The document discusses glomerular disease and nephrotic syndrome. It defines nephrotic syndrome and describes its typical manifestations. It then outlines the major causes of nephrotic syndrome including minimal change disease, membranous glomerulonephritis, and focal segmental glomerulosclerosis. For each cause, it discusses their histological classification, common features, risk of chronic kidney disease, and treatment approaches. Investigations for nephrotic syndrome and complications are also summarized.

1. Al Buick

2.  Definition
 Structure of glomerulus
 Causes
 Minimal change
 Membranous Glomerulonephritis
 Focal segmental Glomerulosclerosis
 Investigations
 Prognosis and complications
 Treatment
 Random quiz

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

4. Fenestrated
endothelial cells
Fenestrated
endothelial cells GBMGBM
Podocytes found
on Glomerular
epithelial cells
Podocytes found
on Glomerular
epithelial cells
Zip like
structure
including
from proteins
e.g. nephrin
Linker
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)

5.  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

6.  Histological classification
Nephrotic SyndromeNephrotic Syndrome
Minimal Change
Disease
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
Membranous
Glomerulonephritis

7.  Histological classification
Nephrotic SyndromeNephrotic Syndrome
Minimal Change
Disease
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
Membranous
Glomerulonephritis

9.  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

10.  Histological classification
Nephrotic SyndromeNephrotic Syndrome
Minimal Change
Disease
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
Membranous
Glomerulonephritis

11.  Histological classification
Nephrotic SyndromeNephrotic Syndrome
Minimal Change
Disease
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
Membranous
Glomerulonephritis

13.  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

14.  Histological classification
Nephrotic SyndromeNephrotic Syndrome
Minimal Change
Disease
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
Membranous
Glomerulonephritis

15.  Histological classification
Nephrotic SyndromeNephrotic Syndrome
Minimal Change
Disease
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
Membranous
Glomerulonephritis

16.  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%

17.  (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.

18.  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

19.  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

20.  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

22.  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?

23.  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

24. Any Questions

25.  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