Nephrotic Syndrome

Nephrotic syndrome: A clinical complex characterized by a number of renal and extrarenal features.
• The most prominent features are
Proteinuria of >3.5g per 24 hours (in practice, >3.0 to 3.5 g per 24 h)
hypoalbuminemia
Edema
Hyperlipidemia
Lipiduria
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.
• Mainly is due to either primary and or secondary causes.
Primary Causes
• Disease specific to the kidneys
• Primary causes of Nephrotic syndrome include in approximate order of frequency
Minimal-change nephropathy
Focal glomerulosclerosis
Membranous nephropathy
Hereditary nephropathies
Secondary Causes
• Being a renal manifestation of a systemic general illness
• Secondary causes include again in order of approximate frequency
Diabetes mellitus (DM)
Systemic lupus erythematosus (SLE)
Amyloidosis and paraproteinemias
Viral infections (e.g. hepatitis B, hepatitis C, HIV)
Pre-eclampsia
Other Causes
• Medication can cause nephrotic syndrome.
• This includes the very infrequent occurrence of minimal-change nephropathy with
NSAID use 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
Activity: Small Group Discussion
Instructions
In small groups, discuss to describe the clinical features of nephrotic syndrome. One person
in your group will present the responses after 10 minutes.
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 Diagnosis, Management, Complications and Prognosis of
Nephrotic Syndrome
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.
Investigations and Treatment of Nephrotic Syndrome
Treatment
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
The principles for acute management of adults with nephrotic syndrome are similar to
those for children.
Diuretics will be needed such as Furosemide, Spironolactone and even Metolazone
may be used.
Volume depletion may occur with diuretic use which should be monitored by
assessment of symptoms, weight, pulse and blood pressure.
Anticoagulation has been advocated by some for use in preventing thromboembolic
complications but its use in primary prevention is of unproven value.
Hypolipidemic agents may be used but if the nephrotic syndrome cannot be controlled
there will be persistent hyperlipidemia.
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.
• Provide pre-referral treatment
• Refer the patient to the higher centre for further investigation and management
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.
                                                                                                                       
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