Nephrotic Syndrome (NS)

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Nephrotic Syndrome (NS)

• Qiang Yao
• Renal Division, Renji Hospital
• Shanghai 2nd Medical Universigy

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Introduction

• Etiology
• Pathophysiology
• Pathology and clinical feature
• Complications
• Diagnosis and differential diagnosis
• Treatment

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Diagnosis
Pro

• Proteinuria gt3.5g/d
• Hypoalbuminemia SAlb lt30g/L
• Edema
• Hyperlipidemia.

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Hypoproteinemia

• Albumin
• Immunoglobulins
• Metal binding proteins
• Erythropoietin urinary
  loss
• Transferrin
• Complement deficiency
• Coagulation components

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Hyperlipidemia

• Hypercholesterolemia
• Hypertriglyceridemia
• Low-density lipoproteins (LDL)
• Very low- density lipoproteins (VLDL)

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chemical composition of plasma lipoprotein ()

• CM VLDL
  LDL HDL
• protein 2 10
  20 45
• lipide 98 90
  80 55
• triglyceride 88
  55 8 10
• phospholipid 6
  20 24 22
• cholesterol total 4
  15 48 23
• free 1
  5 8
  6
• ester 3
  10 40
  17
• lipide/protein 4050 9 4
  11.5

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Mechanisms of Hyperlipidemia

• Increased hepatic synthesis of LDL, VLDL and
  lipoprotein (a) in response to hypoalbuminemia
• Urinary loss of HDL
• Enzymatic changes with abnormal lipid biosythesis
  and degradation

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Edema

• Lower colloid osmotic pressure?
• 15mmHg
  H2O
• colloid osmotic pressure 26 mmHg

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Edema

• Water and sodium retention?
• Does it related with renin-angiotensin-aldosterone
  system?

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How many pathological types causes nephrotic
syndrome?
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Glomerular diseases that cause NS--
Minimal Change Glomerulopathy

• Epidemiology
• It is most common reason of NS in children,
  accounting for 80-90 of young patients with
  nephrotic syndrome , while only 20-25 in
  adults.
• There appears to be a male preponderance,
  especially in children, in whom the male- to-
  female ratio is 23 1

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Glomerular diseases that cause NS--
Minimal Change Glomerulopathy

• Pathology
• No glomerular lesions by light microscopy
• No staining with antisera specific for
  immunoglobulins or complement components.
• Effacement of visceral epithelial cell foot
  processes

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Glomerular diseases that cause NS--
Minimal Change Glomerulopathy

• Clinical features
• The cardinal clinical feature of minimal change
  glomerulopathy in children is the relatively
  abrupt onset of proteinuria and development of
  the NS.
• Hematuria, hypertension and impaired renal
  function are not common.

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Glomerular diseases that cause NS--
mesangial proliferative GN

• Epidemiology
• It is a common reason of NS in our country,
  accounting for 30 of primary nephrotic syndrome,
  higher than those in western.

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Glomerular diseases that cause NS--
mesangial proliferative GN

• Pathology
• Diffuse proliferation of mesangial cells and ECM
• Positive staining with IgA, IgG, IgM or C3 in
  mesangial area
• Dense deposits in mesangial area

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Glomerular diseases that cause NS--
Mesangial Proliferative GN

• Clinical features
• 50 has infection before onset of renal disease.
• Non-IgAN 50 with NS, 70 with hematuria
• IgAN15 with NS, almost all with hematuria

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Glomerular diseases that cause NS--
Mesangial Capilary Glomerulonephritis

• Epidemiology
• It is accounting for 10 of nephrotic syndrome
  patients in our country .

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Glomerular diseases that cause NS--
Mesangial Capilary Glomerulonephritis

• Pathology
• Severe diffuse proliferation of mesangial cells
  and ECM, demonstrating doubling and more complex
  replication of glomerular basement membranes
• Peripheral granular to bandlike staining for C3
  and IgG
• Dense deposits in mesangial subendothelial area

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Glomerular diseases that cause NS--
Mesangial Capilary Glomerulonephritis

• Clinic feature
• 30 has infection before onset of renal disease
  (nephritic syndrome), half of them present as a
  nephrotic syndrome.
• Almost all of patients with hematuria
• Early onset of impairment of renal function,
  hypertension, anemia
• Progressive procedure (10 year renal survival
  rate was less than 65)

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Glomerular diseases that cause NS--
Membranous Glomerulopathy

• Epidemilology
• Idiopathic membranous glomerulopathy is the most
  common cause for nephrotic syndrome in adults

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Glomerular diseases that cause NS--
Membranous Glomerulopathy

• Pathology
• Subepithelial immune complex projections of
  basement membrane deposits surrounded by
  basement membrane thickened basement membrane
• IgG and C3 positive staining in capillary

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Glomerular diseases that cause NS--
Membranous Glomerulopathy

• Clinic feature
• 80 with NS
• 5-10 years later, renal function declined
• Renal vein thrombosis is not uncommon (4-52)

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Glomerular diseases that cause NS--
Focal Segmental Glomerulosclerosis

• Epidemilology
• Over the past two decades, there has been an
  increased incidence of FSGS, accounting for 10
  in our country.
• Some cases developed from minimal changes GN.

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Glomerular diseases that cause NS-- Focal
Segmental Glomerulosclerosis

• Pathology
• It is characterized by focal and segmental
  glomerular sclerosis
• Nonsclerotic glomeruli and segments usually have
  no staining for immunoglobulins or complement.

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Glomerular diseases that cause NS--
Focal Segmental Glomerulosclerosis

• Clinic feature
• NS
• With hematuria
• Hypertension and renal function declining are
  common

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Diagnosis

• Diagnosis
• NS?
• Primary or secondary?
• Complications?

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Differential diagnosis

• Primary
  Secondary
• children minimal change allergic
  purpura nephritis
• Teenager mesangial proliferative FSGS
• nephritis
• Middle age mesengial capillary SLE LN
• nephritis
• old age membranous myeloma,
  amyloidosis
• nephropathy

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Complications

• Infection
• malnutrition
• loss of immunoglobulins
• corticosteroids
• Thrombosis
• coagulation, coricosteroids, PLT activity

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Complications

• Acute renal failure( ARF)
• Hypoalbuminemia Hypovolemia pre-renal
• 
  azotemia
• Dyslipidemia

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Treatment

• Support care
• Rest in bed limitation of protein
  intake(0.8-1.0g/kg/d) limitation of salt intake
  (lt3g/d)
• Diuretic therapy
• Diminishing proteinuria ACEI and ARB

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Treatment

• Inhibition of inflammation and immune response
• Corticosteroid therapy (onset)
• for children prednisone 60mg/m2/d
• for adult prednisone 1mg/kg/d (lt80mg/d)
• 4-6 weeks later , complete remission of
  proteinturia occurs, the dosage then decreased
  (10 every 1-2 weeks).
• Be careful for the side effects of
  corticosteroid therapy

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Patterns of response of cordicosteroids

• Prognosis

Primary responder, no relapse (steroid sensitive)
Primary responder with only one relapse in the first 6 mo after an initial response
Initial steroid response with two or more relapses within 6 mo (frequent relapse)
Initial steroid-induced remission with relapses during tapering of corticosteroid, or within 2 wk after their withdrawal (steroid dependent)
Steroid-induced remission, but no response to a subsequent relapse
No response to treatment (steroid resistant)
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Treatment

• Cytotoxic drugs with corticosteroid
• (for steroid dependent
  or steroid resistant)
• Cyclophosphamide (CTX) p.o. or intravenously
• Side effects liver injury, inhibition of bone
  marrow, etc.
• Cyclosporine
• (for those failed responsing to combination
  of steroid and cytotoxic drugs)
• Dose 5mg/kg/d, bid, p.o.
• Side effects renal and liver toxic injury,
  expensive, etc.

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Treatment

• Mycophenolate mofetil, MMF
• (for steroid dependent
  or steroid resistant)
• Dose1.5-2g/d, bid, p.o. for 3-6 months,
  maintaining 0.5 year

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Treatment

• Minimal changes sensitive to steroids single
  drug reuse when relapse combined with cytotoxic
  drugs when resistant or dependent on steroids
• Membranous GN combine steroid with cytotoxic
  drugs or cyclosporin avoid using drugs when
  Scrgt354umol/L for the patients with risks for
  progressing, otherwise, investigate 6 months
  (antihypertensive).

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Treatment

• FSGS sensitive to steroids in 30-50 of
  patients slow response to therapy steroids
  therapy (onset) for 3-4 months if not response
  until 6 month (resistant), then try cyclosporine.
• Mesangial proliferative GN no evidence show that
  adults will response to steroids aspirin

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Treatment

• Treatment for complications
• Infection
• Thrombosis
• ARF(HD cordicosteroids, diuresis, SB)
• dyslipidemia