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Nephrotic Syndrome in Children Lecture Full: Part 1

This is the Lecture of Nephrotic Syndrome taken by our teacher Dr. ShahabuddinMahmud Assistant Professor, Paediatric Nephrology in Rajshahi Medical College. It contains some definitions, cause, Pathophysiology, Structural arrangements, clinical features, treatment options etc. This is mostly suitable for the Medical students to prepare their lessons. I have also included the PDF download link of the Power point presentation. I also believe that this document will help the teachers to arrange the Lectures. If you want to include any information’s here, feel free to write me.

Todays lecture is about Nephrotic Syndrome (NS). NS and Acute Glomerulonephritis (AGN) are closely related.

Proteinuria : Passage of protein in the urine. Normal subject usually excrete about 40-80mg of protein per day ( max. up to 150mg/day).

Composition of U. Protein- (1)Albumin (less than 20mg/day) (2) Tamm-Horsfall mucoprotein (30-50mg/day)

Abnormal Proteinuria: Proteinuria of 4-40mg/m2/hr

Nephrotic range Proteinuria: Proteinuria of >40mg/m2/hr

Definition of Nephrotic Syndrome (NS) · NS is characterized by heavy proteinuria, hypoproteinemia, generalized edema and hyperlipidemia.

Heavy proteinuria- when urinary protein excretion more than 40mg/m2/hour or 1g/m2/24hours.

Hypoproteinemia- serum albumin <2.5g/dl.

Hyperlipidemia-serum cholesterol>250mg/dl.

Nephrotic Syndrome in Children

Incidence of Nephrotic Syndrome (NS)

  • NS is a common disease all over the world
  • Overall incidence is reported to be 2040/million population
  • In USA & in Europe, the incidence is 1013/million children under 16 years of age.
  • In the Indian subcontinent the incidence is estimated as 90-100/million population

The Main 4 Criteria of

Nephrotic syndrome

  1. Massive proteinuria
  2. Hypoalbuminemia
  3. Edema
  4. Hyperlipidemia

Nephritic syndrome:

  1. Hematuria
  2. Oliguria
  3. Azotemia
  4. Hypertension

Glomerular capillary structure:

The glomerular capillary wall consists of three layers ­ fenestrated endothelial layer, a basement membrane and an epithelial layer.

The GBM consists of ­a central electron dense layer, lamina densa and two adjacent layers lamina rara interna & externa.

GBM acts as a semi permeable filter preventing the passage of macromolecules allowing fluids and low molecular weight solutes. The passage of molecules with a diameter of more than 4.5 nm is blocked.

GBM-epithelial layer:

Podocytes of the epithelial cells have an important role in the normal functioning of the glomerular slit membrane.

A number of proteins identified on this podocytes critical for the integrity of glomerular filter, eg, Podocin, Nephrin, Synaptopodin, Alpha-actin 4,P-cadherin.

Gene mutation affecting some of the proteins may result in hereditary nephropathies.

Types and Causes of Nephrotic Syndrome:

Primary 95%. It is idiopathic and most common.

  1. Pure MCD/Minimal Change Nephrotic Syndrome (MCNS) – 76.4%
  2. MCD with mesangial proliferation ­ 2.3%
  3. Focal segmental glomerulosclerosis ­ 6.9%
  4. Membranoproliferative GN ­ 7.5%
  5. Membranous nephropathy ­ 1.5%
  6. Others ­ 5.4%

Secondary 3-5%

  1. Infections: HBV, HCV, Malaria, HIV, Syphilis
  2. Drugs: NSAID, Penicillamine
  3. Systemic disease: SLE
  4. Malignancy: Leukaemia, Lymphoma

Important definitions:

Remission – Protein free urine (<4mg/m2/h) for 3 consecutive days.

Relapse – proteinuria 3+ or more for 3 consecutive days, after having been in remission
Frequent Relapse –A Relapser who has 2 or more relapse within 6 months of the initial episode or more than 3 relapses within any 12 months period.
Infrequent Relapser -a responder who relapses but 3 or less relapses within one year.
Steroid dependent – Occurrence of 2 consecutive relapses during alternate day prednisolone therapy or within 2 wks. of its discontinuation.
Steroid resistant- ­ Failure to achieve remission following 8 week’ Prednisolone 60mg/m2.

Pathogenesis of Minimal Change Nephrotic Syndrome:

Immunologic mechanism may be involved in the pathogenesis of MCNS.
T-cell activation might led to the production of a cytokine that may affect the filtration of proteins by the glomerular capillaries, by interfering with the polyanionic charge or through some other undefined mechanism.

Several study results regarding pathogenesis of MCNS has been shown:

  1. Diminished cellular immunity
  2. Low IgG
  3. Abnormalities of T-lymphocytes cell subsets.
  4. Increase serum level of soluble IL-2 receptor, IL-8,TNF
  5. Vascular permeability factor
  6. Up regulation of the gene for IL-4 and IL-13 in peripheral blood lymphocyte and glomeruli

Pathophysiology of Glomerular Leakage of Protein

The size-selective barrier, which is thought to consist of pores in the glomerular-basementmembrane meshwork, restricts the passage of larger plasma proteins (more than 150 kd).
Investigations have revealed that the defect in minimal-change glomerulopathy results mainly from a loss of charge selectivity, whereas the defect in membranous glomerulonephritis results mainly from a loss of size selectivity.

Hyperlipidemia

HMG co reductase in liver limits the biosynthesis of cholesterol. Hyperlipidemia is related to the severity of proteinuria and hypoalbuminemia.
In NS, hypoalbuminemia causes
Up regulation of HMG co reductase.
Down regulation of lipoprotein lipase, VLDL receptor and hepatic triglyceride lipase.
There is increased production of all lipids and decrease in receptor mediated removal of lipoprotein and lipoprotein lipase.

Treatment: Dietary modification, HMG co reductase inhibitor (atrovastatin, simvastatin etc)

Clinical Feature of Minimal Change Nephrotic Syndrome:

  • Onset of MCNS is between 2-6years.
  • Onset beyond 8 years associated with significant glomerular injury.
  • More in boys 60-70%.
  • Insidious onset, with puffiness, gradual involvement of extremities and abdomen, if untreated may become massive

Clinical evaluation:

  • The child should be examined to detect any associated infection.
  • In MCNS, BP is usually normal. With massive edema it may be elevated. Hypovolemia stimulates several vasoconstricting mechanisms that lead to HTN.
  • Features of systemic disorder should be looked for like- fever, rash, joint pain, hepatosplenomegaly and lymphadenopathy.
  • Associated ARI is common.
  • Mild diarrhoea is not uncommon, probably due to intestinal edema.
  • Occasionally generalized swelling may develop acutely and be associated with gross haematuria.

The Next Part of the Lecture and PDF Download link is coming soon……..

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