIC SYNDROME
- diabetics: disease that cause proteinuria- usually for first 10 yrs- doesnt
matter waht type- will have microalbuminuria- then will go to proteinuria,and
then nephrotic syndrome (more than 3.5 g /day)
- microalbuminuria: bad prognostic sign- we are about albumin- not total
proteinuria (unless pt has myeloma)
24-hour collection — The traditional method requires a 24-hour urine collection to
directly determine the daily total protein or albumin excretion. An extra benefit of this
approach, if creatinine is also measured, is that it provides the information necessary
to estimate the glomerular filtration rate (GFR) from the creatinine clearance.
Protein/creatinine ratio
An alternative method requires only a random urine specimen to estimate the degree
of proteinuria [9-12]. This test calculates the total protein-to-creatinine ratio (mg/mg).
This ratio correlates with daily protein excretion expressed in terms of g per 1.73m2 of
body surface area (figure 1). Thus, a ratio of 4.9 (as with respective urinary protein
and creatinine concentrations of 210 and 43 mg/dL) represents a daily protein
excretion of approximately 4.9 g per 1.73.
Thus, a ratio of 4.9 represents a daily protein excretion of approximately 4.9 g/
24h
- most imp test to detect early stage of renal disease: especially in diabetics
ACR Urine albumin to creatinine ratio — The urine albumin:creatinine ratio
(ACR), like the PC ratio, is measured using a random "spot" urine specimen.
The K/DOQI guidelines note that the relative merits of measuring and monitoring the
total protein-to-creatinine ratio versus the albumin-to-creatinine ratio to detect and
monitor kidney damage are unclear. However, given that albuminuria is a more

6. sensitive marker than total protein for chronic kidney disease due to diabetes,
hypertension, and glomerular diseases, they recommend, in adults, that the
ratio in spot urine samples should be measured with the albumin-to-creatinine
ratio. If the albumin-to-creatinine ratio is high (>500 to 1000 mg/g, which
corresponds to urinary albumin excretion of >500 to 1000 mg/day), they state
that total protein-to-creatinine ratio is also acceptable.
Types of proteinuria
Isolated proteinuria Proteinuria may be associated with a renal or systemic
disease, or it may be isolated. The latter occurs in asymptomatic patients without
evidence of any disease or abnormality of the urine sediment.it has, with a
favorable-to-excellent prognosis Most patients with benign causes of
isolated proteinuria excrete less than 1 to 2 g/day.
Proteinuria in pregnancy
In non-pregnant individuals, abnormal total protein excretion is typically defined as
greater than 150 mg daily. In normal pregnancy, urinary protein excretion increases
substantially, due to a combination of increased glomerular filtration rate and
increased permeability of the glomerular basement membrane Hence, total protein
excretion is considered abnormal in pregnant women when it exceeds 300 mg/
24 hours. Preeclampsia is the most common cause of proteinuria in pregnancy
and must be excluded in all women with proteinuria first identified after 20
weeks of gestation. If preeclampsia is excluded, then the presence of primary or
secondary renal disease should be considered
orthostatic or postural proteinuria In this disorder, which is primarily a disease
of adolescents, protein excretion is increased in the upright position but is normal when
the patient is supine. Thus, since the results of a random specimen vary markedly with
posture, a first morning spot urine can be obtained to help avoid this
confounding effect. A normal value in the first morning spot urine and dipstick-

7. positive proteinuria on an upright specimen is strongly suggestive of orthostatic
proteinuria
• Nephrotic Syndrome
• Definition
• protein excretion greater than 3.5 g/24 hours),
• hypoalbuminemia (less than 3.0 g/dL),
• peripheral edema.
• Hyperlipidemia
Isolated heavy proteinuria without edema or other features of the nephrotic syndrome
is suggestive of a glomerulopathy (with the same etiologies as the nephrotic
syndrome), but is not necessarily associated with the multiple clinical and management
problems characteristic of the nephrotic syndrome. This is an important clinical
distinction because heavy proteinuria in patients without edema or hypoalbuminemia is
more likely to be due to secondary focal segmental glomerulosclerosis
ETIOLOGY — Heavy proteinuria and the nephrotic syndrome may occur in association
with a wide variety of primary and systemic diseases. Minimal change disease is the
predominant cause in children. In adults, approximately 30 percent have a
systemic disease such as diabetes mellitus, amyloidosis, or systemic lupus
erythematosus; the remaining cases are usually due to primary renal disorders such
as membranous nephropathy minimal change disease, focal segmental
glomerulosclerosis.
A study of 233 renal biopsies performed between 1995 and 1997 at the University of
Chicago in adults with full-blown nephrotic syndrome (in the absence of an obvious
underlying disease such as diabetes mellitus or lupus) found the major causes to be
1.membranous nephropathy and focal segmental glomerulosclerosis (33 percent
each),
2.minimal change disease (15 percent),
3. amyloidosis (4 percent overall, but 10 percent in patients over age 44)
Over time, the relative frequency of membranous nephropathy fell from 38 to 15
percent, while the frequency of focal segmental glomerulosclerosis increased from
14 to 25 percent overall; this increase was primarily seen in black and Hispanic
patients.
Primary causes of nephrotic syndrome include the following, in
approximate order of frequency:
• Minimal-change nephropathy
• Focal Segmental glomerulosclerosis ( FSGS)
• Membranous nephropathy
Secondary causes include the following, again in order of approximate
frequency:

8. • Diabetes mellitus
• Lupus erythematosus
• Amyloidosis and paraproteinemias (MM)
• Viral infections (eg, hepatitis B, hepatitis C, human
immunodeficiency virus [HIV] )
• Preeclampsia
Metabolic consequences of proteinuria
Metabolic consequences of the nephrotic syndrome include the following:
Infection
Urinary immunoglobulin losses
• Edema fluid acting as a culture medium
• Protein deficiency
• Decreased bactericidal activity of the leukocytes
• Immunosuppressive therapy
• Decreased perfusion of the spleen caused by hypovolemia
• Urinary loss of a complement factor (properdin factor B) that
opsonizes certain bacteria
•
• Hyperlipidemia and atherosclerosis
• It is related to the hypoproteinemia and low serum oncotic pressure
of nephrotic syndrome, which then leads to reactive hepatic protein
synthesis, including of lipoproteins.[7] In addition, reduced plasma
levels of lipoprotein lipase results in diminution of lipid catabolism
• Hypocalcemia and bone abnormalities
•
Hypocalcemia is common in the nephrotic syndrome, but rather than
being a true hypocalcemia, it is usually caused by a low serum
albumin level.
Nonetheless, low bone density and abnormal bone histology are reported
in association with nephrotic syndrome. This could be caused by urinary

9. losses of vitamin D–binding proteins, with consequent hypovitaminosis D
and, as a result, reduced intestinal calcium absorption.[9]
•
• Hypercoagulability
Venous thrombosis and pulmonary embolism are well-known
complications of the nephrotic syndrome. Hypercoagulability in these
cases appears to derive from urinary loss of anticoagulant proteins, such as
antithrombin III and plasminogen, along with the simultaneous increase
in clotting factors, especially factors I, VII, VIII, and X.
•
• Hypovolemia
•
• Hypovolemia occurs when hypoalbuminemia decreases the plasma
oncotic pressure, resulting in a loss of plasma water into the
interstitium and causing a decrease in circulating blood volume.
Hypovolemia is generally observed only when the patient's serum
albumin level is less than 1.5 g/dL