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Al Buick
 Definition
 Structure of glomerulus
 Causes
 Minimal change
 Membranous Glomerulonephritis
 Focal segmental Glomerulosclerosis
 Investigations
 Prognosis and complications
 Treatment
 Random quiz
 Manifestation of glomerular disease defined
by:
 Proteinuria (>3.5g per day)
 Hypoalbuminaemia (< 30 g/l)
 Generalized oedema and hyperlipidaemia
Fenestrated
endothelial cells
GBM
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)
 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
 Histological classification
Nephrotic Syndrome
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
 Histological classification
Nephrotic Syndrome
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
 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
 Histological classification
Nephrotic Syndrome
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
 Histological classification
Nephrotic Syndrome
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
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
 Histological classification
Nephrotic Syndrome
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
 Histological classification
Nephrotic Syndrome
Minimal Change
Disease
Focal segmental
Glomerulosclerosis
Membranous
Glomerulonephritis
 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%
 (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.
 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
 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
 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
 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?
 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
Any Questions
 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

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Glomerular Disease: Causes, Investigations, and TreatmentTITLE

  • 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 GBM 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 Syndrome Minimal Change Disease Focal segmental Glomerulosclerosis Membranous Glomerulonephritis
  • 7.  Histological classification Nephrotic Syndrome Minimal Change Disease Focal segmental Glomerulosclerosis Membranous Glomerulonephritis
  • 8.
  • 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 Syndrome Minimal Change Disease Focal segmental Glomerulosclerosis Membranous Glomerulonephritis
  • 11.  Histological classification Nephrotic Syndrome Minimal Change Disease Focal segmental Glomerulosclerosis Membranous Glomerulonephritis
  • 12.
  • 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 Syndrome Minimal Change Disease Focal segmental Glomerulosclerosis Membranous Glomerulonephritis
  • 15.  Histological classification Nephrotic Syndrome Minimal Change Disease Focal segmental Glomerulosclerosis 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
  • 21.
  • 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
  • 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