Download MBBS Nephrotic Syndrome Lecture PPT

DEFINITION

? According to ISKDC (International Study of

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Kidney Disease in Children) it is defined as

1. Massive proteinuria - 40 mg/m2/hr (50 mg /

kg / d or 3.5 gm/day)

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2. Hypoalbuminemia ( < 2.5g/dl)
3. Hypercholesterolemia ( >220 mg/dL)
With or without
4. Edema

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Nephrotic syndrome is a clinical complex

characterized by a number of renal and extra renal

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features, most prominent of which are

? Proteinuria (in practice > 3.0 to 3.5gm/24hrs),
? Hypoalbuminemia,
? Edema,

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? Hypertension
? Hyperlipidemia,
? Lipiduria and
? Hypercoagulabilty.

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Classification

Nephrotic syndrome can be

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?Primary, being a disease specific to the

kidneys,

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?Secondary, being a renal manifestation of a

systemic general illness
Primary causes

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Primary causes include-
? Minimal-change nephropathy (70-90% children

and 10- 15% in adult)

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?Focal segmental glomerulosclerosis (FSGS)(15%

in adult)

? Membranous nephropathy (30% in adult)

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?Mesangial proliferative glomerulonephritis .
? Rapidly progressive glomerulonephritis
Secondary causes

Secondary causes include-

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?Diabetes mellitus
? Lupus erythematosus
? Amyloidosis and paraproteinemias
? Viral infections (eg, hepatitis B, hepatitis C,

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HIV )

? Preeclampsia

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?Nephrotic syndrome is 15 times more common

in children

? Most cases in children are due to minimal-

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change disease.

? In adults, the most common form is

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membranous glomerulonephritis, followed by
FSGS.

? Diabetic nephropathy is emerging as a major

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cause of nephrotic syndrome

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? In a healthy individual, less

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than 0.1% of pl. albumin may
traverse the glomerular filtration

barrier.

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?Glomerular capillaries are lined

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by a fenestrated endothelium
that sits on the glomerular
basement membrane

?Which in turn is covered by

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glomerular

epithelium,

or

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podocytes, which envelops the
capillaries

with

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cellular

extensions called foot processes.

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?In between the foot processes are the filtration slits.
?These 3 structures are the glomerular filtration barrier

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- Idiopathic, Drugs, Malignancy, especially

Hodgkin's lymphoma,

- Hepatitis C, autoimmune disease (SLE), and

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diseases of intraglomerular coagulation


Pathophysiology of NS

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Pathophysiology of proteinuria

? The glomerular structural changes that may cause

proteinuria are damage to the endothelial surface, the

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glomerular basement membrane, or the podocytes.

? Glomerular

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haemodynamics

(Intraglomerular

hypertension

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and

hyperfiltration)

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can

alter

Glomerular permeabiality.

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? Selectivity of proteinuria- Excretion of relatively

low M.W. protein (Albumin or transferrin) is known

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as selective proteinuria while if excretion is

predominately high M.W. protein (IgG, IgM or 2

macroglobulin) it is nonselective proteinuria

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? It is



also related to relative damage of Glomerular filter.

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? If there is predominantly loss of charge selectivity

selective proteinuria.

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? If there is predominantly loss of size selectivity

nonselective proteinuria

? A clearance of IgG > 20% of transferrin or albumin

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represents nonselective proteinuria and < 10% is

selective proteinuria.

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? Proteinuira leaking through damaged glomeruli are

toxic to renal tubules.

? So every attempts should be made to prevent and

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reduce proteinuria irrespective of serum protein level or

basic disease
Hypoalbunemia

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? It is due to both the proteinuria and due to the

increase renal catabolism (in tubules).

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? In fact hepatic albumin synthesis is increased from

145?9mg/kg/day to 213?17mg/kg/day in nephrotic
patients.

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Pathogenesis of edema

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Metabolic consequences of proteinuria

? Metabolic consequences of the nephrotic

syndrome include the following:

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Infection
Hyperlipidemia and atherosclerosis
Hypocalcemia and bone abnormalities
Hypercoagulability

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Hypovolemia
Infection in Nephrotic Syndrome

Proposed explanations include the following:
?Urinary immunoglobulin losses

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?Edema fluid acting as a culture medium
?Protein deficiency
? Decreased bactericidal activity of the leukocytes
?Immunosuppressive therapy
?Urinary loss of a complement factor (properdin

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factor B) that opsonizes certain bacteria
Hyperlipedemia

? Due to increase hepatic lipoprotein synthesis that is

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triggered by reduced oncotic pressure.

? Defective lipid catabolism has also important role.
? LDL and cholesterol are increased in majority of

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patients whereas VLDL and triglyceride tends to rise
in patients with severe disease.

? It increases the relative risk for MI 5.5 fold and

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coronary death 2.8 fold.

? It also increases progression of renal disease
Hypercoagulability

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v Multifactorial in origin
v Increase urinary loss of antithrombin III.
v Altered levels and/or activity of protein C & S.
v Hyperfibronogenemia due to increase hepatic

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synthesis.

v Impaired fibrinolysis due to decrease plasminogen.
v Increase platelet aggregability ? relative immobility

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- haemoconcentragtion from hypovolemia. ?
hyperlipidemia

v Alteration in endothelial function

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Hypocalcemia

? Hypocalcemia is common in the nephrotic syndrome,

but rather than being a true hypocalcemia, it is usually

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caused by a low serum albumin level.

? Nonetheless, low bone density and abnormal bone

histology are reported in association with nephrotic

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syndrome.

? This could be caused by urinary losses of vitamin D?

binding proteins, with consequent hypovitaminosis D

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and, as a result, reduced intestinal calcium absorption
Hypovolemia

? Hypovolemia occurs when hypoalbuminemia

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decreases the plasma oncotic pressure

? Resulting in a loss of plasma water into the

interstitium and causing a decrease in circulating

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blood volume.

? Hypovolemia is generally observed only when the

patient's serum albumin level is less than 1.5 g/dL.

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? Hypotension is a late feature
FUNCTIONAL CONSEQUENCE OF URINARY

LOSS OF PLASMA PROTEIN

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? Thyroid binding globulins and thyroxin ? may lead to

hypothyroidism.

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? Vit D binding protein ? osteomalacia, but rare
? Total calcium is also low due to low albumin level.

? Transferrin and erythropoietin and ? microcytic

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hypochromic anaemia.

? ARF ? is rare in nephrotic syndrome. In whom it occur

patient are elderly of minimal changes disease / FGSS

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Clinical Features

COMMON:
? Anorexia, irritability, abdominal pain, diarrhoea and genital

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edema

? Frothy urine (high concentrations of protein)
? Edema may cause dyspnea (pleural effusion or laryngeal

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edema),

? Chest discomfort (pericardial effusion), arthralgia

(hydrarthrosis), or abdominal pain (ascites or, in children,

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mesenteric edema).

? Edema may obscure signs of muscle wasting and cause

parallel white lines in fingernail beds (Muehrcke's lines).

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UNCOMMON:
? Hypertension, Gross hematuria

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? Prolonged NS may result in

nutritional

deficiencies,

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including

protein

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malnutrition

? Myopathy
? Decreased total Ca+2, tetany
? Spontaneous peritonitis and

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opportunistic infections

? Coagulation disorders, with

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decreased

fibrinolytic

activity

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Differential Diagnosis

? Heart failure

? Cirrhosis

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? Glomerulonephritis

? Protein losing enteropathy

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? PEM


INVESTIGATIONS
Urine Analysis

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? Routine exam. : 3+ or 4 +

proteinuria

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? 24 hour urine protein >3.0 gm or

40 mg/m2/hr

? Spot Urine protein/creatinine

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ratio : > 2.0

? Urine protein selectivity
? Hyaline casts

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? Microscopic hematuria in 20%


Proteinuria - Parameters

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Hyaline Cast in urine


Blood

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? S.Cholesterol ( > 250 mg/dL)
? S.Albumin (< 2.5 gm/dl)
? S. A/G ratio ? reversal
? S.Creatinine

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? Bl. Urea
? S . C3 and C4 levels
? CBC : Increased Hb, Platelets, Hct
BLOOD

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? Serum proteins -Total proteins decreased
? Serologic studies for infection and immune

abnormalities

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OTHER INVESTIGATIONS:
? Renal ultrasonography
? Renal biopsy
? CXR: ? Pleural effusion
? Pulm edema - rare

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MANAGEMENT

Specific treatment
? In minimal-change nephropathy, glucocorticosteroids, such

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as prednisone, are used. Children who relapse may be treated

with rituximab

? In some lupus nephritis, prednisone and cyclophosphamide

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are useful

? Secondary amyloidosis with nephrotic syndrome may

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respond to antiinflammatory treatment of the primary disease.

? In membranous nephropathy, expectant management without

immunosuppression can be used for the first 6 months, in

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patients at low risk for progression (ie, those with serum

creatinine level < 1.5 mg/dL).

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? Patients with renal insufficiency (serum creatinine level > 1.5

mg/dL) are at greatest risk for the development of end-stage

renal disease and should receive immunosuppressive therapy.

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[3
DIET AND ACTIVITY

? The diet in patients with nephrotic syndrome

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should provide adequate energy (caloric) intake
and adequate protein (1-2 g/kg/d).

? A diet with no added salt will help to limit fluid

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overload.

? Management of hyperlipidemia could be of some

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importance if the nephrotic state is prolonged.

? Fluid restriction per se is not required.
? Ongoing activity, rather than bed rest, will reduce

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the risk of blood clots
Acute Nephrotic Syndrome in Adults

? Diuretics will be needed; furosemide, spironolactone, and

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even metolazone may be used. Volume depletion may
occur with diuretic use, which should be monitored.

? Anticoagulation has been advocated by some for use in

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preventing thromboembolic complications,

? Hypolipidemic agents may be used, but if the nephrotic

syndrome cannot be controlled, the patient will have

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persistent hyperlipidemia.

? ACE inhibitors and/or ARB are widely used. These may

reduce proteinuria by reducing the systemic blood

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pressure, by reducing intraglomerular pressure, and also by
direct action on podocytes
Management

? Long-Term Monitoring- Follow-up care in

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patients with nephrotic syndrome includes

? Immunization
? Treatment of relapses of steroid-responsive

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nephrotic syndromes,

? Monitoring for steroid toxicity, and
? Monitoring of diuretic and angiotensin

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antagonist regimens.


DIABETIC NEPHROPATHY

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? The earliest morphologic

abnormalities

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in

nephropathy are thickening

of the GBM and expansion

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of mesangium.

? Composition of GBM is

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altered with loss of heparan

sulfate moities.

? Prominent nodular matrix

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expansion

(classical

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Kimmelsteil-Wilson lesion)

are often found.

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