Download MBBS (Bachelor of Medicine and Bachelor of Surgery) Latest Nephrotic Syndrome Lecture PPT
DEFINITION
? According to ISKDC (International Study of
Kidney Disease in Children) it is defined as
1. Massive proteinuria - 40 mg/m2/hr (50 mg /
kg / d or 3.5 gm/day)
2. Hypoalbuminemia ( < 2.5g/dl)
3. Hypercholesterolemia ( >220 mg/dL)
With or without
4. Edema
Nephrotic syndrome is a clinical complex
characterized by a number of renal and extra renal
features, most prominent of which are
? Proteinuria (in practice > 3.0 to 3.5gm/24hrs),
? Hypoalbuminemia,
? Edema,
? Hypertension
? Hyperlipidemia,
? Lipiduria and
? Hypercoagulabilty.
Classification
Nephrotic syndrome can be
?Primary, being a disease specific to the
kidneys,
?Secondary, being a renal manifestation of a
systemic general illness
Primary causes
Primary causes include-
? Minimal-change nephropathy (70-90% children
and 10- 15% in adult)
?Focal segmental glomerulosclerosis (FSGS)(15%
in adult)
? Membranous nephropathy (30% in adult)
?Mesangial proliferative glomerulonephritis .
? Rapidly progressive glomerulonephritis
Secondary causes
Secondary causes include-
?Diabetes mellitus
? Lupus erythematosus
? Amyloidosis and paraproteinemias
? Viral infections (eg, hepatitis B, hepatitis C,
HIV )
? Preeclampsia
?Nephrotic syndrome is 15 times more common
in children
? Most cases in children are due to minimal-
change disease.
? In adults, the most common form is
membranous glomerulonephritis, followed by
FSGS.
? Diabetic nephropathy is emerging as a major
cause of nephrotic syndrome
? In a healthy individual, less
than 0.1% of pl. albumin may
traverse the glomerular filtration
barrier.
?Glomerular capillaries are lined
by a fenestrated endothelium
that sits on the glomerular
basement membrane
?Which in turn is covered by
glomerular
epithelium,
or
podocytes, which envelops the
capillaries
with
cellular
extensions called foot processes.
?In between the foot processes are the filtration slits.
?These 3 structures are the glomerular filtration barrier
- Idiopathic, Drugs, Malignancy, especially
Hodgkin's lymphoma,
- Hepatitis C, autoimmune disease (SLE), and
diseases of intraglomerular coagulation
Pathophysiology of NS
Pathophysiology of proteinuria
? The glomerular structural changes that may cause
proteinuria are damage to the endothelial surface, the
glomerular basement membrane, or the podocytes.
? Glomerular
haemodynamics
(Intraglomerular
hypertension
and
hyperfiltration)
can
alter
Glomerular permeabiality.
? Selectivity of proteinuria- Excretion of relatively
low M.W. protein (Albumin or transferrin) is known
as selective proteinuria while if excretion is
predominately high M.W. protein (IgG, IgM or 2
macroglobulin) it is nonselective proteinuria
? It is
also related to relative damage of Glomerular filter.
? If there is predominantly loss of charge selectivity
selective proteinuria.
? If there is predominantly loss of size selectivity
nonselective proteinuria
? A clearance of IgG > 20% of transferrin or albumin
represents nonselective proteinuria and < 10% is
selective proteinuria.
? Proteinuira leaking through damaged glomeruli are
toxic to renal tubules.
? So every attempts should be made to prevent and
reduce proteinuria irrespective of serum protein level or
basic disease
Hypoalbunemia
? It is due to both the proteinuria and due to the
increase renal catabolism (in tubules).
? In fact hepatic albumin synthesis is increased from
145?9mg/kg/day to 213?17mg/kg/day in nephrotic
patients.
Pathogenesis of edema
Metabolic consequences of proteinuria
? Metabolic consequences of the nephrotic
syndrome include the following:
Infection
Hyperlipidemia and atherosclerosis
Hypocalcemia and bone abnormalities
Hypercoagulability
Hypovolemia
Infection in Nephrotic Syndrome
Proposed explanations include the following:
?Urinary immunoglobulin losses
?Edema fluid acting as a culture medium
?Protein deficiency
? Decreased bactericidal activity of the leukocytes
?Immunosuppressive therapy
?Urinary loss of a complement factor (properdin
factor B) that opsonizes certain bacteria
Hyperlipedemia
? Due to increase hepatic lipoprotein synthesis that is
triggered by reduced oncotic pressure.
? Defective lipid catabolism has also important role.
? LDL and cholesterol are increased in majority of
patients whereas VLDL and triglyceride tends to rise
in patients with severe disease.
? It increases the relative risk for MI 5.5 fold and
coronary death 2.8 fold.
? It also increases progression of renal disease
Hypercoagulability
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
synthesis.
v Impaired fibrinolysis due to decrease plasminogen.
v Increase platelet aggregability ? relative immobility
- haemoconcentragtion from hypovolemia. ?
hyperlipidemia
v Alteration in endothelial function
Hypocalcemia
? 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 losses of vitamin D?
binding proteins, with consequent hypovitaminosis D
and, as a result, reduced intestinal calcium absorption
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.
? Hypotension is a late feature
FUNCTIONAL CONSEQUENCE OF URINARY
LOSS OF PLASMA PROTEIN
? Thyroid binding globulins and thyroxin ? may lead to
hypothyroidism.
? Vit D binding protein ? osteomalacia, but rare
? Total calcium is also low due to low albumin level.
? Transferrin and erythropoietin and ? microcytic
hypochromic anaemia.
? ARF ? is rare in nephrotic syndrome. In whom it occur
patient are elderly of minimal changes disease / FGSS
Clinical Features
COMMON:
? Anorexia, irritability, abdominal pain, diarrhoea and genital
edema
? Frothy urine (high concentrations of protein)
? Edema may cause dyspnea (pleural effusion or laryngeal
edema),
? Chest discomfort (pericardial effusion), arthralgia
(hydrarthrosis), or abdominal pain (ascites or, in children,
mesenteric edema).
? Edema may obscure signs of muscle wasting and cause
parallel white lines in fingernail beds (Muehrcke's lines).
UNCOMMON:
? Hypertension, Gross hematuria
? Prolonged NS may result in
nutritional
deficiencies,
including
protein
malnutrition
? Myopathy
? Decreased total Ca+2, tetany
? Spontaneous peritonitis and
opportunistic infections
? Coagulation disorders, with
decreased
fibrinolytic
activity
Differential Diagnosis
? Heart failure
? Cirrhosis
? Glomerulonephritis
? Protein losing enteropathy
? PEM
INVESTIGATIONS
Urine Analysis
? Routine exam. : 3+ or 4 +
proteinuria
? 24 hour urine protein >3.0 gm or
40 mg/m2/hr
? Spot Urine protein/creatinine
ratio : > 2.0
? Urine protein selectivity
? Hyaline casts
? Microscopic hematuria in 20%
Proteinuria - Parameters
Hyaline Cast in urine
Blood
? S.Cholesterol ( > 250 mg/dL)
? S.Albumin (< 2.5 gm/dl)
? S. A/G ratio ? reversal
? S.Creatinine
? Bl. Urea
? S . C3 and C4 levels
? CBC : Increased Hb, Platelets, Hct
BLOOD
? Serum proteins -Total proteins decreased
? Serologic studies for infection and immune
abnormalities
OTHER INVESTIGATIONS:
? Renal ultrasonography
? Renal biopsy
? CXR: ? Pleural effusion
? Pulm edema - rare
MANAGEMENT
Specific treatment
? In minimal-change nephropathy, glucocorticosteroids, such
as prednisone, are used. Children who relapse may be treated
with rituximab
? In some lupus nephritis, prednisone and cyclophosphamide
are useful
? Secondary amyloidosis with nephrotic syndrome may
respond to antiinflammatory treatment of the primary disease.
? In membranous nephropathy, expectant management without
immunosuppression can be used for the first 6 months, in
patients at low risk for progression (ie, those with serum
creatinine level < 1.5 mg/dL).
? 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.
[3
DIET AND ACTIVITY
? The diet in patients with nephrotic syndrome
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
overload.
? Management of hyperlipidemia could be of some
importance if the nephrotic state is prolonged.
? Fluid restriction per se is not required.
? Ongoing activity, rather than bed rest, will reduce
the risk of blood clots
Acute Nephrotic Syndrome in Adults
? Diuretics will be needed; furosemide, spironolactone, and
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
preventing thromboembolic complications,
? Hypolipidemic agents may be used, but if the nephrotic
syndrome cannot be controlled, the patient will have
persistent hyperlipidemia.
? ACE inhibitors and/or ARB are widely used. These may
reduce proteinuria by reducing the systemic blood
pressure, by reducing intraglomerular pressure, and also by
direct action on podocytes
Management
? Long-Term Monitoring- Follow-up care in
patients with nephrotic syndrome includes
? Immunization
? Treatment of relapses of steroid-responsive
nephrotic syndromes,
? Monitoring for steroid toxicity, and
? Monitoring of diuretic and angiotensin
antagonist regimens.
DIABETIC NEPHROPATHY
? The earliest morphologic
abnormalities
in
nephropathy are thickening
of the GBM and expansion
of mesangium.
? Composition of GBM is
altered with loss of heparan
sulfate moities.
? Prominent nodular matrix
expansion
(classical
Kimmelsteil-Wilson lesion)
are often found.
This post was last modified on 30 November 2021