Nephrotic syndrome

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Nephrotic syndrome
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Figure 1. Nephrotic edema.
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Figure 2. Nephrotic edema.
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Clinical Syndrome

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The most common syndrome of kidney disease
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• Nephrotic syndrome
• Nephritic syndrome
• Asymptomatic urinary abnormalities
• Acute renal failure or Rapidly progressive renal
  failure
• Chronic kidney disease(Table 1)

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Table 1. STAGES OF CHRONIC KIDNEY DISEASE
STAGE DESCRIPTION GFR (mL/min/1.73m2)
1 Kidney damage with normal or ? GFR 90
2 Kidney damage with mild or ? GFR 60-89
3 Moderate ? GFR 30-59
4 Severe ? GFR 15-29
5 Kidney failure lt15 (or dialysis)
Chronic kidney disease is defined as either
kidney damage or GFR lt 60mL/min/1.73m2 for
3months. Kidney damage is defined as pathologic
abnormalities or markers of damage, including
abnormalities in blood or urine tests or image
studies.
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Nephrotic syndrome

• This is characterized by proteinuria
  (Typically gt 3.5g/24h),
• hypoalbuminemia ( less than 30g/dL ) and
  edema.
• Hyperlipidaemia is also present.
• Primary and secondary causes are summarized in
  Table 2, 3
• In practice, many clinicians refer to
  nephrotic range proteinuria regardless of
  whether their patients have the other
  manifestations of the full syndrome because the
  latter are consequences of the proteinuria.

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NEPHROTIC SYNDROME

• Pathophysiology
• Proteinuria
• Hypoalbuminemia
• Edema
• Hyperlipidemia
• Cause (diagnosis and differential diagnosis)
• Systemic renal disease
• hepatitis B associated glomerulonephritis,
  Henoch-Schonlein purpura, systemic lupus
  erythematosus, diatetes mellitus, amyloidosis
• Idiopathic nephrotic syndrome
• Complications
• Infection
• Coagulation disorders
• Protein malnutrition and dyslipidemia
• Acute renal failure

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Pathophysiology
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Proteinuria

• Proteinuria can be caused by systemic
  overproduction, tubular dysfunction, or
  glomerular dysfunction. It is important to
  identify patients in whom the proteinuria is a
  manifestation of substantial glomerular disease
  as opposed to those patients who have benign
  transient or postural (orthostatic) proteinuria.

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Heavy proteinuria (albuminuria)
Figure 3.
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Hypoalbuminemia

• Hypoalbuminemia is in part a consequences of
  urinary protein loss. It is also due to the
  catabolism of filtered albumin by the proximal
  tubule as well as to redistribution of albumin
  within the body. This in part accounts for the
  inexact relationship between urinary protein
  loss, the level of the serum albumin, and other
  secondary consequences of heavy albuminuria .

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Edema

• The salt and volume retention in the NS may
  occur through at least two different major
  mechanisms.
• In the classic theory, proteinuria leads to
  hypoalbuminemia, a low plasma oncotic pressure,
  and intravascular volume depletion. Subequent
  underperfusion of the kidney stimulates the
  priming of sodium-retentive hormonal systems such
  as the RAS axis, causing increased renal sodium
  and volume retention, In the peripheral
  capillaries with normal hydrostatic pressures and
  decreased oncotic pressure, the Starling forces
  lead to transcapillary fluid leakage and edema .

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Edema

• In some patients, however, the intravascular
  volume has been measured and found to be
  increased along with suppression of the RAS axis.
  An animal model of unilateral proteinuria shows
  evidence of primary renal sodium retention at a
  distal nephron site, perhaps due to altered
  responsiveness to hormones such as atrial
  natriuretic factor. Here only the proteinuric
  kidney retains sodium and volume and at a time
  when the animal is not yet hypoalbuminemic. Thus,
  local factors within the kidney may account for
  the volume retention of the nephrotic patient as
  well.

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Figure 4.
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Hyperlipidemia

• Most nephrotic patients have elevated levels of
  total and low-density lipoprotein (LDL)
  cholesterol with low or normal high-density
  lipoprotein (HDL) cholesterol . Lipoprotein (a)
  Lp(a) levels are elevated as well and return to
  normal with remission of the nephrotic syndrome.
  Nephrotic patients often have a hypercoagulable
  state and are predisposed to deep vein
  thrombophlebitis, pulmonary emboli, and renal
  vein thrombosis.

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Cause
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Table 2 CAUSES OF THE NEPHROTIC SYNDROME
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Table 3a NEPHROTIC SYNDROME ASSOCIATED
WITH SPECIFIC CAUSES (SECONDARY NEPHROTIC
SYNDROME)
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Table 3b NEPHROTIC SYNDROME ASSOCIATED
WITH SPECIFIC CAUSES (SECONDARY NEPHROTIC
SYNDROME)
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Pathology patterns and
clinical presentations of idiopathic
nephrotic syndome
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Renal biopsy

• In adults, the nephrotic syndrome is a common
  condition leading to renal biopsy. In many
  studies, patients with heavy proteinuria and the
  nephrotic syndromes have been a group highly
  likely to benefit from renal biopsy in terms of a
  change in specific diagnosis, prognosis, and
  therapy.
• Selected adult nephrotic patients such as the
  elderly have a slightly different spectrum of
  disease, but again the renal biopsy is the best
  guide to treatment and prognosis (Table 2, 3).

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PRIMARY NEPHROTIC SYNDROME

• Minimal Change Disease
• Focal Segmental Glomerulosclerosis
• Membranous Nephropathy
• Membranoproliferative Glomerulonephritis (MPGN)

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Figure 5a. Pathology of glomerular disease.
Light microscopy. (a) Normal glomerulus minimal
change disease.
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Table 4
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PRIMARY NEPHROTIC SYNDROME

• Minimal Change Disease
• Focal Segmental Glomerulosclerosis
• Membranous Nephropathy
• Membranoproliferative Glomerulonephritis(MPGN)

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Figure 5b. Segmental sclerosis focal
segmental glomerulosclerosis.
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Figure 6. Light microscopic appearances in
focal segmental glomerulosclerosis. Segmental
scars with capsular adhesions in otherwise normal
glomeruli.
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Table 5
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PRIMARY NEPHROTIC SYNDROME

• Minimal Change Disease
• Focal Segmental Glomerulosclerosis
• Membranous Nephropathy
• Membranoproliferative Glomerulonephritis(MPGN)

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Figure 7a. Early MN a glomerulus from a
patient with severe nephrotic syndrome and early
MN, exhibiting normal architecture and peripheral
capillary basement membranes of normal thickness
(Silvermethenamine 400).
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Figure 7b morphologically advanced MN
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Figure 7c. Morphologically more advanced MN
(same patient as in (b))
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Table 6
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PRIMARY NEPHROTIC SYNDROME

• Minimal Change Disease
• Focal Segmental Glomerulosclerosis
• Membranous Nephropathy
• Membranoproliferative Glomerulonephritis(MPGN)

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Figure 8. Pathology of membranoproliferative
glomerulonephritis type I. (a) Light microscopy
shows a hypercellular glomerulus with accentuated
lobular architecture and a small cellular
crescent (methenamine silver).
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Table 7
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Diagnosis and Differential diagnosis
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• Initial evaluation of the nephrotic patient
  includes laboratory tests to define whether the
  patient has primary, idiopathic nephrotic
  syndrome or a secondary cause related to a
  systemic disease.

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• Common screening tests include the fasting blood
  sugar and glycosylated hemoglobin tests for
  diabetes, and antinuclear antibody test for
  rheumatoid disease, and the serum complement,
  which screen for many immune complex-mediated
  disease (Table 3), In selected patients,
  cryoglobulins, hepatitis B and C serology,
  anti-neutrophil cytoplasmic antibodies (ANCAS),
  anti GBM antibodies, and other tests may be
  useful. Once secondary causes have been excluded,
  treating the adult nephrotic patient often
  requires a renal biopsy to define the pattern of
  glomerular involvement.

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Complications
Infection Coagulation disorders Protein
malnutrition and dyslipidemia Acute renal failure

• It leads to a multitude of other consequences ,
  such as predisposition to infection and
  hypercoagulability. In general, the diseases
  associated with NS cause chronic kidney
  dysfunction, but rarely they can cause ARF. ARE
  may be seen with minimal change disease, and
  bilateral renal vein thrombosis.

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Treatment ??

• 1. General treatment
• 2. Symptomatic treatment (e.g.diuresis to relieve
  edema, treating dyslipidemias, anticoagulate
  treatment, etc.)
• 3. Immunosupressive treatment

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