what is nephrotic syndrome?
Nephrotic syndrome: A
clinical complex characterized by a number of renal and extrarenal
features.
• The most prominent features
are
o Proteinuria of >3.5g per 24 hours
(in practice, >3.0 to 3.5 g per 24 h)
o hypoalbuminemia
o Edema
o Hyperlipidemia
o Lipiduria
o Hypercoagulability
• It should be stressed that the
key component is proteinuria which results from altered
permeability of the glomerular
filtration barrier for protein.
• The other components of the
Nephrotic syndrome and the ensuing metabolic
complications are all secondary to
urine protein loss and can occur with lesser degrees of
proteinuria or may be absent even in
patients with massive proteinuria.
Causes
of Nephrotic Syndrome
• There are many specific causes
of nephrotic syndrome.
• In all cases injury to
glomeruli is an essential feature.
• Nephrotic syndrome may affect
adults and children of both sexes and of any race.
• It may occur in typical form
or in association with nephritic syndrome.
• The latter connotes glomerular
inflammation with hematuria and impaired kidney
function.
Primary Causes of nephrotic syndrome
o
Minimal-change nephropathy
o
Focal glomerulosclerosis
o
Membranous nephropathy
o Hereditary nephropathies
either primary and or secondary causes.
Secondary Causes
• Being a renal manifestation of a
systemic general illness
o
Diabetes mellitus (DM)
o
Systemic lupus erythematosus (SLE)
o
Amyloidosis and paraproteinemias
o
Viral infections (e.g. hepatitis B,
hepatitis C, HIV)
o
Pre-eclampsia
Other Causes
• Medication can cause nephrotic
syndrome.
• This includes the very infrequent
occurrence of minimal-change nephropathy with
NSAID
use i.e aspirin and the occurrence of membranous nephropathy with the
administration of
gold
and penicillamine which are older drugs used for rheumatic diseases.
Pathophysiology
• Proteinuria that is more than 85%
albumin is selective proteinuria.
• Albumin has a net negative charge and
it is proposed that loss of glomerular membrane
negative
charges could be important in causing albuminuria.
• Nonselective proteinuria being a
glomerular leakage of all plasma proteins would not
involve
changes in glomerular net charge but rather a generalized defect in
permeability.
• This construct does not permit
clear-cut separation of causes of proteinuria except in
minimal-change
nephropathy in which proteinuria is selective.
Pathogenesis of Oedema
• An increase in glomerular permeability
leads to albuminuria and eventually to
hypoalbuminemia.
• In turn hypoalbuminemia lowers the
plasma colloid osmotic pressure causing greater
transcapillary
filtration of water throughout the body and thus the development of edema
Metabolic Consequences of
Proteinuria
• In
nephrotic syndrome levels of serum lipids are usually elevated.
• The
loss of antithrombin III and plasminogen via urine along with the simultaneous
increase
in clotting factors especially factors I, VII, VIII and X increases the risk
for
venous
thrombosis and pulmonary embolism.
• Vitamin
D binding protein may be lost in the urine leading to hypovitaminosis D with
malabsorption
of calcium and development of bone disease.
• Urinary
immunoglobulin losses may lower the patient's resistance to infections and
increase
the risk of infections.
Clinical Features of Nephrotic
Syndrome
History
• The
first sign of nephrotic syndrome in children is usually swelling of the face
followed
by
swelling of the entire body.
• Adults
can present with dependent edema.
• Foamy
urine may be a presenting feature.
• A
thrombotic complication such as deep vein thrombosis of the calf veins or even
a
pulmonary
embolus may be the first clue indicating Nephrotic syndrome.
• Additional
historical features that appear can be related to the cause of Nephrotic
syndrome.
• Recent
start of a non steroidal anti-inflammatory drug (NSAID) or a 10-year history of
diabetes
may be very relevant.
Physical
• Edema
is the predominant feature of nephrotic syndrome and initially develops around
the
eyes and legs.
• With
time edema becomes generalized and may be associated with an increase in weight
and
development of ascites or pleural effusions.
• Haematuria
and hypertension manifest in a minority of patients.
• Additional
features on exam will vary according to the cause and as a result of whether or
not
renal function impairment exists.
• In
cases of longstanding diabetes there may be diabetic retinopathy which
correlates
closely
with diabetic nephropathy.
• If the
kidney function is reduced there may be hypertension and/or anemia
Differential Diagnoses
• Diabetic
nephropathy
• Focal
segmental glomerulosclerosis
• Glomerulonephritis
• HIV
nephropathy
• IgA
nephropathy
• Minimal
change kidney disease
• Light
chain-associated renal disorders
• Nephritis
• Radiation
• Sickle
cell nephropathy
• Heart
failure
• Liver
cirrhosis with portal hypertension
Investigations
• Perform
dipstick screening method for detection of protein concentrations in urine.
• The
dipstick is a quick method of screening and detecting proteinuria, hematuria,
and
pyuria
and provides an estimate of the specific gravity (urine-concentrating
capacity).
• More
laboratory investigations can be done at higher centers.
Laboratory Studies
• Urinalysis
is the first test used in the diagnosis of Nephrotic syndrome
• Nephrotic
range proteinuria will be apparent by 3+ or 4+ readings on the dipstick or by
semi
quantitative testing by sulfosalicylic acid
• A
3+ reading is 300 mg/dl of urinary protein or more which is 3 g/l or more and
thus in
the
Nephrotic range
• The
chemistry of the dipsticks is such that albumin is the major protein that is
tested
• The
urine sediment exam may show cells and/or casts
• The
presence of more than 2 red blood cells (RBCs) per high power field is
indicative of
microhematuria
• Urinary
protein is measured by a timed collection or a single spot collection
• In
healthy individuals there are no more than 150 mg of total protein in a 24-hour
urine
collection
• A
single spot urine collection is much easier to obtain
• Serum
tests for kidney function are essential
• Serum
creatinine will be in the normal range in uncomplicated nephrotic syndrome such
as
that occurring in minimal-change nephropathy
• The
serum albumin is classically low in nephrotic syndrome being below its normal
range
of
3.5-4.5 g/dl
Imaging Studies
• Ultrasonographic
Scanning
can be used to determine whether a patient possesses 2 kidneys and to
demonstrate
their echogenicity.
Note:
Individuals with a single kidney may be prone to developing focal
glomerulosclerosis.
Having only
one kidney is also a relative contraindication to kidney biopsy.
Treatment
• Acute
Management of Adult Nephrotic Syndrome
o
The principles for acute management of
adults with nephrotic syndrome are similar to
those
for children.
o
Diuretics will be needed such as
Furosemide, Spironolactone and even Metolazone
may
be used.
o
Volume depletion may occur with
diuretic use which should be monitored by
assessment
of symptoms, weight, pulse and blood pressure.
o
Anticoagulation has been advocated by
some for use in preventing thromboembolic
complications
but its use in primary prevention is of unproven value.
o
Hypolipidemic agents may be used but if
the nephrotic syndrome cannot be controlled
there
will be persistent hyperlipidemia.
o
In secondary Nephrotic syndrome such as
that associated with diabetic nephropathy,
angiotensin-converting
enzyme (ACE) inhibitors and/or angiotensin II receptor
blockers
are widely used.
Specific Treatment of Nephrotic
Syndrome
• Depends
on the disease's cause.
• Glucocorticosteroids
such as prednisone are used for minimal-change nephropathy.
• Prednisone
and cyclophosphamide are useful in some forms of lupus nephritis.
• Secondary
amyloidosis with Nephrotic syndrome may respond to anti-inflammatory
treatment
of the primary disease.
Diet
• For
patients with Nephrotic syndrome their diet should provide adequate energy
(caloric)
intake
and adequate protein (1-2 g/kg/d).
• Supplemental
dietary protein is of no proven value.
• A
diet with no added salt will help to limit fluid overload.
• Management
of hyperlipidemia could be of some importance if the Nephrotic state is
prolonged.
• Fluid
restriction per se is not required.
Activity
• There
are no activity restrictions for patients with Nephrotic syndrome
• Ongoing
activity rather than bed rest will reduce the risk of blood clots
Complications
• Infection
is a major concern in nephrotic syndrome.
• Atherosclerotic
vascular disease appears to occur in greater frequency in subjects with
nephrotic
syndrome than in healthy subjects of the same age.
• Hypocalcemia
is common in nephrotic syndrome but rather than being a true
hypocalcemia
it is usually caused by a low serum albumin level.
• Venous
thrombosis and pulmonary embolism are well known complications of nephrotic
syndrome.
• Hypovolemia
is generally observed only when the patient's serum albumin level is less
than
1.5 g/dl.
• Acute
renal failure may indicate an underlying glomerulonephritis but is more often
precipitated
by hypovolemia or sepsis.
• Hypertension
related to fluid retention and reduced kidney function may occur.
• Failure
to thrive (in children) may develop in patients with chronic edema including
ascites
and pleural effusion.
Prognosis
• The
prognosis for patients with primary nephrotic syndrome depends on its cause.
• The
prognosis with congenital nephrotic syndrome is poor and survival beyond
several
months
is possible only with dialysis and kidney transplantation.
• Only
about 20% of patients with focal segmental glomerulosclerosis undergo remission
of
proteinuria. An additional 10% improve but remain proteinuric.
• Many
patients experiencing frequent relapses become steroid-dependent or become
steroid-resistant.
• End-stage
renal disease develops in 25-30% of patients with focal segmental
glomerulosclerosis
(FSGS) by 5 years and in 30-40% of these patients by 10 years.
• The
prognosis for children with minimal-change nephropathy is very good.
0 comments:
Post a Comment