Prepared by:Dr.Boshra Hasanzamani

www.mums.ac.ir/rsc-ktc

Definition of NS

Etiology of NS

Pathology of NS

Pathophysiology of NS

Clinical Manifestation of NS

Complication NS

Laboratory Data

Diagnosis

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.

Proteinuria > 3.5 g per 1.73 m2

Hypoalbuminemia

Edema

Hyperlipidemia

Lipiduria

hypercoagulability

Increase glomerular permeability for proteins due to loss of negative charged glycoprotein

-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 :

LMW+HMW are lost in urine

*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

Hyperlipidemia Increased hepatic lipoprotein synthesis

Increased urinary loss of proteins that regulate lipid homeostasis

Increase LDL and cholesterol: in the majority of patients

Increased VLDL and TG : severe disease

*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

Hypercoagulability Increased urinary loss of antithrombin III

Altered levels and or activity of proteins C and S

Hyperfibrinogenemia

Impaired fibrinolysis

Increased platelet aggregability

Spontaneous peripheral arterial or venous thrombosis – renal vein thrombosis – pulmonary embolisms

Acute RVT : Sudden onset of flank or abdominal pain

Gross hematuria

Left-sided varicocele

Increased proteinuria

Acute decline in GFR

Chronic RVT: asymptomatic

RVT :common(40%) MGN

MPGN

Amyloidosis

Other complications: Protein malnutrition

Iron-resistant microcytic hypochromic anemia (transferrin loss )

Hypocalcemia & secondary hyperparathyroidism

Depressed thyroxine levels

Increased susceptibility to infection Low levels of IgG

Changes in the pharmacokinetics of drug

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.

B-Secondary NS:

NS resulted from systemic diseases, such as anaphylactoid purpura , systemic lupus erythematosus, HBV infection.

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, Hashimoto’s thyroiditis,, HSP, Vasculitis

Metabolic disease: Diabetes mellitus

Neoplasma: Hodgkin’s 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

Primary glomerulonephritis

Minimal change disease

Focal segmental glomerulosclerosis (most common cause in adults)

Membranous glomerulonephritis

sometimes known as nil lesion

causes 70–90% of nephrotic syndrome in childhood but only 10–15% of nephrotic syndrome in adults

usually presents as a primary renal disease

can be associated with several other conditions, including :

- Hodgkin's disease

- allergies

- use of nonsteroidal anti-inflammatory agents;

(significant interstitial nephritis often accompanies

cases associated with nonsteroidal use )

on renal biopsy shows :

L.M :

- no obvious glomerular lesion

I.F :

- negative for deposits

- or occasionally shows small amounts of IgM in the

mesangium

E.M :

- effacement of the foot process supporting the epithelial

podocytes with weakening of slit-pore membranes

Table 274-1. Major Causes of Minimal Change Disease (Nil Disease, Lipoid Nephrosis)

Idiopathic (majority)

In association with systemic diseases or drugs

Drug-induced interstitial nephritis induced by NSAIDs, rifampin, interferon a

Hodgkin's disease and other lymphoproliferative malignancy

HIV infection

NOTE: NSAIDs, nonsteroidal anti-inflammatory drugs.

IN MCDS , The male preponderance of 2:1

: 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)

acellular urinary sediment

Average urine protein excretion reported in 24 hours is 10 grams with severe hypoalbuminemia

Less common clinical features include :

- hypertension (30% in children, 50% in adults)

- microscopic hematuria (20% in children, 33% in

adults)

-atopy or allergic symptoms (40% in children, 30% in

adults)

-decreased renal function (<5% in children, 30% in adults)

Idiopathic (majority)

In association with systemic diseases or drugs

HIV infection

Diabetes mellitus

Fabry's disease

Sialidosis

Charcot-Marie-Tooth disease

As consequence of sustained glomerular capillary

hypertension

Congenital oligonephropathies

Unilateral renal agenesis

Oligomeganephronia

Acquired nephron loss

Surgical resection

Reflux nephropathy

Glomerulonephritis or tubulointerstitial nephritis

Other adaptive responses

Sickle cell nephropathy

Obesity with sleep apnea syndrome

Familial dysautonomia

Miscellaneou

Heroin use

LM: Sclerosis with hyalinosis – intrapment of amorphouse hyaline material

EM:damage of visceral epithelial cell

30-40%nephrotic syn. In adults

Rare cause in children

Peak incidence:30 – 50 years

Male – female ratio: 2:1

LM:diffuse thickening of GBM

IF:granular deposition of IgG – C3 – CH50 along the glomerular capillary wall

>80% nephrotic syn.

Microscopic hematuria:50%

HTN:10-30%

ANA-ANCA-anti-GBM-cryoglobulin-comlement: Negative

One-third occurs in association with systemic dis.

Conditions Associated with Membranous

Glomerulopathy

Idiopathic (majority)

In association with systemic diseases or drugs

Infection

Hepatitis B and C, secondary and congenital syphilis,

malaria, schistosomiasis, leprosy, hydatid disease,

filariasis, enterococcal endocarditis

Systemic autoimmune diseases

SLE, rheumatoid disease, Sjogren's syndrome,

Hashimoto's disease, Graves' disease, mixed connective

tissue disease, primary biliary cirrhosis, ankylosing

spondylitis, dermatitis herpetiformis, bullous pemphigoid,

myasthenia gravis

Neoplasia

Carcinoma of the breast, lung, colon, stomach, and

esophagus; melanoma; renal cell carcinoma;

neuroblastoma; carotid body tumor

Drugs

Gold, penicillamine, captopril, NSAIDs, probenecid,

trimethadione, chlormethiazole, mercury

Miscellaneous

Sarcoidosis, diabetes mellitus, sickle cell disease,

Crohn's disease, Guillain-Barre syndrome, Weber-

Christian disease, Fanconi's syndrome, a1

antitrypsin deficiency, angiofollicular lymph node

hyperplasia

Spontaneous remission :40%

Relapses and remission:30-40%

Slow progressive decline in GFR:10-20%

Poor prognosis: HTN

Severe proteinuria and hyperlipidemia

Impaired renal function

Older age

Male gender

MESANGIOCAPILLARY GN

LM: thickening of the GBM and proliferative changes

Two major types Both:diffuse increase in mesangial cellularity and matrix

Thickening and reduplication of the GBM

DDX- EM: TYPE I :subendothelial and mesangial deposits contain IgG or

IgM and C3

Type II (dense deposit disease):

Electron –dense deposits within the GBM

Type I :immunecomplex GN Heavy protenuria and nephrotic syn.

Active urinary sediment

Normal or mildly impaired GFR

C3 depressed

C4 and C1q :borderline or low

ESRD:50% by 10 years

No proven therapy

Type II : autoimmune disease

Nephrotic syn.

RPGN

Recurrent macroscopic hematuria

Have an IgG autoantibody(C3 nephritic factor)

No effective therapy

Causes of Membranoproliferative

(Mesangiocapillary) Glomerulonephritis

(MPGN)

Idiopathic

Type I

With subendothelial and mesangial immune deposits

Type II

With intramembranous dense deposits containing sparse

or no Ig; associated with C3 nephritic factor

Type III

Features of type I MPGN and membranous

nephropathy

Systemic immune-complex disease SLE, mixed cryoglobulinemia, Sjogren's syndrome

Chronic infections Hepatitis B and C, HIV, bacterial endocarditis,

ventriculoatrial shunts, visceral abscess

Malignancy Leukemias, lymphomas

Liver disease Chronic active hepatitis and cirrhosis (usually associated

with hepatitis B or C)

Miscellaneous Partial lipodystrophy, heroin use, sarcoidosis, inherited C2

deficiency, thrombotic microangiopathies

Edema

Hyperlipidemia

Hypercoagulability

Anemia

Hyperfibrinogenemia

transferrin loss

Oncotic pressure

lipoprotein synthesis