⭐NEPHROTIC SYNDROME ⭐

July 04, 2021

A disorder of kidney which is characterized by Proteinuria, Oedema, Hypoalbuminemia ,Hyperlipidemia and sometimes Hypertension.

( #Proteinuria - presence of abnormal quantities of protein in urine.

# Hypoalbuminemia - decreased levels of

albumin in blood.

# Oedema - swelling caused by build up

of fluid.

# Hyperlipidemia - Increased levels of

lipids in blood.

# Hypertension - high blood pressure.)

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1) PATHOPHYSIOLOGY of nephrotic syndrome:-

(A) In nephrotic syndrome, there is

increase in permeability of

glomerular capillaries which leads to

proteinuria.

This increase in permeability may be

due to :-

(I) Glomerular inflammation - there is

damage to glomeruli due to

cytokines and permeability factors

released during inflammation.

(II) Change in charge of GBM i.e

glomerular basement membrane.

- Normally it has net negative

charge and hence repels

negatively charged albumin.

- change in charge can lead to

decreased repulsion and hence

can cause proteinuria.

(III) # Change in size of filtration slits

in Bowman's capsule -

( Podocytes are specialized cells

lining visceral layer of Bowman's

capsule. Foot processes of

podocytes wrap themselves

around capillaries of glomerulus

to form filtration slits through

which ultrafiltration of blood

occurs.)

# Increase in the size of filtration

slits leads to filtration of proteins

like albumin.

# This increase in size occurs due

to deformation of podocyte foot

processes which may occur due

to mutation of podocyte proteins.

(B) # Proteinuria - Occurs due to

increased glomerular permeability.

# Hypoalbuminemia - due to loss of

albumin through urine.

# Oedema - Due to decreased level

of albumin in blood, plasma oncotic

pressure decreases and fluid goes

from intravascular compartment to

extravascular compartment leading

to oedema.

# Hyperlipidemia - Due to

(I) Hypoalbuminemia causes

upregulation of HMG CoA

reductase enzyme which is involved

in cholesterol synthesis and it also

causes downregulation of enzyme

lipoprotein lipase which degrades

lipoprotein. Thus, lipids increase

leading to Hyperlipidemia.

(II) Kidneys are major site of

metabolism of mevalonate ,a

precursor in cholesterol synthesis.

This metabolism and excretion of

mevalonate is impaired in

nephrotic syndrome due to

damage to kidney. Hence,

increased mevalonate causes

increased cholesterol synthesis in

liver leading to Hyperlipidemia.

# Hypertension - It may occur sometimes due to RAAS activation as intravascular volume decreases due to shift of fluid into extravascular compartment.

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2) EFFECTS OF LOSS OF PROTEINS in

Nephrotic syndrome :-

(A) Due to loss of thyroxine binding

protein - thyroid problems may occur.

(B) Loss of calciferol binding protein-

Vit D deficiency may occur.

metal deficiency.

(D) Loss of transferrin - anemia

( Transferrin helps in iron transport)

(E) Loss of drug binding protein-

defective pharmacokinetics of drugs

(F) Loss of albumin - leads to edema,

ascites, pleural effusion, subungual

edema ( beneath nail beds)

(G) Loss of Globulin- decreased formation of IgG leading to bacterial

peritonitis.

(H) Loss of antithrombin- Hypercoagulable state, renal vein thrombosis.

(Other causes of hypercoagulable state= Altered levels of protein C & S), increased hepatic production of fibrinogen.)

Renal vein thrombosis can cause flank

pain, hematuria, MI, stroke, pulmonary embolism

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3) CAUSE Of Nephrotic syndrome:-

(A) Primary Glomerular Disease (Idiopathic)=

i) Minimal Change Disease: Most common cause of nephrotic syndrome in children which is caused due to effacement (erased or blotting out )of podocyte process.

(Foot processes of podocytes spread & form mesh like network. Pores in between them form filtration slits. In minimal

change disease, there is altered T cell mediated immunological response leading to abnormal secretion of lymphokines by T cells causing effcaement of foot processes. Hence, steroids are given to suppress this immune response.)

ii) Focal & Segmental Glomerulosclerosis.

iii) Membranous GN.

iv) Mesangial Proliferative Glomerulonephritis.

B) Secondary Causes=

i) Infections:

(Can cause kidney injury by direct invasion or by cytokine based & immune based mechanism leading to increased glomerular permeability).

HIV, syphilis, Hep B, Malaria, Leprosy, infective endocarditis.

ii) Tumors: Hodgkin's Lymphoma, Carcinoma, Leukemia.

(Due to infiltration of tumor cells in kidney, inflammation & increased permeability may occur. Also tumor antigen deposition may occur.)

iii) Metabolic:

#Diabetes (Increased blood glucose leads to increased blood flow to the kidney for increased excretion of glucose leading to strain & damage to glomeruli.)

#Amyloidosis.

iv) Connective tissue disorders:

SLE, Rheumatoid Arthritis.

(Autoantibodies affect kidney leading to inflammation.)

v) Drugs & toxins:

(cause inflammation to kidney)

Heroin, Mercury, Gold, Penicillamine, Captopril.

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4) INVESTIGATIONS of nephrotic syndrome:-

A) 24 hr urinary protein measurements=

(detects proteinuria).

B) Serum Albumin=

(Detects hypoalbuminemia).

C)Serum Cholesterol=

(Detects hyperlipidemia).

D) Sometimes Red cell casts may be present in urine microscopy.

E) Renal biopsy.

F) Appropriate investigations for secondary causes.

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5) TREATMENT of nephrotic syndrome:-

A) t/t for proteinuria=

i)ACE inhibitors :

(MOA= Normally, Angiotensin II causes efferent arteriolar vasoconstriction which causes increased glomerular hydrostatic pressure leading to proteinuria. ACE inhibitors prevents this by causing afferent & efferent vasodilation).

ii)NSAIDS:

(MOA= Prostaglandins cause afferent arteriolar vasodilation causing increased amount of blood reaching glomeruli and thus increasing glomerular blood pressure. NSAIDS prevent PG production and hence cause afferent arteriolar vasoconstriction thus decreasing glomerular blood flow. However risks of vasoconstriction are ARF, hyperkalemia, salt retention).

B) t/t for preventing complications=

i)Vit. D = treats deficiency .

ii) Anticoagulants = for thrombosis.

iii) Cholesterol lowering drugs = for hyperlipidemia.

iv) Dietary protein = 0.8 to 1 g/kg, not more to prevent renal failure.

v) Salt restriction & diuretics = treats edema.

vi) Sometimes i.v. Albumin is given.

C) t/t of Cause=

i)Minimal Change Disease:

In patients, Corticosteroids like Prednisolone in a dose of 60 mg/m2 daily for 4 weeks & 35 mg/m2 on alternate day for next 4 weeks.

a)Children who respond: Steroid Responders.

b)Children who show relapse on withdrawal of drug: Steroid dependent syndrome. They are given drugs as initial regimen & there by tapering regimen very slowly.

c)Other drugs: Cyclosporine, Tacrolimus, Cyclophosphamide.

ii) Membranous GN: Steroids in combination with cyclophosphamide & cyclosporine.

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