Nephrotic syndrome is classified as Primary Glomerular disease and Secondary Glomerular disease. Histopathologically, primary or idiopathic Nephrotic Syndrome are classified as:

• Minimal Change Nephrotic Syndrome
• Focal Glomerular Sclerosis
• Diffuse Glomerular Sclerosis
• Membranous Glomerular Nephrotis
• Mesangio Capillary Glomerular Nephrotis
• Mesangial Proliferative Glomerular Nephrotis
• Endo Capillary Proliferative Glomerular Nephrotis
• Other Chronic Sclerosing Lesion
• Other Unclassified Disease

THE PREVALENCE OF PRIMARY NEPHROTIC SYNDROME

(Due to primary glomerular disease according to Cameron and Co-workers is given below)

LESION                         % OF PREVALENCE

Minimal Change                           83%

Focal Glomerular Sclerosis         8%

Membranous Glomerular           1%

Nephrotic

Mesangiocapillary Glomerular   5%

Nephrotic 

Endocapillary and Crescentric    3%

Glomerular Nephritis

SECONDARY GLOMERULAR DISEASE

Infection:    

Post infective Glomerular Nephrotitis, Infective Endocarditis, Hepatitis B Infection, Shunt Nephrotis and Malaria

Multisystem: 

Henoch Schonlein Purpura, Systemic Lupus Erythmatosus and Polyarteritis Nodosa

Heredo Familial Neoplasm:

Alport Syndrome, Hodgkin’s disease, Leukemia and Wilm’s tumor

Medication:

Non Steroidal anti inflammatory drugs, Anti Convulsants Like phenytoin, Trimethadione, Pencillamine, Allergens, Serum Sickness Toxoid, Food allergens, Insect Bites.

ETIOLOGY

Etiology of Idiopathic Nephrotic Syndrome is obscure.

PATHOGENESIS

Lymphocytoxins, Immune Complexes, Lymphokines and Vasoactive Amines – They are responsible for increasing the glomerular permeability and Proteinuria

T Cell – Dysfunction is the modern thinking. It is observed in Hodgkin’s disease

In Focal Glomerular Sclerosis – Immune Complexes, IgM and C have been identified

MCNS – has been linked with HLA B12, HLA B8 and HLA DR7

In Membrane Proliferative Nepthritis the role of Hepatitis B antigens in have been demonstrated

MCNS – Electron Microscopy reveals the glomeruli appear normal on

Minimal increase in mesangial cell and matrix

Retraction of the epithelial cell foot process

FGG – Focal Glomerular Sclerosis

• Majority of glomerulo appear normal or manifest mesangial proliferation

CLINICAL FEATURES

• In children the commonest form of N.S. is primary nephritic syndrome
• Among these the MCNS is the most frequent
• Insidious onset of odema
• Mild fever and Cold
• Many children have recurrent episodes of such transient edema for many months
• Physical examination shows

Edema – The edema is initially noted around the eyes and in the lower extremities where it pitting in nature, with time edema becomes generalized and may associate with weight gain and the development of ascites, pleural effusion and decreased urinal output

Pallor

White nails with red bands (leukonychia)

Normal Blood Pressure

No evidence of Renal Failure

PATHOPHYSIOLOGY

MASSIVE PROTEINURIA:

• Increased permeability to proteins
• Selective proteinuria to proteins

Low molecular weight proteins are excreted e.g. Albine

High molecular weight proteins e.g. Lipoproteins are not excreted

HYPOALBUMINAENIA:

• Because more proteins are lost in the urine

EDEMA

Fluid movements across capillary is normally the result of a balance between filteration and reabsorption, due to changes in capillary and tissue hydrostatic and oncotic pressure. It is still the pathogenesis of edema in NS is not well understood.

Because of the hypoalbuminaenia, there is reduction in plasma oncotic pressure leads to leak of fluid in to the interstitial compartment or accumulation of fluid secondary to sodium due to internal defect

The major sites involved in the edema formation are:

Capillaries – where there is disruption of starling equilibria

Kidney – where there is primary salt retension

According to the classical view

         Vascular underfill hypothesis

         Vascular overfill hypothesis

Vascular underfill hypothesis is responsible for the formation of edema

VASCULAR OVERFILL HYPOTHESIS

• Primary intra renal defect in sodium handling is responsible for occurrence of edema
• This results in decreased filteration per nephron, increase in tubular reabsorption and decreased sensitivity to atrial netriuretic peptide leading to fluid retension

Finally the human body is equipped with defence mechanism that limits excessive capillary fluid filteration

These defense mechanism includes increased interstitial hydrostatic pressure and lymph flow, decreased interstitial oncotic pressure and reduced permeability of the capillaries to protein.

EDEMA RESULTS WHEN THESE ADOPTIVE MECHANISMS ARE

• Inadequate
• It is suggested that vascular underfill is responsible for most cases in edema in MCNS. Other mechanisms might be important in patients with non MCNS.
• There is increasing evidence of hypoalbumia and the inability of the renal distal tubules to excret sodium are not only factor responsible for the occurrence of edema.
• Internal vascular capillary permeability related to the release of vascular permeability factor and other cytokines may also play a important role in the pathogenesis of NS.

INVESTIGATIONS

Hb %

TC

DC

Mx

Urine Examination

Urine Culture and Sensitivity

X Ray Chest

USG Abdomen

Serum Proteins

Urinary Proteins

Spot Urine Test

Serum Cholesterol

Selective Proteinuia

Kidney Biopsy

COMPLICATIONS DUE TO DISEASE

• Loss of Proteins

               Albumin  – Edema

               Transferrin – Anemia

               TMG – Biochemical hypothyroidism

               Vit. D Binding Globulin – Hypocalcemia (Along with loss of Chole calciferol)

Immunoglobulin – Infection

Coagulation factors – Hypercoagulable state

1. Infection:

Loss of Immunoglobulin – Acute

Depressed CMI – Chronic

1. Hypercoagulable State: Due to alteration in coagulation factors, associated infections, sepsis, Hypovolemia.

Renal Vein Thrombosis

Peripheral Vein Thrombosis

Cerebral Vein Thromobosis

Chronic Renal failure

1. Renal Failure
2. Convulsions

TREATMENT

1. Hospitalization is necessary in the presence of gross oedema,

Respiratory distress

Pleural effusion

Peritonitis

Unexplained fever

2. Bed rest is essential in gross edema
3. Salt and fluid restriction depend upon oedema
4. Diuretic is a double edged weapon, so it should be used with caution
5. Hydrochlorthizide would suffice in mild and moderate edema given as 4 mg/kg in a single dose.
6. Spiranolactone should be combined with these diuretics.

DIET

Salt restriction is important to reduce edema. Idli, idiyapam, rice puttu, sweet pongal, coconut rice, curd rice, lemon rice, beet-root, chappathi, dhal, sugar candy, boiled potato, carrot, cabbage, tomato and onion are accepted. Start with salt free diet in the presence of edema and then slowly add salt.

WATER

Along with salt restriction, water restriction is necessary to prevent dilutional hyponatremia. In mild edema, intake is restricted to the urine output. In moderate edema, intake is restricted to insensible water loss. In massive edema fluid intake is restricted to milk only equivalent to insensible water loss.

POTASSIUM

• Serum potassium abnormalities are infrequent in NS without renal failure
• Hypokalemia is the consequence of indiscriminate diuretics
• Add oral potassium in the presence of excessive tiredness or muscle weakness
• Periodic serum potassium level estimation will be useful

PROTEIN

Normal protein diet is advised. In case of malnutrition increased protein is recommended

CALORIES

In the acute phase of Nephrotic syndrome nutritional intake is reduced. In malnutrition, caloric supplementation is necessary.

LIPID

HDL levels are elevated in MCNS. Abnormal coagulability and glomerulus necrosis are consequence of lipid abnormalities. Weight control is essential. Diet should contain cholesterol less than 250 mg/day

CALCIUM

Secondary to hypoalbuminemia, there is low ionic calcium, which is responsible for cramps and tetany. Hence calcium intake of 800 mg/day either by diet or tabet with Vit. D is necessary.

IRON AND ZINC

Iron supplementation is necessary in microcytic hypochromic anaemia. Rarely, Zinc may be needed in the presence of deficiency symptoms.

Glucocorticoid has some influences on glomerular permeability. It blocks the action of migratory inhibiting factor (MIF) and chemotactic factor, inhibits the endothelial adherence of macrophages and leukocytes, blocks the antigen processing function of macrophage, stabilizes lysosomal membrane and prevents the increase in capillary permeability and diapedesis.

INITIAL THERAPY

Prednisolone 2 mg/kg as a single or divided doses for  4 weeks then give 2 mg/kg as single dose in the morning on alternative days for the next 4 weeks. Then taper prednisolone by 10 mg every 2 weeks. If there is persistent proteinuria even after four weeks of daily therapy of steroid, continue the same dose for the next 4 weeks. If there is no remission even after 8 weeks of full dose of steroids, then label the child as steroid resistant. In this type of cases, steroids should be tapered to 0.5 mg/kg. simultaneously add cyclophosphamide in a dose of 2 mg/day. Care should be taken to have weekly W.B.C count.

In case of steroid response but when there is frequent relapse prednisolone is to be given as 2 mg/kg for 4 weeks and then as a single dose in the morning on alternate day for 4 weeks. After 8 weeks of steroid therapy, it should  be tapered but slowly so that the entire course lasts for 6 months. When the child is resistant to Predinosolone and Cyclophosphamise, Chlorambucil, 2 to 3 mg/kg is given for 10 weeks.

COMPLICATIONS OF DRUGS

• Steroids

Pseudo tumor cerebri

Cataract

Cushingoid facies

Unmasking of tuberculous focus

Peptic ulcer

Diabetes mellitus

Hypertension

Aseptic necrosis of femoral head

1. Frusemide

Hypokalemia

Hyponatremia

Hyperuricemia

Hypercalciuria

Hypocalcemia

Hypovolemia

Tinnitus

Deafness – Permanent, Temporary

Acute Interstitial nephritis

1. Cyclophosphamide

Haemorrhagic Cystitis

Bone Marrow Depression

Alopecia

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