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 asystemic 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 commonin 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 byFSGS.
? Diabetic nephropathy is emerging as a major
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cause of nephrotic syndrome--- Content provided by FirstRanker.com ---
? In a healthy individual, less
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than 0.1% of pl. albumin maytraverse the glomerular filtration
barrier.
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?Glomerular capillaries are lined
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by a fenestrated endotheliumthat sits on the glomerular
basement membrane
?Which in turn is covered by
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glomerularepithelium,
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, especiallyHodgkin'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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canalter
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 ispredominately high M.W. protein (IgG, IgM or 2
macroglobulin) it is nonselective proteinuria
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? It isalso 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 selectivitynonselective 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 aretoxic 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 from145?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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HypovolemiaInfection 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 absorptionHypovolemia
? 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 FeaturesCOMMON:
? 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 innutritional
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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decreasedfibrinolytic
activity
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Differential Diagnosis? Heart failure
? Cirrhosis
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? Glomerulonephritis
? Protein losing enteropathy
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? PEMINVESTIGATIONS
Urine Analysis
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? Routine exam. : 3+ or 4 +
proteinuria
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? 24 hour urine protein >3.0 gm or40 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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MANAGEMENTSpecific treatment
? In minimal-change nephropathy, glucocorticosteroids, such
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as prednisone, are used. Children who relapse may be treatedwith 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 > 1.5mg/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 clotsAcute Nephrotic Syndrome in Adults
? Diuretics will be needed; furosemide, spironolactone, and
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even metolazone may be used. Volume depletion mayoccur 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 bydirect 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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innephropathy 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 heparansulfate moities.
? Prominent nodular matrix
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expansion
(classical
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Kimmelsteil-Wilson lesion)are often found.
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