Nephrotic Syndrome

Al Buick

Nephrotic Syndrome Definition Structure of glomerulus Causes

Minimal change Membranous Glomerulonephritis Focal segmental Glomerulosclerosis

Investigations Prognosis and complications Treatment Random quiz

Definition

Manifestation of glomerular disease defined by: Proteinuria (>3.5g per day) Hypoalbuminaemia (< 30 g/l) Generalized oedema and

hyperlipidaemia

Structure of GlomerulusFenestrated endothelial

cellsGBM

Podocytes found on

Glomerular epithelial cells

Zip like structure including from proteins e.g. nephrinLinker proteins include podocin

1. GBM – certain collagens and heparin like molecules arranged. Size and charge selection. Albumin not pass, haemaglobin can (67,000) Myoglobin (17,000) and monomeric light chains (22,000) can pass through

2. Between podocytes a thin digapragms consisting of proteins such as nephrin(mutations of proteins such as nephrin have been found to cause some nephritic syndrome)

3. Normal urine contains small amount of protein (150mg/day)

Causes Primary glumerular disease

Minimal change Membranous glomerulonephritis Focal segmental glomerulosclerosis

Systemic Disease Diabetes SLE Amyloid

Drugs NSAIDS Penicillamine Gold

• Neoplasm• Any sold organ tumour• Leukaemia• Lymphoma

• Infection• Malaria• Streptococcal• Hep B and C• HIV

• Vascular• Malignant hypertension

CausesHistological classification

Nephrotic Syndrome

Minimal Change Disease

Focal segmental Glomerulosclero

sis

Membranous Glomerulonephriti

s

CausesHistological classification

Nephrotic Syndrome

Minimal Change Disease

Focal segmental Glomerulosclero

sis

Membranous Glomerulonephriti

s

Minimal Change

Minimal Change

Commonest cause in children 80 – 90% GN in children (20% in adults) More common in boys

Only 1% lead to chronic renal failure 80% have recurrence Responds well to treatment Associations e.g. Hodgkins

lymphoma

CausesHistological classification

Nephrotic Syndrome

Minimal Change Disease

Focal segmental Glomerulosclero

sis

Membranous Glomerulonephriti

s

CausesHistological classification

Nephrotic Syndrome

Minimal Change Disease

Focal segmental Glomerulosclero

sis

Membranous Glomerulonephriti

s

Membranous Glomerulonephritis

Membranous Glomerulonephritis

20 – 30% of nephrotic syndrome in adults (2-5%children)

Primary or idiopathic but can be secondary such as Automimmune – SLE, thyroid disease Drugs – gold, penicillamine, captopril Infection – HBV, syphilis, leprosy, filiariasis

Risk of chronic renal failure Treatment aimed at cause, can use

immunosupression Untreated 40% remission

CausesHistological classification

Nephrotic Syndrome

Minimal Change Disease

Focal segmental Glomerulosclero

sis

Membranous Glomerulonephriti

s

CausesHistological classification

Nephrotic Syndrome

Minimal Change Disease

Focal segmental Glomerulosclero

sis

Membranous Glomerulonephriti

s

Focal segmental Glomerulosclerosis

Can occur at any age Primary or secondary

Reflux IgA nephropathy Alport’s syndrome Vasculitis Sickle cell disease Heroin use HIV

50% have impaired renal function Responds to corticosteroids in 30% 30 – 50% progress to ESRF Risk of recurrence post transplant in 20 – 30%

Focal segmental Glomerulosclerosis

(A) An early lesion with segmental capillary collapse and epithelial hyperplasia (arrows).

(B and C) Glomeruli show more extensive abnormalities with on top of collapsed capillaries with epithelial hyperplasia more advanced lesions (arrowheads) with sclerosis, adhesions, epithelial hyperplasia, and mild endocapillary hypercellularity with endocapillary foam cells.

(D) A hypocellular globally sclerotic glomerulus covered with a single layer of epithelial cells, which do not appear, activated.

Investigations Urine dip

Protien ++ Granular and hyaline casts (occasional

erythrocytes) 24 urinary collection of urine , PCR

Serum albumin Serum lipid profile Serology (ASO, Antibodies, RF, ANCA, Anti

GBM) Renal ultrasound Renal biopsy

Prognosis and complications Depends on underlying disease Can be affected by degree of proteinuria,

HLA type and creatinine Complications

Hypercholesterolaemia Infection (receive oneumococcal vac) Thrombosis Renal Failure Malnutrition

Treatment

Treat underlying cause Keep blood pressure down

Corticosteroids Cyclophosphamide or ciclosporin

Minimal change Yes If frequent relapse

Membranous Based on poor prognostic factors

If renal function deteriorates

Focal segmental Yes –remission in 30%

If steroid resistant

Quiz – Who are these two?

Quiz

Linus Pauling Bright's disease 2 x Nobel prize Demonstrated that

the hemoglobin molecule changes structure when it gains or loses an oxygen

DNA triple helix?

Quiz Alonzo Harding Mourning

Played for Miami Heat

Had Focal segmental Glomerulosclerosis

Had a kidney transplant

and later won his first NBA Championship with the Heat

Thanks

Any Questions

References OHCM The renal system - Michael field, Carol Pollock,

David Harris Schieppati A, MosconiL, Perma A et al. Prognosis

of untreated patients with idiopathic membranous nephropathy. New England Journal of Medicine 1993;329: 85 -89

Tune BM, Mendoza SA. Treatment of the idiopathic nephrotic syndrome: regimens and outcomes in children and adults, Journal of the American Society of Nephrology 1997; 8: 824 - 832