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Glomerulonephritis

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... glomerulosclerosis, membranous nephropathy, diabetic nephropathy, minimal change ... Diabetic nephropathy most common cause ... – PowerPoint PPT presentation

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Title: Glomerulonephritis


1
Glomerulonephritis
  • Cherelle Fitzclarence
  • August 2009

1
2
Plan
  • General over view
  • Bit of revision re anatomy

2
3
Glomerulonephritis
  • Nephros kidney
  • -itis inflammation of
  • Glomus small round ball or knot
  • Pathos suffering or disease
  • -osis diseased condition
  • Glomerulonephritis inflammation of the
    glomeruli
  • Glomerulopathy disease of the glomeruli

3
4
  • Light micrograph of a normal glomerulus. There
    are only 1 or 2 cells per capillary tuft, the
    capillary lumens are open, the thickness of the
    glomerular capillary wall (long arrow) is similar
    to that of the tubular basement membranes (short
    arrow), and the mesangial cells and mesangial
    matrix are located in the central or stalk
    regions of the tuft (arrows). Courtesy of Helmut
    G Rennke.

4
5
  • Light micrograph in membranoproliferative
    glomerulonephritis showing a lobular appearance
    of the glomerular tuft with focal areas of
    increased glomerular cellularity (large arrows),
    mesangial expansion (), narrowing of the
    capillary lumens, and diffuse thickening of the
    glomerular capillary walls (small arrows).
    Courtesy of Helmut Rennke, MD.

5
6
  • Electron micrograph of a normal glomerular
    capillary loop showing the fenestrated
    endothelial cell (Endo), the glomerular basement
    membrane (GBM), and the epithelial cells with its
    interdigitating foot processes (arrow). The GBM
    is thin and no electron dense deposits are
    present. Two normal platelets are seen in the
    capillary lumen. Courtesy of Helmut Rennke, MD.

6
7
  • Electron micrograph in dense deposit disease
    (DDD) showing dense, ribbon-like appearance of
    subendothelial and intramembranous material
    (arrow) and narrowing of the capillary lumen due
    to proliferation of cells (double arrow).
    Courtesy of Helmut Rennke, MD.

7
8
Glomerular disease
  • Primary confined to the kidney
  • Secondary due to a systemic disease

8
9
Glomerular injury
  • Impairment of selective filtering properties of
    the kidney leading to a decreased GFR
  • Molecules normally not filtered such as
    constituents of the blood, pass into the urine
    and are excreted

9
10
10
11
Anatomy of Kidney
  • Note the positions of
  • Glomerulus
  • Loop of Henle
  • PCT, DCT, CT
  • Cortex, Medulla, Pelvis.

11
12
12
13
Ultrastructure Glom. capillary
13
14
Filtration Membrane Electron Micro.
14
15
Possible Clinical Manifestations
  • Proteinuria asymptomatic
  • Haematuria asymptomatic
  • Hypertension
  • Nephrotic syndrome
  • Nephritic syndrome
  • Acute renal failure
  • Rapidly progressive renal failure
  • End stage renal failure

15
16
Glomerulonephritis
  • Presence of glomerular disease as opposed to
    tubulointersititial or vascular disease is
    suspected from history
  • Haematuria (especially dysmorphic red cells)
  • Red cell casts
  • Lipiduria (glomerular permeability must be
    increased to allow the filtration of large
    lipoproteins)
  • Proteinuria (may be in nephrotic range of gt3.5
    g/24hours)

16
17
  • Phase contrast microscopy showing dysmorphic red
    cells in a patient with glomerular bleeding.
    Acanthocytes can be recognized as ring forms with
    vesicle-shaped protrusions (arrows). Courtesy of
    Hans Köhler, MD.

17
18
Diagnosis
  • Look for clues
  • History
  • Haematuria
  • Proteinuria
  • Azotemia
  • azote nitrogen
  • A without
  • Zoe life
  • The gas does not support life
  • (French chemists Gayton de Morveau
    (1737-1816) and Antoine Lavoisier (1743-1794) )

18
McCarthy ET, November 2008
19
Diagnosis
  • Can be difficult to distinguish between
    Glomerular disease and tubulo-interstitial
    disease
  • Tubular disease does not directly increase
    protein excretion but nephron loss due to the
    disease can have the same end result

19
20
Clinical patterns
  • Patients age and characteristics of the urine
    sediment can allow narrowing of the differential
    diagnosis options prior to biopsy
  • URINE IS THE LIQUID BIOPSY OF THE KIDNEY
    Walter Piering MD Prof Med Wisconsin

20
21
21
22
Urinary patterns
  • 3 different patterns
  • Focal nephritic
  • Diffuse nephritic
  • Nephrotic

22
23
Urinary patterns
  • Focal nephritic
  • Associated with inflammatory to less than half of
    the glomeruli on light microscopy
  • Red cells often dysmorphic
  • Occasional red cell casts
  • Mild proteinuria (lt1.5g/day)

23
24
Urinary Patterns
  • Diffuse nephritic
  • Damage to all or almost all of the glomeruli
  • Similar to focal disease but may also have heavy
    proteinuria (even nephrotic range), oedema,
    hypertension and/or renal insufficiency
  • - full house urinary sediment red cells,
    white cells, red cell casts, white cell casts,
    hyaline casts

24
25
Urinary Patterns
  • Nephrotic
  • Heavy proteinuria
  • Lipiduria refractile fat bodies that look like
    a maltese cross under polarised light
  • Few cells
  • Few casts but those present are hyaline and
    granular

25
26
Non specific nature of histologic patterns
  • Membranous GN usually Immune complex disease
    (infective endocarditis, SLE, Hepatitis C)
  • Membranous nephropathy drugs (gold,
    penicillamine), SLE, Hepatitis B, malignancy
  • Focal glomerulosclerosis can be primary ( minimal
    change), or secondary (intraglomerular
    hypertension, or healing previous glomerular
    injury)

26
27
Pattern diagnosis Focal GN
  • lt15 years mild post infectious GN, IgA
    nephropathy, thin basement membrane disease,
    hereditary nephritis, Henoch Schonlein Purpura,
    mesangial proliferative GN
  • 15-40 years IgA nephropathy, thin basement
    membrane disease, lupus hereditary nephritis,
    mesangial proliferative GN
  • gt40 years IgA nephropathy

27
28
Pattern Diagnosis Diffuse GN
  • Post infectious GN, lupus GN, membranoproliferativ
    e GN, mixed cryoglobulinaemia
  • Often associated with decreased complement
  • Classic findings
  • PSGN (anti strep antibodies)
  • Lupus nephritis (ANA)
  • Anti-GBM disease (anti GBM Abs)
  • Mixed cryoglobulinaemia (circulating
    cryoglobulins)
  • Wegener's granulomatosis (anti neutrophil
    cytoplasmic abs)

28
29
Pattern Diagnosis Diffuse GN
  • lt15 years Post infectious GN,
    membranoproliferative GN
  • 15-40 years Post infectious GN, rapidly
    progressive GN, fibrillary GN, membranoproliferati
    ve GN
  • gt40years rapidly progressive GN, vasculitis,
    fibrillary glomerulonephritis

29
30
Pattern Diagnosis Nephrotic syndrome
  • lt15 years minimal change disease, focal
    glomerulosclerosis, mesangial proliferative GN
  • 15-40 years focal glomerulosclerosis, minimal
    change disease, membranous nephropathy including
    lupus, diabetic nephropathy, preeclampsia, post
    infectious GN
  • gt40 years focal glomerulosclerosis, membranous
    nephropathy, diabetic nephropathy, minimal change
    disease, IgA nephropathy, primary amyloidosis or
    related disorder light chain deposition disease
    (up to 20 of pts over 60), benign
    nephrosclerosis, post infectious GN

30
31
General Workup ? Glomerular disease
  • History
  • Family history kidney disease and hearing trouble
    (Alports syndrome)
  • Medications that can damage the kidney (NSAIDs,
    ACEI, penicillamine, gold, mercury in some skin
    lightening creams)
  • Recent throat infection - ? Strep- PSGN or viral
    Wegener's granulomatosis, IgA
  • Cancer solid tumours, Hodgkins (minimal
    change) or non Hodgkins (MPGN)

31
32
General Workup ? Glomerular disease
  • Physical Examination
  • Inspection appearance, colour, pitting oedema,
    xanthelasma, alopecia, facial rash, purpura,
    clubbing, livedo reticularis
  • Palpation pulse, hepatomegaly, palpable
    kidneys, splenomegaly, palapable bladder
  • Percussion hepatomegaly, splenomegaly
  • Auscultation renal artery bruits, other bruits,
    cardiac lesions, hypertension,

32
33
General Workup ? Glomerular disease
  • Laboratory work
  • UECB
  • LFT
  • BSL
  • FBC
  • Urine microscopy and culture
  • ACR
  • Serum and urine protein electrophoresis
  • Renal ultrasound

33
34
General Workup ? Glomerular disease
  • Laboratory work
  • Specific serology
  • For a nephrotic type picture
  • HIV, HCV, HBV, ANA, serum cryoglobulins, anti DNA
    ab, complements
  • For a nephritic type picture
  • Blood cultures, ASOT, AntiDNAse B, ANA, Anti DNA
    ab, anti GBM ab, anti neutrophil cytoplasmic ab,
    complements

34
35
Case 1
  • 16 year old male
  • Presents with headache, malaise, anorexia swollen
    legs. Not peeing much. Thinks he might have put
    on some weight, belt is bit tight
  • History nasty cold with a really sore throat
    2-3 weeks ago otherwise has been well. Took a
    while to get better from the URTI

35
36
36
37
Case 1
  • Examination
  • Inspection bit pale, puffy face, oedematous
    legs
  • Palpation oedema pitting to mid thigh, nil else
    to find
  • Percussion nil to find
  • Auscultation systolic flow murmur, nil else

37
38
Case 1
  • U/A large blood, 4 protein, large leucocytes
  • Microscopy gt100 red cells, gt100 white cells,
    red and white cell casts

38
39
Case 1
  • Differential Dx at this point?
  • Post infectious GN
  • Pathogenesis is an immune reaction to certain
    pathogens, in this instance probably group A, ß
    haemolytic strep (endostreptosin and pyrogenic
    exotoxin B)
  • Throat cultures are usually negative by the time
    pt presents with GN but ASOT, antiDNAse B should
    be high along with low complements

39
40
Case 1
  • Management
  • Should get better over 2-3 weeks
  • Many cases do not present as asymptomatic
  • Supportive fluid restriction, sodium
    restriction, diuretics to help control
    hypertension
  • Modest protein restriction if the patient has
    azotemia
  • If pt not improving in a couple of weeks then
    consider biopsy
  • Biopsy will show, immune complex deposition in
    the capillary walls (immunofluorescence),
    irregular subepithelial deposits along the
    capillary loops (EM)
  • Steroids are not generally indicated but are used
    in patients who have renal failure or if the
    biopsy reveals crescents (proliferation of
    extraglomerular cells within Bowmans capsule)
    which makes for a more guarded prognosis
  • Consult Nephrologist

40
41
Case 1
  • Children usually do well
  • Adults less like to have full recovery
  • Acute GN follows other infections
  • Bacterial sepsis, acute or subacute bacterial
    endocarditis, visceral abscess, infected
    ventriculoperitoneal shunt, osteomyelitis
  • Treatment is aimed at eradicating the primary
    disease

41
42
IgA Nephropathy Buergers Disease
  • Most common cause of GN in Asia but uncommon in
    Sth America or Africa
  • 15-40 of all biopsy proven GN
  • Male gt Females
  • 2nd-3rd decade
  • Most commonly asymptomatic with serendipitous
    finding of haematuria and mild proteinuria
  • Another classic presentation is macroscopic
    haematuria in conjunction with a viral infection
  • Renal function is usually normal but occasionally
    a patient will present with acute renal failure
    due to acute tubular necrosis secondary to the
    gross haematuria
  • Biopsy mild to moderate mesangial cell
    proliferation, IgA deposits in the mesangium on
    immunofluorescence, often with C3 deposition also

42
43
IgA Nephropathy Buergers Disease
  • Slowly progressive
  • By 20 years, 50 have end stage kidney disease
  • Worse prognosis if gt1g/day proteinuria,
    hypertension, increased creatinine of glomerular
    fibrosis at biopsy, on presentation

43
44
IgA Nephropathy Buergers Disease
  • Management
  • Aggressive control of blood pressure and
    proteinuria with ACEIs or AR2Bs
  • Corticosteroids /- azathiprine varied schools
    of thought
  • However if rapidly progressive GN with crescent
    deposition treatment should be aggressive with
    high dose steroids and cyclophosphamide
  • Consult the Nephrologist

44
45
Rapidly Progressive GN (PRGN)
  • Medical emergency
  • full house nephritic urinary sediment
  • Immediate hospitalisation and biopsy
  • Crescentic GN proliferation of cells outside
    the glomerulus, but within Bowmans space
  • If IgG present in linear stain along the basement
    membrane consistent with anti glomerular
    basement membrane antibiodies (AGBM abs) which
    is a marker of Goodpastures syndrome
  • Presence of a linear pattern or complement in a
    granular pattern on the capillary wall suggests
    an immune complex associated disease such as
    lupus, IgA nephropathy of PSGN
  • Absence of immune deposition suggests a
    vasculitic process such as Wegeners
    granulomatosis or microscopic polyangiitis

45
46
RPGN eg Goodpastures
  • Autoimmune
  • Commonly 2nd-3rd decade and second peak in 60
    age group
  • Some present with renal involvement
    (Goodpastures disease)
  • Some present with pulmonary haemorrhage and
    nephritis (Goodpastures syndrome)
  • Rarely some present with only pulmonary
    involvement

46
47
Goodpastures
47
48
RPGN eg Goodpastures
  • Classic haemoptysis after upper respiratory
    infection and have nephritic urinary sediment
  • History of smoking or hydrocarbon exposure is
    common
  • CXR pulmonary haemorrhage
  • Lab- iron deficiency anaemia and renal
    dysfunction, circulating anti-GBM antibodies
  • Kidney biopsy crescentic GN with linear staining
    IgG and C3 along the glomerular basement membrane

48
49
RPGN eg Goodpastures
  • Treatment
  • High dose IV steroids (methyl pred 500mg daily
    for 3 days) followed by oral prednisolone and
    cyclophosphamide
  • Plasma exchange every other day until anti-GBM Ab
    titire is negative
  • Px guarded (if present with oliguria and elevated
    creatinine, or severe scarring unlikely to
    recover renal function)

49
50
Nephrotic Syndrome
  • Can be due to systemic or local renal disease
  • Diabetic nephropathy most common cause
  • Other common causes include amyloidosis (often
    secondary to multiple myeloma), light chain
    deposition disease, minimal change disease, focal
    segmental glomerulosclerosis, membranous
    nephropathy, membranoproliferative
    glomerulonephritis, fibrillary glomerulonephritis

50
51
Nephrotic Syndrome eg Minimal Change Disease
  • Other name lipoid nephrosis or nil disease
  • Most common cause of nephrotic syndrome in kids
    2-12 years but also in adults
  • Onset often acute and precipitant my be beesting,
    viral infection, allergy or immunization
  • Association with Hodgkins lymphoma and other T
    cell malignancies

51
52
Nephrotic Syndrome eg Minimal Change Disease
  • Clinical dramatic weight gain, pitting oedema,
    normal blood pressure. Urine proteinuria,
    hyaline casts, oval fat bodies. Usually no red
    cells. Normal renal function but sometimes
    failure secondary to severe hypoalbuminaemia or
    prerenal azotemia leading to volume contraction.
  • Children dont need biopsy unless hypertensive or
    other complications
  • If biopsy done, EM fusion of podocytes (foot
    processes of glomerular visceral epithelial cells)

52
53
Nephrotic Syndrome eg Minimal Change Disease
  • Treatment
  • Oral corticosteroids prednisolone 2mg/kg/day
  • Cyclophosphamide if relapsing diseas

53
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Nephrotic Syndrome eg FSGN
  • Most common cause of nephrotic syndrome in young
    adults
  • Classic nephrotic syndrome and a small amount of
    blood in the urine
  • Can occur in minimal change disease which becomes
    resistant to prednisolone
  • Can be secondary heroin use
  • Can be secondary to HIV infection
  • Associated with other diseases (morbid obesity,
    persistent reflux nephropathy, sickle cell
    disease , cyanotic congenital heart disease)

54
55
Nephrotic Syndrome eg FSGN
  • Diagnosis biopsy light microscopic pattern of
    segmental or total sclerosis of glomerular tufts
  • Treatment prednisolone 1mg/kg/day often for 6-8
    months
  • Complete remission only in 50
  • ACEI
  • Poor prognosticators tubulointerstitial
    disease, increased creatinine, marked proteinuria

55
56
Nephrotic Syndrome eg Membranous Nephropathy
  • Most common cause of nephrotic syndrome in 40-60
    yos
  • Usually frank nephrotic syndrome, low grade
    microhaematuria, relatively preserved renal
    function
  • Some people asymptomatic
  • Others can lose 10-20g of protein a day and be
    quite sick
  • Associated with certain medications eg
    penicillamine, gold, captopril, NSAIDs, certain
    viral infections eg Hep B and HCV and malignancies

56
57
Nephrotic Syndrome eg Membranous Nephropathy
  • Diagnosis is on kidney biopsy glomeruli appear
    normocellular with thickening of the GBM, immune
    deposits on outer side of GBM
  • Mx rule out secondary causes
  • Mx supportive ACEI/AR2B for proteinuria,
    statins for hypercholesterolaemia, prophylactic
    warfarin (if very low albumin markedly increased
    risk of venous thrombosis)
  • Prednisolone may be used
  • Some may not progress over 10 years, but marked
    proteinuria and increased creatinine 40
    progress to ESKD

57
58
Nephrotic Syndrome eg Membranoproliferative
Glomerulonephritis
  • Idiopathic if between 10-30 year
  • Between 35-60 years usually secondary to
    Hepatitis C
  • Clinical- hypertension, mild nephrotic syndrome,
    microhaematuria, relatively preserved renal
    function
  • Pts with HCV may have circulating cryoglobulins
    including triad of weakness, arthralgias and
    palpable purpura
  • In kids 2 forms
  • MPGN 1 circulating immune complexes passively
    trapped in glomeruli
  • MPGN 2 circulating IgG (nephritic factor) that
    activates complement via the alternative pathway

58
59
Nephrotic Syndrome eg Membranoproliferative
Glomerulonephritis
  • Diagnosis serum complement (depressed),
    hepatitis serologies, biopsy glomeruli are
    hypercellular, often lobular in appearance more
    detailed changes.
  • Treatment manage hypertension, ACEI/AR2B, salt
    restriction, diuretics, treat HCV with interferon
  • 50 progress to ESKD
  • Tends to recur in a kidney transplant

59
60
Nephrotic syndrome eg fibrillary
glomerulonephritis
  • Recently recognised 40-60 years
  • Similar to MPGN but serum complement normal and
    microscopy of biopsy demonstrates fibrilllar
    deposist in the mesangium.
  • Prognosis guarded

60
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Conclusions
  • Take a history
  • Do a urine test
  • If haematuria and proteinuria - ?GN
  • Exclude secondary causes
  • Biosy is the definitive way to diagnose but some
    hints from history and

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63
Acknowledgements
  • Handbook of nephrology…..Wilcox et al
  • Up to date
  • MD Consult

63
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