1.Pathophysiology of Edema.

Edema is generally defined as an increase in ISF palpable swelling,

pitting or nonpitting; in most cases, it is first detected in the lower
extremities.
Generalized edema usually becomes clinically apparent when ECF
expands by about 5 L = 10-lb weight gain due to sodium and water
retention.
Localized edema is more likely to be nonpitting and is typically caused by a
focal obstructive or inflammatory process. The balance of hydrostatic and
oncotic pressure in the vascular system and interstitial space creates an
environment that allows normal movement of water and diffusible solutes
from the vascular space at the arteriolar end of the capillaries and a return at
the venous end by way of the lymphatics.
CAUSES: vascular hydrostatic pressure, vascular oncotic
pressure, or some local process obstructing venous or lymphatic
return.
Cardiac: usually R-heart failure, late in heart disease; gravity-dependent
(first noted in the feet and ankles). MCC of cardiac edema is CHF d/t
systolic or diastolic dysfunction. CO = plasma volume and
activation of renin-angiotensin systems = renal vasoconstriction
and Na/H2O retention = capillary hydrostatic pressure.
Constrictive pericarditis and pulmonary hypertension can also cause
edema by decreasing cardiac output and activating the same
mechanisms.
Hepatic: MCC of hepatic edema in patients with liver disease is
cirrhosis. Portal systemic pressure d/t obstruction of hepatic
venous outflow caused by hepatic damage. venous return =
arterial blood volume = Na/H2O retention. plasma oncotic
pressure d/t cirrhosis-related hypoalbuminemia further
exacerbates this process and combines to stimulate the reninangiotensin-aldosterone system resulting in additional sodium and
water retention. Ascites, fluid accumulation in the peritoneal cavity, is
the hallmark of cirrhosis-related edematous patients; however, in
advanced cirrhosis generalized edema may develop, particularly
when serum albumin is <3.5 mg/dL. Tense abdominal ascites may
increase intra-abdominal pressure, decreasing venous return from the
lower extremities and further worsening lower extremity edema.
Renal: Edema is a common physical finding in patients with chronic
renal insufficiency. At first, GFR = renal retention of Na/H2O
through stimulation of the renin-aldosterone system. In ESRD, oliguria
and anuria prevents renal elimination of water. Patients with
acute glomerulonephritis and nephrotic syndrome may also be
edematous; however, they are likely to have larger amounts of

proteinuria and worse secondary hypoalbuminemia as a cause of

the edema.
Medications: undesirable SE. Vasodilating antihypertensives,
including calcium channel blockers and direct vasodilators such as
hydralazine, most likely to cause peripheral edema. The
dihydropyridine calcium channel blockers including nifedipine and
amlodipine appear to be more likely than other calcium channel
blockers to cause edema. estrogens, testosterone, and
corticosteroids have been shown to cause peripheral edema,
most likely due to vasodilatation or increased sodium and water
retention. NSAIDs inhibit prostaglandins = deterioration in renal
function through renal vasoconstriction and increased sodium
retention, which leads to increased edema, particularly in
patients with cirrhosis or chronic renal insufficiency.
Nutritional Deficiency: Hypoalbuminemia d/t severe protein
malnutrition. Protein-losing enteropathy and other malabsorptive
states such as chronic pancreatitis, which lead to serum albumin
<3.5 mg/dL, are potential causes.
Myxedema: Hypothyroidism (Chapter 66) causing myxedema is a
common cause of nonpitting edema. Myxedema is typically noted in the
pretibial region and may sometimes be associated with periorbital
puffiness. Patients demonstrating myxedema may also have other
manifestations of hypothyroidism including cognitive impairment,
coarsening of hair, bradycardia, fatigue, dyspnea, constipation, and
depression. Idiopathic Edema
Idiopathic edema is a clinical syndrome occurring most commonly
among women. In many patients, it is associated with abdominal
distension and diurnal variations in weight that may vary by several
pounds from morning to evening. The most likely cause is increased
capillary permeability; however, there may be some contribution
from chronic stimulation of the renin-angiotensin-aldosterone
system. This syndrome differs from the cyclic edema experienced
by many women related to estrogen-induced sodium and water
retention. In some cases, the use of diuretics can exacerbate the edema
by causing mild hypovolemia and further renin stimulation.
Localized Edema: The differential diagnosis of localized edema includes
obstructive processes causing limb edema and inflammatory processes
causing increased capillary permeability and localized edema of a
different nature. In most cases, this edema is nonpitting. venous or
lymphatic, include venous insufficiency due to DVT or more
superficial thrombophlebitis, lymphadenopathy or pelvic masses
inhibiting lower extremity venous return, congenital or primary
lymphatic obstruction, and neoplasm with surgery- and radiationassociated inflammatory changes that impede lower extremity
venous return. Infectious diseases such as lymphangitis and

filariasis are also known to cause limb edema. Other causes of

localized edema that do not appear to involve an entire limb include
burns, cellulitis, and angioedema. Inflammation due to infection or
other tissue injury causes increased capillary permeability and
interstitial edema. In such patients, the edema is usually nonpitting and
the history and visible erythema suggest these diagnoses.
2. List a differential diagnosis for nephrotic syndrome
Many disorders can cause glomerular damage and lead to nephrotic
syndrome. The following medical conditions account for most cases of
nephrotic syndrome:
Minimal change disease. The most common cause of nephrotic
syndrome in children, this disorder results in abnormal kidney function,
but when the kidney tissue is examined under a light microscope, it
appears normal or nearly normal. The cause of the abnormal function
typically can't be determined.
Focal segmental glomerulosclerosis. Characterized by scattered
scarring of some of the glomeruli, this condition may result from
another disease, a genetic defect, hypertensive nephrosclerosis, HIV or
is idiopathic.
Membranous nephropathy. This kidney disorder is the result of
thickening membranes within the glomeruli. The exact cause of the
thickening isn't known, but it's sometimes associated with other
medical conditions, such as hepatitis B, malaria, cancer, Sjgren's
syndrome, sarcoidosis, syphilis or drugs.
Diabetic kidney disease. Diabetes can lead to kidney damage that
affects the glomeruli, particularly in people with diabetes that's poorly
controlled.
Systemic lupus erythematosus. This chronic inflammatory disease can
lead to serious kidney damage.
Amyloidosis. This disorder occurs when substances called amyloid
proteins accumulate in your organs. Amyloid buildup often affects the
kidneys, damaging their filtering system.
3. Contrast nephrotic and nephritic syndromes
Nephotic syndrome is characterized by proteinuria (>3.5g/day),
hypoalbuminemia, hyperlipidemia (elevated lipoproteins and chol)
and edema (periorbital). Edema can present several ways, such as
puffiness around the eyes, pitting edema over the legs, fluid in the pleural
cavity causing pleural effusion or fluid in the peritoneal cavity causing
ascites. In addition, some patients may notice foamy urine, due to a
lowering of the surface tension by the severe proteinuria. Actual urinary
complaints such as hematuria or oliguria are uncommon, and are seen

commonly in nephritic syndrome. May have features of the underlying

cause, such as the rash associated with Systemic Lupus Erythematosus, or
the neuropathy associated with diabetes.
Nephritic syndrome is characterized by hematuria with red blood cell casts
in the urine, mild hypertension, uremia due to retention of waste products
and variable renal insufficiency with azotemia (elevated blood nitrogen) and
oliguria. The proteinuria in nephritic syndrome is not usually severe, but
may occasionally be heavy enough to be in the range usually found in
nephrotic syndrome. Mnemonic: PHAROH = Proteinuria, Hematuria,
Azotemia, RBC casts, Oliguria, Hypertension
4. Describe the evaluation of the juvenile and adult patient with
nephrotic syndrome.
ADULTS
A careful medical history may reveal a cause for proteinuria, such as
diabetes mellitus or a prior history of renal disease. Poststreptococcal
glomerulonephritis, for example, may be associated with persistent
proteinuria years after recovery from the acute episode, a possible reflection
of some irreversible glomerular damage.
Examination of the urine Examination of the urine is important in all
patients with proteinuria. The urine sediment should be examined, looking
for other signs of glomerular disease such as hematuria, red cell casts, or
lipiduria. Red cell casts, for example, are virtually pathognomonic for
glomerulonephritis. If the sediment is unremarkable, the differential
diagnosis includes transient proteinuria, orthostatic proteinuria, and
persistent proteinuria. The urine dipstick should be repeated on at least one
other visit. If these subsequent tests are negative for protein, the likely
diagnosis is transient proteinuria.
Rule out transient proteinuria Transient proteinuria is by far the most
common, occurring in 4 percent of men and 7 percent of women on a single
examination, with resolution on subsequent examinations in almost all
patients. A transient increase in protein excretion may be seen with fever
and exercise, perhaps mediated by angiotensin II or norepinephrine-induced
alterations in glomerular permeability, as well as with symptomatic urinary
tract infection. With marked exercise, for example, protein excretion can
exceed 1.5 mg/min in normal subjects (which is the equivalent of over 2
g/day if sustained). The excretion of both albumin and low molecular weight
proteins is increased, suggesting both an increase in glomerular permeability
(to allow the filtration of albumin) and a reduction in proximal reabsorption
(to permit the excretion of normally filtered smaller proteins; see below).
These patients need no further evaluation and should be reassured that they
do not have kidney disease.
Rule out orthostatic proteinuria A split urine collection should be
obtained if the patient is younger than age 30 and has documented
proteinuria on more than one occasion. This test detects orthostatic

proteinuria, a relatively common finding in adolescents (occurring in 2 to 5

percent), but an uncommon disorder in those over the age of 30. Orthostatic
proteinuria is characterized by increased protein excretion in the upright
position, but normal protein excretion when the patient is supine. The
mechanism by which orthostatic proteinuria occurs is unclear, but
neurohumoral activation and altered glomerular hemodynamics may be
important. Total protein excretion is generally less than 1 g/day in orthostatic
proteinuria, but may exceed 3 g/day in selected patients. Orthostatic
proteinuria is a benign conditions requiring no further evaluation or specific
therapy. In many patients, the condition resolves over time.
Split urines are collected according to the following protocol
The first morning void is discarded.
A 16-hour upright collection is obtained between 7 AM and 11 PM, with
the patient performing normal activities and finishing the collection by
voiding just before 11 PM. (The times can be adjusted according to the
normal times at which the patient awakens and goes to sleep.)
The patient should assume the recumbent position 2 hours before the
daytime collection is finished to avoid contamination of the supine
collection with urine formed when in the upright position.
A separate overnight 8 hour collection is obtained between 11 PM and
7 AM.
Instead of the cumbersome 24-hour urine collection, the protein-to-creatinine
(Pr/Cr) ratio may be used on a first morning spot urine specimen and on a
specimen collected while upright. For this, the patient is instructed to void
before going to bed and to remain recumbent until the first morning sample
is obtained. A normal Pr/Cr ratio on the first morning void and dipstickpositive proteinuria with an elevated Pr/Cr ratio on a second specimen
collected while the patient is upright indicates orthostatic proteinuria.
Many patients with glomerular disease will have a modest reduction in
protein excretion when supine. However, the diagnosis of orthostatic
proteinuria requires that protein excretion be normal when supine (less than
50 mg per 8 hours), not merely less than when in the upright position.
Persistent proteinuria Persistent proteinuria usually reflects an
underlying renal or systemic disorder. As an example of a systemic disorder,
heart failure is often associated with mild proteinuria that may be mediated
by persistent increases in angiotensin II and norepinephrine. Other patients
have an underlying glomerular disease that may be primary (focal
glomerulosclerosis or membranous nephropathy) or secondary (diabetic
nephropathy or benign nephrosclerosis due to systemic hypertension). A
thorough evaluation is warranted when proteinuria persists with a normal
urine sediment. Renal function tests (blood urea nitrogen, creatinine) should
be ordered, as well as a quantitative measurement of urine protein excretion.
The patient should be referred to a nephrologist for further evaluation (eg,
renal biopsy) and possible therapy.
Radiologic examination and nephrology referral Patients whose
persistent proteinuria is not explained by postural change should undergo an

ultrasound examination to rule out structural causes, such as reflux

nephropathy or PCKD. Regardless of the presence or absence of structural
abnormalities, those with persistent proteinuria should be referred to a
nephrologist for decisions regarding further management (eg, renal
biopsy). A renal biopsy is performed if there is some sign of severe or
progressive disease, such as nephrotic syndrome, increasing protein
excretion, or an elevation in the plasma creatinine concentration. In one
prospective study, for example, a management decision was changed after
renal biopsy in only three of 25 patients with isolated non-nephrotic
proteinuria. We and most other nephrologists also perform a biopsy in
patients with somewhat higher degrees of non-nephrotic proteinuria (2 to 3
g/day). If such a patient is reluctant to undergo biopsy, absolute indications
include increasing proteinuria or plasma creatinine concentration, or a
significant elevation in blood pressure over baseline values.
CHILDREN
Asymptomatic child The diagnostic evaluation of the child with dipstickpositive proteinuria depends in part upon the presence or absence of
symptoms. In the asymptomatic child with an incidentally discovered positive
dipstick for proteinuria, the first step is to repeat the test since, as
mentioned above, the great majority of such episodes are transient and do
not reflect any renal disease. The simplest approach is to measure the Pr/Cr
ratio on a first morning void obtained at home, and to send for
urinalysis a second specimen obtained in the office. The parents should be
instructed to have the child void before going to bed and to remain
recumbent until the first morning sample is obtained.
The following findings may be obtained:
A normal Pr/Cr ratio on the first morning void + normal
urinalysis indicate transient proteinuria.
A normal Pr/Cr ratio on the first morning void + dipstickpositive proteinuria on the second upright specimen indicate
orthostatic proteinuria.
If the proteinuria is transient or orthostatic, the patient should have a repeat
urinalysis on a first morning void in one year.
An elevated Pr/Cr ratio on the first morning void + positive
dipstick on the second specimen indicate persistent
proteinuria that requires further evaluation, beginning with
examination of the urine sediment, looking for other signs of
glomerular and/or parenchymal disease such as hematuria, red cell
casts, pyuria, and/or lipiduria. Red cell casts are pathognomonic for the
presence of glomerulonephritis. Based upon the particular findings,
certain patterns on the urinalysis are suggestive of glomerulonephritis,
nephrotic syndrome, or other renal parenchymal disorders.
The urinalysis may also be suggestive of a urinary tract infection with pyuria,
bacteriuria, and positive nitrites or leukocyte esterase along with mild

proteinuria. Proteinuria in such children typically resolves with

successful treatment of the infection. If the proteinuria persists after
eradication of the infection, further work-up is indicated.
Among children with persistent proteinuria, a complete history and physical
examination should be reviewed, including measurement of the blood
pressure. Initial laboratory evaluation includes renal function tests (blood
urea nitrogen and creatinine), serum electrolytes, cholesterol,
albumin, and total protein. Other tests such as renal ultrasound,
serum complement levels (C3 and C4), ANA, streptozyme testing,
hepatitis B and C serology, and HIV testing should be considered if
appropriate. A voiding cystourethrogram should be considered if there is an
abnormal ultrasound with scarring or a history of febrile urinary tract
infections.
If this initial evaluation is normal, the urine dipstick should be repeated on at
least two additional specimens. If these subsequent tests are negative for
protein, the diagnosis is transient proteinuria.
If the proteinuria persists or if any of the studies are abnormal, the patient
should be referred to a pediatric nephrologist. At this point, urinary
protein excretion should be quantified by a timed collection, if obtainable.
Indications for renal biopsy The role of renal biopsy in a child with isolated
asymptomatic persistent proteinuria is controversial. Many nephrologists
recommend close monitoring for those children with urinary protein excretion
below 500 mg/m2 per day before considering a biopsy. Monitoring should
include assessment of blood pressure, protein excretion, and renal function.
If any of these parameters shows evidence of progressive disease, a renal
biopsy should be performed to establish a diagnosis.

5. Distinguished between minimal charge disease and focal

sclerosing glomerulonephritis.
Minimal Change Disease (GOOD PROGNOSIS) is the MCC of nephrotic
syndrome in children (2-6 yr). It is characterized by diffuse effacement
of foot processes of epithelial cells in the glomeruli (changing
charge that allows protein to come through). Appear normal by LM
and IF! It sometimes follows a respiratory infection or routine
prophylactic immunization with its most characteristic feature being is
dramatic response to corticosteroid therapy. The cause of MCD is
still unclear, but while there is an absence of immune deposits in the
glomerulus it is thought to be some sort of immune dysfunction due to
some of its presenting characteristics (association w/ resp. infections,
response to steroids, associations with atopy (skin hypersensitivity), higher
incidence in those with Hodgkin disease whose association with T-cell defects
has been documented). Glomerulus will show a normal basement
membrane with absence of proliferation. The main thing that can be seen by
electron microscoy is in the visceral epithelial cells which show a

uniform and diffuse effacement of foot processes. Clinical

presentation will see massive proteinuria while renal function remains
good. The proteinuria is highly selective w/ most of the protein being
albumin. As stated before there is usually a dramatic response to
corticosteroids. Long term prognosis is excellent.
Focal Semental Glomerulosclerosis (BAD PROGNOSIS & seen in
morbidly obese pts.) is characterized by sclerosis of some, but not all,
glomeruli (focal) and in the affected glomeruli only a portion of the
capillary tuft is involved (segmental). Nephrotic syndrome is often seen
with it. It is the MCC of nephrotic syndrome in adults (esp. Hispanic
and African Americans), and HIV pts (HIV-associated neuropathy).
The clinical signs differ from minimal change disease in the flowing
ways:

Higher incidence of hematuria, reduced GFR and hypertension

Proteinuria is more often nonselective
Poor response to corticosteroid therapy
Progression to chronic glomerulosclerosis w/ 50% developing
end-stage renal disease w/in 10 years.
Immunofluorescence microscopy may show nonspecific
deposition (trapping) of IgM and C3 in sclerotic segment.
On microscopy segmental lesions can be seen (but are sometimes missed
due to the biopsy containing insufficient amount of glomeruli). A collapse of
basement membrane, increase in matrix and segmental insudation of
plasma proteins along the capillary wall (hyalinosis) will be seen. Foam cells
are often present. Even in glomeruli that do not exhibit segmental lesions
there may be mesangial matrix and mesangial proliferation.

6. Describe the methods used to quantitate urine excretion

The 24 hour urine collection is a common method. It is reliable but its
disadvantage is the time and dedication it takes to do the proper
collection. Theres also a dipstick and spot check commonly used. The
best method is probably the eGFR because it can diagnose various levels
of kidney disfunction. The downside is that it can be unreliable for certain
people, like the very old or very young, or people that have extensive kidney
disease.
7. Describe the clinical course of common types of nephrotic
syndromes.

It is characterized by proteinuria (>3.5g/day), hypoalbuminemia,

hyperlipidemia and edema. A few other characteristics are:
Puffiness around the eyes, characteristically in the morning.
Edema over the legs which is pitting (i.e., leaves a little pit when the fluid is
pressed out, which resolves over a few seconds).
Fluid in the pleural cavity causing pleural effusion. More commonly
associated with excess fluid is pulmonary edema.
Fluid in the peritoneal cavity causing ascites.
Hypertension (rarely)
Some patients may notice foamy urine, due to a lowering of the surface
tension by the severe proteinuria. Actual urinary complaints such as
hematuria or oliguria are uncommon, and are seen commonly in nephritic
syndrome.
May have features of the underlying cause, such as the rash associated with
Systemic Lupus Erythematosus, or the neuropathy associated with
diabetes.
Examination should also exclude other causes of gross edemaespecially
the cardiovascular and hepatic system.
Minimal change disease: Prednisone is prescribed along with a blood
pressure medication, typically an ACE inhibitor such as lisinopril. Some
nephrologists will start out with the ACE inhibitor first in an attempt to
reduce the blood pressure's force which pushes the protein through
the cell wall in order to lower the proteinuria. In some cases a
corticosteroid may not be necessary if the case of minimal change disease is
mild enough to be treated just with the ACE Inhibitor. Often the liver is
overactive with minimal change disease in an attempt to replace
lost protein and over produces cholesterol. Therefore a statin drug is
often prescribed for the duration of the treatment. When the urine is clear
of protein, the drugs can be discontinued. 50% of patients will
relapse and need further treatment.
Minimal change disease usually responds well to initial treatment, with the
symptoms of nephrotic syndrome (NS) typically going away, but this can take
weeks to months. Younger children, who are more likely to develop
minimal change disease, usually respond faster than adults. In 2 out of 3
children with MCD, however, the symptoms of NS can reoccur, called a
relapse, particularly after an infection or an allergic reaction. This is
typical, and usually requires additional treatment. Many children experience
3 to 4 relapses before the disease starts to go away. Some children require
longer term therapy to keep MCD under control. It appears that the more
time one goes without a relapse, the better the chances are that a relapse
will not occur. In most children with minimal change disease, particularly
among those who respond typically, there is minimal to no permanent
damage observed in their kidneys.

With steroid treatment, the symptoms of nephrotic syndrome (NS) will

go away, called remission, in the majority of children with minimal change
disease. This typically occurs faster, over 2 to 8 weeks, in younger
children, but can take up to 3 or 4 months in adults. Typically the dose
of steroids will initially be fairly high, lasting 1or 2 months. At some
point after the urine protein levels have become normal again, the dose of
steroids might be switched to an every-other-day schedule, then very
slowly reduced over the course of several months. It is very important
to taper, or gradually reduce, the dose of steroids. The body does not
respond well to a sudden discontinuation of steroids, and this might also
trigger a relapse, or return, of NS symptoms. Giving steroids initially for a
longer period of time is thought to reduce the likelihood of relapse. The
majority of children with minimal change disease will respond to this
treatment.
Focal segmental glomerulosclerosis (FSGS) is a cause of nephrotic
syndrome in children and adolescents, as well as an important cause of
kidney failure in adults.[1]
It is also known as "focal glomerular sclerosis" or "focal nodular
glomerulosclerosis".[2]
Treatment is not effective as for minimal change disease. Prognosis is not
very good. Approximately, 50% of adults will progress to kidney failure within
10 years. These are some proposed treatments but patients and doctors
must consider the benefits and disadvantages of treatment.
Salt restriction and diuretics (water pills), such as furosemide, for edema
Antihypertensives (especially ACEIs) if the blood pressure is too high
treat present hyperlipidemia (e.g. statins, fibrates)
Aldosterone antagonist to decrease proteinuria and thus offer a degree of
reno-protection
Corticosteroids, such as prednisone based on the clinical judgment of
physician (no broad consensus/guideline)[citation needed]
Cytotoxics, such as cyclophosphamide may be used to induce remission in
patients presenting with FSGS refractory to corticosteroids, or in patients
who do not tolerate steroids.
Plasmapheresis blood cleansing using a machine to remove the patient's
blood plasma and replacing it with donor plasma.
None sometimes none of the above works and the patient will require
dialysis with possibly later transplantation of a new kidney.[citation needed]
Membranous glomerulonephritis (MGN) is a slowly progressive disease of the
kidney affecting mostly patients between ages of 30 and 50 years, usually
Caucasian.
Some patients may present as nephrotic syndrome with proteinuria, edema
with or without renal failure. Others may be asymptomatic and may be
picked up on screening or urinalysis as having proteinuria. A definitive
diagnosis of membranous nephropathy requires a kidney biopsy.

Treatment of secondary membranous nephropathy is guided by the

treatment of the original disease. For treatment of idiopathic membranous
nephropathy, the treatment options include immunosuppressive drugs and
non-specific anti-proteinuric measures.
[edit]Immunosuppressive therapy
Corticosteroids: They have been tried with mixed results.
Perhaps the most difficult aspect of membranous glomerulonpehritis is
deciding which patients to treat with immunosuppressive therapy as opposed
to simple "background" or anti-proteinuric therapies. A large part of this
difficulty is due to a lack of ability to predict which patient will progress to
end-stage renal disease, or renal disease severe enough to require dialysis.
Because the above medications carry risk, treatment should not be initiated
without careful consideration as to risk/benefit profile. Of note,
corticosteroids (typically Prednisone) alone are of little benefit. They should
be combined with one of the other 5 medications, each of which, along with
prednisone, has shown some benefit in slowing down progression of
membranous nephropathy. It must be kept in mind, however, that each of
the 5 medications also carry their own risks, on top of prednisone.
It is unresolved whether FSGS is a distinct disease or simply an evolution of
minimal change disease.
And membranous for adults
8. List complications of Nephrotic syndrome.
COMPLICATIONS Proteinuria and edema are the principal clinical
manifestations of the nephrotic syndrome. Interstitial fluid tends to
accumulate in dependent areas where tissue turgor is low. Thus periorbital
edema upon awakening in the morning and pedal edema are common.
Edema is often accompanied by serous effusions when it becomes
generalized and massive (anasarca).
Less well appreciated manifestations of the nephrotic syndrome include
protein malnutrition, hypovolemia, acute renal failure, urinary loss of
hormones, hyperlipidemia and the potential for accelerated atherosclerosis,
a tendency to venous thrombosis, and increased susceptibility to infection
[19].
Protein malnutrition A loss in lean body mass with negative nitrogen
balance often occurs in patients with marked proteinuria, although it may be
masked by concurrently increasing edema. This may be compounded by
gastrointestinal symptoms of anorexia and vomiting which are secondary to
edema of the gastrointestinal tract.
Hypovolemia Symptomatic hypovolemia can occur in nephrotic patients,
often as a result of over diuresis in those with a serum albumin less than 1.5
g/dL. Occasional untreated children show signs of volume depletion thought
to be due to severe hypoalbuminemia causing fluid movement into the

interstitium.
Acute renal failure Acute renal failure can develop in some patients with
the nephrotic syndrome, particularly minimal change disease. The
mechanism is not understood; several factors including hypovolemia,
interstitial edema, ischemic tubular injury, and the use of NSAIDs have been
suggested. (See "Acute kidney injury (acute renal failure) in minimal change
disease and other forms of nephrotic syndrome"). Two other major settings
are collapsing FGS, focal glomerulosclerosis, in which the tubular injury is
thought to play an important role, and crescentic glomerulonephritis
superimposed upon membranous nephropathy, in which the urine sediment
becomes active. (See "Causes and diagnosis of membranous nephropathy").
Thromboembolism Patients with the nephrotic syndrome have an
increased incidence (10 to 40 percent of patients) of arterial and venous
thromboemboli, particularly deep vein and renal vein thrombosis [20,21].
Cerebral vein thrombosis has also been rarely reported [22]. The mechanism
of the hypercoagulability is not completely understood. (See "Renal vein
thrombosis and hypercoagulable state in nephrotic syndrome").
Renal vein thrombosis is found disproportionately in patients with
membranous nephropathy, particularly those excreting more than 10 g of
protein per day. It can present acutely or, much more commonly, in an
indolent manner. The acute presentation includes flank pain, gross
hematuria, and a decline in renal function. Most patients are asymptomatic,
and the diagnosis of renal vein thrombosis is suspected only when
pulmonary thromboembolism develops.
Infection Patients with the nephrotic syndrome are susceptible to
infection, which was the leading cause of death in children with the nephrotic
syndrome before antibiotics became available. Pneumococcal infections,
especially peritonitis, were particularly common. The mechanism of the
impairment of normal defense mechanisms is not well understood; low levels
of immunoglobulin G may play a role.
Miscellaneous Proximal tubular dysfunction has been noted in some
patients with the nephrotic syndrome, often in association with advanced
disease. This can result in glucosuria, aminoaciduria, phosphaturia, renal
tubular acidosis, and vitamin D deficiency. A decrease in thyroxine-binding
globulins can cause marked changes in various thyroid function tests,
although patients are clinically euthyroid. (See "Endocrine dysfunction in the
nephrotic syndrome"). Anemia, perhaps due to the urinary loss or impaired
synthesis of erythropoietin, has also been described in a few patients [2325].
9. List Indications for renal biopsy or nephrology referral

 A renal biopsy is a procedure in which a sample of kidney (also called

renal) tissue is obtained. Microscopic examination of the tissue can provide
information needed to diagnose, monitor or treat a renal disorder.
REASONS FOR BIOPSY
Renal biopsy is recommended for selected patients with kidney disease. It
is most commonly performed when less invasive measures are insufficient.
The following are examples of the most common reasons for biopsy:
Hematuria with renal disease Hematuria (blood in the urine) can occur
with a number of conditions that affect the kidneys and urinary tract. While
renal biopsy is not indicated in all cases of hematuria, it may be performed in
those with hematuria as well as progressive renal disease (such as increasing
proteinuria or blood pressure).

Proteinuria Proteinuria (protein in the urine) occurs in many patients with

renal conditions. Renal biopsy is usually reserved for patients with relatively
high or increasing levels of proteinuria or for patients who have proteinuria
along with other signs of renal dysfunction.
A patient with nephrotic syndrome (significant proteinuria, low blood albumin
level, and edema (swelling) of the arms and legs) may need a renal biopsy,
especially if the patient has systemic lupus erythematosus (SLE). Other
patients with nephrotic syndrome may require a renal biopsy, depending
upon the suspected cause of the nephrotic syndrome.
Acute renal failure Renal failure refers to kidney injury that impairs
kidney function. It can occur abruptly (called acute renal failure) or progress
over a period of time (called chronic renal failure). The cause of acute renal
failure can usually be determined without renal biopsy. Biopsy is performed
in those instances when the cause is uncertain.
Acute nephritic syndrome Patients with acute nephritic syndrome have
hematuria, proteinuria, high blood pressure, and impaired renal function.
Renal biopsy may be recommended to determine the cause of nephritic
syndrome unless it can be determined through blood testing.
Indications for nephrology referral
-eGFR <30mL/min/1.73m2
-Unexplained decline in kidney function (>15% in eGFR over 3 months)
-Proteinuria >1g/24hrs (urine protein:creatinine ratio of 100 mg/mmol ~ daily
protein excretion of 1g/24hrs)
-Glomerular haematuria (particularly if proteinuria present)
-CKD, chronic kidney disease (any stage) and hypertension that is hard get to
target

-Diabetes with eGFR <60mL/min/1.73m2

-Unexplained (Hb <100g/L) anaemia with eGFR <60mL/min/1.73m2
10. What is the treatment of nephrotic syndrome?
General measures (supportive):
Monitoring and maintaining euvolemia (the correct amount of fluid in
the body):
monitoring urine output, BP regularly
diuretics (IV furosemide)
Monitoring kidney function:
calculating GFR
Prevent and treat any complications [see below]
Albumin infusions are generally not used because their effect lasts only
transiently.
Prophylactic anticoagulation may be appropriate in some circumstances.
Specific treatment of underlying cause:
Immunosuppression for the glomerulonephritides (corticosteroids,
ciclosporin).
Standard regime for first episode: prednisolone -60 mg/m2/day in 3
divided doses for 4 weeks followed by 40 mg/m2/day in a single dose
on every alternate day for 4 weeks.
Relapses by prednisolone 2 mg/kg/day till urine becomes negative for
protein. Then, 1.5 mg/kg/day for 4 weeks.
Frequent relapses treated by: cyclophosphamide or nitrogen
mustard or ciclosporin or levamisole.
Achieving stricter blood glucose control if diabetic.
Blood pressure control. ACE inhibitors are the drug of choice.
Independent of their blood pressure lowering effect, they have been
shown to decrease protein loss.
Dietary recommendations: Reduce sodium intake to 1000-2000 milligrams
daily. Foods high in sodium include salt used in cooking and at the table,
seasoning blends (garlic salt, Adobo, season salt, etc.) canned soups, canned
vegetables containing salt, luncheon meats including turkey, ham, bologna,
and salami, prepared foods, fast foods, soy sauce, ketchup, and salad
dressings. On food labels, compare milligrams of sodium to calories per
serving. Sodium should be less than or equal to calories per serving.
Eat a moderate amount of high protein animal food: 3-5 oz per meal
(preferably lean cuts of meat, fish, and poultry). Avoid saturated fats such as

butter, cheese, fried foods, fatty cuts of red meat, egg yolks, and poultry
skin. Increase unsaturated fat intake, including olive oil, canola oil, peanut
butter, avocadoes, fish and nuts. Eat low-fat desserts. Increase intake of
fruits and vegetables. There is no potassium or phosphorus restriction
necessary.
Monitor fluid intake, which includes all fluids and foods that are liquid at
room temperature. Fluid management in nephrotic syndrome is tenuous,
especially during an acute flare.