NEPHROTIC SYNDROME DR. R. KANDASAMY, MD, DCH PROFESSOR OF PEDIATRICS ICH &HC
NEPHROTIC SYNDROME IN CHILDREN
According to ISKDC (International Study of Kidney Disease in Children) it is defined as Proteinuria of more than 40 mg/M2/hr and Hypoalbuminaemia less than 2.5g/dl.
But for practical purposes it is defined as proteinuria more than 50 mg/kg/24 hours, serum total protein less than 5 G/dl, serum albumin less than 3 G/dl, hypercholesterolemia more than 220 mg/dl and with or without edema.
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 Scelerosis 8%
Membranous Glomerular nephrotic 1%
Mesangiocapillary Glomerular nephrotic 5%
Other proliferative lesion including Mesangial
Endocapillary and crescentric
Glomerular nephritis 3%
SECONDARY GLOMERULAR DISEASE:
Infection : - Post Infectious Glomerular nephrotis
- Infective Endocarditis
- Hepatitis B Infection
- Shunt nephrotis
Multisystem : - Henoch Schonlein purpura
- Systemic Lupus erythmatosus
- Polyarteritis Nodosa
Heredo familial - Alport Syndrome
Neoplasm : - Hodgkins’ disease
- Wilm’s tumor
Medication : - Non steroidal anti inflammatory drugs
Etiology of Idiopathic Nephrotic Syndrome is obscure.
- Immune Complexes are responsible for increasing the
- Lymphokines glomerular permeability and
- Vasoactive Amines 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 Membranopro liferative nephritis 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
In children the commonest form of N.S. is primary nephrotic 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 extremidies where it is 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.
White nails with red bands (leukonychia)
Normal Blood Pressure
No evidence of Renal failure
DIFFERENTIATION OF MCNS AND OTHER TYPES
Increased permeability to proteins
Selective proeinuria occurs
- low molecular weight proteins are excreted. Eg. Albine
- high molecular weight proteins
Eg. Lipoproteins are not excreted.
- Because more proteins are lost in the urine.
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 plasmo 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:
1. Capillaries – where there is disruption of starling equilibiria
2. Kidney – where there is primary salt retension
According to the classical view
1. Vascular underfill hypothesis
2. 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 mechanism are inadequate.
It is suggested that vascular underfill is responsible for most cases of 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 the 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 pathogenisis of NS.
Urine Culture and Sensitivity
X Ray Chest
Spot Urine Test
Calculation of selective Protenoria
= Urinary IgG /dl X Serum Albumin / dl = Less than 0.1
Serum IgG / dl Urinary Albumin / dl indicate MCNS
COMPLICATIONS DUE TO DISEASE
A. Loss of Proteins:
TMG Biochemical hypothyroidism
Vit.D Binding Globulin Hypocalcemia (Along with loss of 1,25 diOH chole calciferol)
Coagulation factors Hypercoagulable state
Loss of Immunoglobulin Acute
Depressed CMI Chronic
C. Hypercoagulable State:
- due to alteration in coagulation factors, associated infections, sepsis, Hypovolemia
i) Renal Vein Thrombosis
ii) Peripheral Vein Thrombosis
iii) Cerebral Vein Thrombosis
D. Renal Failure:
i) Chronic renal failure
- as a part of disease process.
ii) Acute renal failure
Hypovolemia induced ATN
Septicemia leading to shock and ATN
Septicemia causing bacterimia and AIN
Other drugs causing AIN
Bilateral renal vein thrombosis
Crescentic GN on existing glomerular disease like FSGS, MGN and MPGN.
i) Hypocalcemia due to loss of Ca, 1, 25 di OH Cholecalciferol, Vit.D, binding protein in urine.
iii) Renal failure – unemic
v) Cerebral Vein thrombosis
Hospitalization is necessary in the presence of
- gross oedema,
- respiratory distress
- pleural effusion
- 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.
Salt restriction is important to reduce edema. Idli, idiyappam, rice puttu, sweet pongal, coconut rice, curd rice, lemon rice, beet-root, chappathi, dhall, 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.
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.
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.
Normal protein diet is advised. In case of malnutrition increased protein is recommended.
In the acute phase of Nephrotic Syndrome nutritional intake is reduced. In malnutrition caloric supplementation is necessary.
HDL levels are elevated in MCNS. Abnormal coagulability and glomerulus recrosis are consequence of lipid abnormalities. Weight control is essential. Diet should contain cholesterol less than 250 mg/day.
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 tablet with Vit.D is necessary.
IRON & ZINC:
Iron supplementation is necessary in microcytic hypochromic anaemia. Rarely Zinc may be needed in the presence of deficiency symptoms.
Glucocorticoid has some influence 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.
Prednisolone 2 mg/kg as a single or divided doses for 4 weeks then give 2mg/kg as single dose in the morning on alternate days for the next 4 weeks. Then taper prednisolone by 10mgm 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 lable 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/kg/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, 2-3 mg/kg is given for 10 weeks.
COMPLICATIONS OF DRUGS
Pseudo tumor cerebri
Unmasking of tuberculous focus
Aseptic necrosis of femoral head
Deafness - permanent
Acute interstitial nephritis
C. Cyclophosphamide: Haemorrhagic Cystitis, Bone marrow depression, Alopecia.