Prepared by:-

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Nephrotic Syndrome..(NS)

• Prepared by-
• Mohammad Ali Al-shehri
• ..
• Supervised by
• Dr.

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Introduction

• Definition of NS
• Etiology of NS
• Pathology of NS
• Pathophysiology of NS
• Clinical Manifestation of NS
• Complication NS
• Laboratory Data
• Diagnosis
• Treatment

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Nephrotic syndrome

• Nephrotic syndrome (NS) results from increased
  permeability of Glomeulrar basement membrane
  (GBM) to plasma protein.
• It is clinical and laboratory syndrome
  characterized by massive proteinuria, which lead
  to hypoproteinemia ( hypo-albuminemia),
  hyperlipidemia and pitting edema.
• (4-increase, 1-decrease).

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Nephrotic Criteria-
Massive proteinuria qualitative
proteinuria 3 or 4, quantitative
proteinuria more than 40 mg/m2/hr in children
(selective). Hypo-proteinemia
total plasma proteins lt 5.5g/dl and serum albumin
lt 2.5g/dl. Hyperlipidemia serum
cholesterol gt 5.7mmol/L Edema pitting
edema in different degree
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Nephritic Criteria

• -Hematuria RBC in urine (gross hematuria)
• -Hypertension
• 130/90 mmHg in school-age children
• 120/80 mmHg in preschool-age children
• 110/70 mmHg in infant and toddlers children
• -Azotemia(renal insufficiency)
• Increased level of serum BUN ?Cr
• -Hypo-complementemia
• Decreased level of serum c3

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Classification

• A-Primary Idiopathic NS (INS) majority
• The cause is still unclear up to now.
  Recent 10 years ,increasing evidence has
  suggested that INS may result from a
  primary disorder of T cell function.
• Accounting for 90 of NS in child. mainly
  discussed.
• B-Secondary NS
• NS resulted from systemic diseases, such as
  anaphylactoid purpura , systemic lupus
  erythematosus, HBV infection.
• C-Congenital NS rare
• 1st 3monthe of life ,only treatment renal
  transplantation

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Secondary NS

• Drug,Toxic,Allegy mercury, snake venom,
  vaccine, pellicillamine, Heroin, gold, NSAID,
  captopril, probenecid, volatile hydrocarbons
• Infection APSGN, HBV, HIV, shunt nephropathy,
  reflux nephropathy, leprosy, syphilis,
  Schistosomiasis, hydatid disease
• Autoimmune or collagen-vascular diseases SLE,
  Hashimotos thyroiditis,, HSP, Vasculitis
• Metabolic disease Diabetes mellitus
• Neoplasma Hodgkins disease, carcinoma ( renal
  cell, lung, neuroblastoma, breast, and etc)
• Genetic Disease Alport syn, Sickle cell
  disease, Amyloidosis, Congenital nephropathy
• Others Chronic transplant rejection, congenital
  nephrosclerosis

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Idiopathic NS (INS) Pathology-

• Minimal Change Nephropathy (MCN) lt80
• The glomeruli appear normal basically Under Light
  microscopy, and Under Immunofluorescence
• under Electron microscopy fusion of the foot
  processes of the podocytes
• (2) NonMCN lt20
• Mesangial proliferative glomerulonephritis
• (MsPGN) about 10
• Focal segmental glomerulosclerosis (FSGS) 5
• Membranous Nephropathy (MN) 2
• Membrane proliferative glomerulonephritis
• (MPGN) 1
• Others rare,Cresent glomerulonephritis

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• NB-
• Nephrotic syndrome is 15 times more common in
  children than in adults.
• Most cases of primary nephrotic syndrome are in
  children and are due to minimal-change disease.
  The age at onset varies with the type of
  nephrotic syndrome.

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Pathophysiology

• The Main Trigger Of primary Nephrotic Syndrome
  and Fundamental and highly important change of
  pathophysiology -
• Proteinuria

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Pathogenesis of Proteinuria-

• Increase glomerular permeability for proteins
  due to loss of negative charged glycoprotein
• Degree of protineuria-
• Mild less than 0.5g/m2/day
• Moderate 0.5 2g/m2/day
• Sever more than 2g/m2/day
• Type of proteinuria-
• A-Selective proteinuria where proteins of low
  molecular weight .such as albumin, are excreted
  more readily than protein of HMW
• B-Non selective
• LMWHMW are lost in urine

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pathogenesis of hypoalbuminemia

• Due to hyperproteinuria----- Loss of plasma
  protein in urine mainly the albumin.
• Increased catabolism of protein during acute
  phase.

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pathogenesis of hyperlipidemia-

• Response to Hypoalbuminemia ? reflex to liver
  --? synthesis of generalize protein (
  including lipoprotein ) and lipid in the liver
  ,the lipoprotein high molecular weight no loss
  in urine ? hyperlipidemia
• Diminished catabolism of lipoprotein

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pathogenesis of edema-

• Reduction plasma colloid osmotic pressure??
  secondary to hypoalbuminemia? Edema and
  hypovolemia
• Intravascular volume?? antidiuretic hormone (ADH
  ) and aldosterone(ALD) ?? water and sodium
  retention? Edema
• Intravascular volume?? glomerular filtration
  rate
• (GFR)?? water and sodium retention ? Edema

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How many pathological types causes nephrotic
syndrome?
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Clinical Manifestation-

• IN MCNS , The male preponderance of 21
• 1.Main manifestations
• Edema (varying degrees) is the common symptom
• Local edema edema in face , around eyes(
  Periorbital swelling) , in lower extremities.
• Generalized edema (anasarca), edema in penis and
  scrotum.
• 2-Non-specific symptoms
• Fatigue and lethargy
• loss of appetite, nausea and vomiting ,abdominal
  pain , diarrhea
• body weight increase, urine output decrease
• pleural effusion (respiratory distress)

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Investigations-

• 1-Urine analysis-
• A-Proteinuria 3-4 SELECTIVE.
• b-24 urine collection for protein
• gt40mg/m2/hr for children
• c- volume oliguria (during stage of edema
  formation)
• d-Microscopically-
• microscopic hematuria 20, large number of
  hyaline cast

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Investigations-

• 2-Blood
• A-serum protein decrease gt5.5gm/dL , Albumin
  levels are low (lt2.5gm/dL).
• B-Serum cholesterol and triglycerides
  Cholesterol gt5.7mmol/L (220mg/dl).
• C-- ESR?gt100mm/hr during activity phase
• .
• 3.Serum complemen Vary with clinical type. 
• 4.Renal function
• .

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Kidney Biopsy-

• Considered in
• 1-Secondary N.S
• 2-Frequent relapsing N.S
• 3-Steroid resistant N.S
• 4- Hematuria
• 5-Hypertension
• 6- Low GFR

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Differential Diagnosis of NS

• D.D of generalized edema-
• 1-Protein losing enteropathy
• 2-Hepatic Failure.
• 3-HF
• 4-Protein energy malnutrition
• 5-Acute and chronic GN
• 6-urticaria? Angio edema

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Complications of NS-

• 1-InfectionsInfections is a major complication
  in children with NS. It frequently trigger
  relapses.
• Nephrotic pt are liable to infection because
• A-loss of immunoglobins in urine.
• B-the edema fluid act as a culture medium.
• C-use immunosuppressive agents.D- malnutrition
• The common infection URI, peritonitis,
  cellulitis and UTI may be seen.
• Organisms encapsulated (Pneumococci,
  H.influenzae), Gram negative (e.g E.coli

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Complication

• Vaccines in NS-
• polyvalent pneumococcal vaccine (if not
  previously immunized) when the child is in
  remission and off daily prednisone therapy.
• Children with a negative varicella titer should
  be given varicella vaccine.

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Complication..

• 2-Hypercoagulability (Thrombosis).
• Hypercoagulability of the blood leading to venous
  or arterial thrombosis
• Hypercoagulability in Nephrotic syndrome caused
  by
• 1-Higher concentration of I,II, V,VII,VIII,X and
  fibrinogen
• 2- Lower level of anticoagulant substance
  antithrombin III
• 3-decrease fibrinolysis.
• 4-Higher blood viscosity
• 5- Increased platelet aggregation
• 6- Overaggressive diuresis

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• 3-ARF pre-renal and renal
• 4- cardiovascular disease -Hyperlipidemia, may
  be a risk factor for cardiovascular disease.
• 5-Hypovolemic shock
• 6-Others growth retardation, malnutrition,
• adrenal cortical
  insufficiency

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Management of NS

• General (non-specific )
• Corticosteroid therapy

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General therapy-

• Hospitalization- for initial work-up and
  evaluation of treatment.
• Activity usually no restriction , except
• massive edema,heavy
  hypertension and infection.
• Diet Hypertension and edema Low salt
  diet (lt2gNa/ day) only during period of edema or
  salt-free diet. Severe edema Restricting
  fluid intake
• Avoiding infection very important.
• Diuresis Hydrochlorothiazide (HCT) 2mg/kg.d
• Antisterone
  24mg/kg.d
• Dextran 1015ml/kg
  , after 3060m,
• followed by Furosemide
  (Lasix) at 2mg/kg .

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Induction use of albumin-

• Albumin Lasix (20 salt poor)
• 1-Severe edema
• 2-Ascites
• 3-Pleural effusion
• 4-Genital edema
• 5-Low serum albumin

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Corticosteroidprednisone therapy-

• Prednisone tablets at a dose of 60 mg/m2/day
  (maximum daily dose, 80 mg divided into 2-3
  doses) for at least 4 consecutive weeks.
• After complete absence of proteinuria, prednisone
  dose should be tapered to 40 mg/m2/day given
  every other day as a single morning dose.
• The alternate-day dose is then slowly tapered and
  discontinued over the next 2-3 mo.

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Treatment of relapse in NS

• Many children with nephrotic syndrome will
  experience at least 1 relapse (3-4proteinuria
  plus edema).
• daily divided-dose prednisone at the doses noted
  earlier (where he has the relapse) until the
  child enters remission (urine trace or negative
  for protein for 3 consecutive days).
• The pred-nisone dose is then changed to
  alternate-day dosing and tapered over 1-2 mo.

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According to response to prednisone therapy
Remission no edema, urine is protein free for 5
consecutive days. Relapse edema, or first
morning urine sample contains gt 2 protein for 7
consecutive days. Frequent relapsing gt 2
relapses within 6 months (gt 4/year). Steroid
resistant failure to achieve remission with
prednisolone given daily for 28 days.
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Side Effects With Long Term Use of Steroids
Steroid toxicity

• hyperglycemia
• myopathy
• peptic ulcer
• poor healing of wound.
• Hirsutism
• Thromboembolism

• -Stunted growth
• Cataracts
• - Pseudotumor cerebri
• -Psycosis
• -Osteoporosis
• - Cushingoid features
• -Adrenal gland suppression

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Alternative agent-

• When can be used
• Steroid-dependent patients, frequent relapsers,
  and steroid-resistant patients.
• Cyclophosphamide Pulse steroids
• Cyclosporin A
• Tacrolimus
• Microphenolate

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• THE END.
• THANK YOU.