Transcript GLOMERULOPATHY clinical categories

GLOMERULOPATHY
clinical categories
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Acute nephritic syndrome:
haematuria, red blood cell casts,
proteinuria, oliguria, hypertension, edema,
circulatory congestion
Rapidly progressive nephritic syndrome:
relentlessly progressive glomerulonephritis
resulting in ESRF within weeks
Recurrent gross haematuria
GLOMERULOPATHY
clinical categories
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Asymptomatic glomerulopathy:
proteinuria, haematuria, or both – without
clinical symptoms
Chronic nephritic (glomerular) syndrome:
glomerular disease that progress in chronic
renal failure
Nephrotic syndrome
GLOMERULOPATHY
structural characteristics
➲Acute
damage (diffuse or segmental):
- proliferation of epithelial, endothelial and
mesangial cells;
- exudation of polymorphonuclear leukocytes
in the glomerulus;
- necrosis of glomerular capillaries
GLOMERULOPATHY
structural characteristics
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Chronic damage:
- proliferation of cellular elements
(epithelium, endothelium, mesangium);
- membranous involvement with thickening
of glomerular basement membrane
(GBM);
- sclerosis of the glomerulus;
- tubular atrophy, nephrosclerosis,
interstitial scarring (in ESRF)
GLOMERULOPATHY
pathogenesis
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Immunologic reactions
Vascular diseases
Abnormalities in coagulation
Metabolic defects
Hereditary factors
Unknown factors
GLOMERULOPATHY
immunologic mechanism
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Circulating immune complex – mediated
disease
Antitissue antibody – mediated disease
Cell- mediated disease
Disease associated with activation of
alternative complement pathway
Physiology of protein excretion
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Protein filtration through the glomerulus is
dependent on the protein size, shape and
electrical charge
Physiology of protein excretion
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Protein charge
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At physiological pH, most proteins are
negatively charged
●
Since the basement membranes are also
negatively charged, most proteins are
retained
Physiology of protein excretion
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Protein size
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Proteins greater than 40kDa are almost
completely retained
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Thus, only small proteins, e.g. retinolbinding protein, ß2 microglobulin, passes
into the ultrafiltrate
Physiology of protein excretion
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However, most of the filtered proteins are
reabsorbed by the proximal tubules.
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Consequently, very little plasma protein
appears in the urine
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Normally < 150mg/24hours
“Physiological” proteinuria
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In some non-pathological situations, a higher
than normal urine protein level is found:
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A concentrated spot urine
Exercise
Orthostatic proteinuria
Contamination e.g. from vagina
Classification
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Tubular proteinuria
● Tubular dysfunction
● Overflow proteinuria
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Glomerular proteinuria
● Selective proteinuria
● Non-selective proteinuria
● microalbuminuria
Tubular proteinuria
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This occurs when glomerular function is
intact, but protein is lost to the urine either
because of:
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Tubular dysfunction
Overflow
Tubular proteinuria
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Tubular dysfunction
● The tubules are damaged and cannot function
properly
● Therefore, the small MW proteins that are
normally filtered are not reabsorbed by the
tubules
● The small MW proteins include: retinolbinding protein, ß2 microglobulin, lysozyme,
light chains, haemoglobin, myoglobin
Tubular proteinuria
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Tubular dysfunction
● Pyelonephritis
● Acute tubular necrosis
● Papillary necrosis e.g. analgesic
nephropathy
● Heavy metal poisoning
● SLE
● Fanconi’s syndrome
Tubular proteinuria
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Overflow proteinuria
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Occurs when the concentration of one of
the small MW proteins is so high that the
filtered load exceeds the tubular
reabsorptive capacity
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Thus, the excess filtered load appears in
the urine
Tubular proteinuria
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Overflow proteinuria
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Bence Jones proteinuria
Myoglobinuria
Haemoglobinuria
Glomerular proteinuria
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When there is glomerular dysfunction,
proteins > 40kDa can escape into the urine
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The most common form of proteinuria
Glomerular proteinuria
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Causes
● Glomerulonephritis
● Diabetes mellitus
● Multiple myeloma
● Amyloidosis
● SLE
● Pre-eclampsia
● Penicillamine, gold
Definitions
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Proteinuria
● Urine protein excretion > 150mg/day
➲ Microalbuminuria
● Urine [albumin] > 30mg/day but not detectable
by urine dipstick
➲ Nephrotic syndrome
● Urine protein excretion > 3.5g/day (with
hypoalbuminaemia, oedema and
hyperlipidaemia)
Nephrotic Syndrome (NS)
 Is
not a disease but a group of signs and
symptoms seen in patients with heavy
proteinuria
 presents with oedema
 proteinuria usually > 3.5g / 24hrs (>0.05g / kg /
24hrs in children)
 serum albumin < 30g/l
 other features: hyperlipidaemia, and
hypercoaguable state
NS pathophysiology
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proteinuria: due to an increase in glomerular
permeability
hypoalbuminuria: occurs when liver synthesis cannot
keep up with urine losses
 oedema mechanism is complex and still in dispute:
primary salt and water retention associated with
reduced renal function as well as reduced plasma
oncotic pressure are primary factors (overfill and
underfill)
hyperlipidaemia: increased liver synthesis
hypercoagulation: increased fibrinogen and loss of
antithrombin III
Clinical Features in NS Thrombosis
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Serious risk of thrombosis
Increased fibrinogen concentration
Antithrombin III concentration reduced
NS patients resistant to heparin
Platelets hyperaggregable
Increased blood viscosity
NS - laboratory Features
➲ Hct may be elevated
➲ Hyponatremia is common
➲ Plasma creatinine is elevated
33% of patients
in
NS laboratory- Plasma Protein
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Albumin
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Hypoalbuminemia due to loss via the kidney
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Urinary excretion
Proximal tubular cells catabolism
Immunoglobulins
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IgG levels reduced
IgM levels elevated
IgM-IgG-Switching
NS laboratory- Hyperlipidemia
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Increased synthesis of cholesterol,
triglycerides and lipoproteins
➲ Decreased catabolism of lipoproteins
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Decreased activity of lipoprotein lipase
Decreased LDL receptor activity
Increased urinary loss of HDL
Lp(a) levels are elevated
Primary glomerular diseases commonly
causing the nephrotic syndrome
 minimal change disease
 focal and segmental glomerulosclerosis
 membranous glomerulonephritis
 proliferative glomerulonephritis (various
histology and less common cause)
 membranoproliferative (mesangiocapillary)
 focal proliferative
 diffuse proliferative
 mesangial proliferative
Other causes of the nephrotic syndrome 1
 Systemic diseases
 diabetes mellitus
 amyloidosis
 SLE and other connective
 HIV/AIDS
 nephrotoxins
 nsaids
 mercury poisoning
 penicillamine
 gold salts
tissue diseases
Other causes of the nephrotic syndrome 2
 Allergies
 bee sting
 pollens
 poison ivy
 Circulatory effects
 congestive cardiac failure
 constrictive pericarditis
 renal vein thrombosis (cause
 Neoplastic
 leukaemia
 solid tumours
or result?)
NS epidemiology
NS treatment- Diet
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Low protein
● Decreases albuminuria
● Malnutrition
➲ Salt restriction (Na+< 60 mmol/24 hrs)
● During edema
➲ Calorie control
● Steroids
NS treatment
 water restriction
 diuretics (if not volume depleted)
 reduced protein diet (controversial)
 treat infections
 prophylaxis for thrombosis
 specific therapy
 corticosteroids
 immunosuppression
NS treatment- Albumin
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Controversial
Indication- Hypovolemia
● Abdominal pain
● Hypotension
● Oliguria
● Renal insufficiency
NS complications
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Mortality
● 1940’s- 40% 1 year mortality
● Now 1-2%
● Main cause of death
● Infection
● Thrombosis
Corticosteroids Initiation in NS
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High dose steroids
● 2 mg/kg/day (max 80 mg)
● 60 mg/m2 (max 80 mg)
➲ 3 accepted protocols
➲ 80% respond within 2 weeks
Steroid Toxicity
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Cushingoid habitus
Obesity
Striae
Hirsutism
Acne
Growth failure
Avascular necrosis
Osteoporosis
Steroid Toxicity
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Peptic ulceration
Pancreatitis
Posterior lens opacities
Myopathy
Increased ICP
Susceptibility to infection
Options for Alternative Therapy
in NS
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Alkylating Agents
● Nitrogen mustard
● Cyclophosphamide
● Chlorambucil
➲ Levamisole
➲ Cyclosporine
Indications for Alternative Therapy
in NS
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Relapse on Prednisone Dosage >0.5
mg/kg/alt day plus:
● Severe steroid side effects
● High risk of toxicity- diabetes
● Unusually severe relapses
➲ Relapses on Prednisone Dosage >1.0
mg/kg/alt day
Acute Nephritic Syndrome
 Syndrome
characterised in typical cases by:
 haematuria
 oliguria
 oedema
 hypertension
 reduced GFR
 proteinuria
 fluid overload
Clinical Features of the Acute Nephritic
Syndrome
 haematuria
is usually macroscopic with pink or
brown urine (like coca cola)
 oliguria may be overlooked or absent in milder
cases
 oedema is usually mild and is often just periorbital- weight gain may be detected
 hypertension common and associated with
raised urea and creatinine
 proteinuria is variable but usually less than in
the nephrotic syndrome
Etiology of the Nephritic Syndrome
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Most common cause is acute post infectious
glomerulonephritis
group A beta haemolytic streptococci of certain
serotypes important in NZ
IgA disease and Henoch-Schonlein purpura,
crescentic glomerulonephritis and SLE can
also present in this way
Complications of the Nephritic
Syndrome
 Hypertensive
 Heart
encephalopathy (seizures, coma)
Failure (pulmonary oedema)
 Uraemia
requiring dialysis
Acute poststreptococcal GN
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Archetype of acute nephritic syndrome
Proliferative character
Only certain varietes of beta-hemolytic
streptococci (nephritogenic strains) induce
abnormalities in kidneys
Production of nonspecific evidence of
streptococcal exposure (elevated
antistreptolisin titers)
Antibody production and immune
complexes
Acute poststreptococcal GN
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Kidneys are enlarged, edematosus, pale
Electron-dense deposits on the epithelial
side of GBM
Reduced GFR
Elevation of urea and creatinine is
characteristic
Urine: reduced in volume, concentrated,
reddish brown; contains as much as 2 to 4
mg/day of protein
Acute poststreptococcal GN
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More common in males than females and
most frequent between the ages of 3 and 7
years
Classically, 10 days after sore throat
Acute nephritic syndrome
Gross hematuria and fever
Worse prognosis in adults
Definition of glomerulonephritis
Glomerulonephritides are supposedly
immunologically mediated
glomerular diseases,
often, but not always,
inflammatory in nature
Glomerular inflammation
1.
Exsudation of neutrophils and/or
macrophages
2. Proliferation of mesangial and/or
endothelial cells
Ultrastructural changes in non-proliferative vs. proliferative
glomerulonephritides
Mechanisms of glomerular damage
Simplified classification of primary
glomerulonephritides
1. Nonproliferative
- minimal change disease
- focal segmental glomerulosclerosis
- membranous nephropathy
2. Proliferative
- IgA nephropathy
- membranoproliferative GN
Ultrastructural changes in glomerular capillaries in different
glomerular diseases
Podocytes and slit diaphragms
Major causes of podocyte effacement
Slit diaphragm and its lipid raft
nephrin, podocin
1. Podocyte cytoskeleton
-actinin
1. Adhesion of podocyte to GBM
 -dystroglycan, 1-integrins
4. Loss of podocyte electronegative charge
podocalyxin
1.
Non-proliferative glomerulopathies
Damage to the glomerular capillary wall resulting
in:
1. nephrotic selective proteinuria
- minimal change disease
2. nephrotic non-selective proteinuria with
microscopic hematuria
- focal segmental glomerulosclerosis
- idiopathic membranous nephropathy
Primary glomerulonephritides as a cause of nephrotic syndrome
Korbet et al., Am. J. Kidney Dis., 1996, 27: 647 - 651
Indications for Biopsy
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Pretreatment
● Recommended
● Onset age < 6 months
● Macroscopic hematuria
● Microscopic hematuria and HTN
● Low C3
● Renal failure
● Discretionary
● Onset between 6-12 months or > 12 years
● Persistent HTN of hematuria
Indications for Biopsy
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Post treatment
● Steroid resistance
● Frequent relapsers
Minimal change disease
Minimal change disease
Pathogenesis of minimal change disease
circulating permeability factor
(hemopexin?)
1. decreased synthesis of glomerular
polyanions (heparan sulfate) by podocytes
2. impaired adhesion of podocytes to GBM
( -dystroglycan, 1-integrins?)
4. expression of TGF1 detectable almost only
in steroid resistant MCD and FSGS
1.
Minimal change disease
1.
2.
3.
4.
full-blown nephrotic syndrome with
selective proteinuria
hematuria, hypertension and
reduced renal function uncommon
absence of glomerular
abnormalities on LM and IF
fusion of epithelial cells foot
processes on electron microscopy
Minimal change diseaseprevalence among nephrotic patients
Children
Young adults
Adults > 40 years
- 85 – 95%
- 50%
- 20 – 25%
Classification of patients with minimal change
disease based on response to corticosteroids
1.
Steroid responsive (sensitive)
develop complete remission of proteinuria
within 8 – 12 weeks of treatment
(in adults remission should develop within 16
weeks)
2. Steroid dependent
develop relapse during tapering of steroids or
within 2 weeks after cessation of therapy
3. Steroid resistant
fail to respond to steroid treatment at all
Definitions
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Steroid Dependence- Two consecutive
relapses occurring during corticosteroid
treatment or within 14 days of its cessation
➲ Steroid Resistance- Failure to achieve
response in spite of 4 weeks of prednisone
60 mg/m2*day
Clinical course of MCD in children
Remission
- 90%
a. no relapses
b. infrequent relapses
c. frequent relapses and
steroid dependent
- 20%
2. Resistance to steroids
- 10%
1.
a. response to alternative treatment
b. refractory to any kind of treatment
- 40%
- 30%
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2%
In adults, initial response rate is lower, relapses and
steroid dependence are less frequent
8%
Therapy of MCD in children –
current recommendations
Initially course of prednisone 60 mg/m2 for 4-6
weeks with 40 mg/m2 every alternate day for
another 4-6 weeks
2. Relapses treated in a similar way, but tapering
of prednisone starts when urine becomes
protein free
3. Frequent relapsers and steroid dependent
patients treated either by cyclophosphamide
2 mg/kg/day for 8 weeks or by cyclosporine
5 mg/kg/day for 6-12 months
4. Treatment of steroid resistant patients is
usually unsatisfactory
1.
Therapy of MCD –
modifications in adults
Initially course of prednisone 1mg/kg for 8-16
weeks or for one week after remission is
achieved, then several weeks (one month) 1
mg/kg on alternate days, thereafter
corticosteroids are slowly tapered during
several months
2. Relapses treated in a similar way
3. Frequent relapsers and steroid dependent
patients treated either by CPH 2 mg/kg/day for
8 weeks or by CyA 5 mg/kg/day for 6-12
months
4. Treatment of steroid resistant patients is
usually unsatisfactory
1.
Mild FSGS
Moderate FSGS
Tip lesion in early FSGS
Collapsing FSGS
Etiology of FSGS
1.
Primary FSGS
a. glomerular tip lesion
b. collapsing glomerulopathy
2. Secondary FSGS
a. healing focal lesions (FSGN)
b. hyperfiltration in residual nephrons
- agenesis of one kidney
- vesicoureteral reflux
- morbid obesity
c. damage to epithelial cells
- HIV nephropathy
- heroin nephropathy
Classification of FSGS
Genetic FSGS
a. podocin
b. -actinin
2. Immunologic
mechanisms not yet identified
3. Viral FSGS
a. HIV
b. hepatitis C
4. Toxic FSGS
a. heroin
b. pamidronate
1.
Pathogenesis of primary FSGS
1.
Late onset congenital FSGS
deficiency of podocyte proteins
(podocin, -actinin, CD2AP, et al.)
2.
Circulating permeability factors
a. imunoglobulin, or Ig-like molecule
b. protein of MW about 30-50 kDa
c. factor inhibiting inducible NO synthase
mesangial cells (hemopexin)
in
3. Deficient inhibitors of permeability factors lost
in urine
apolipoproteins of HDL complex
(e.g. apo J, apo E2 and apo E4)
Permeability factors in MCD and FSGS
Glassock, J Am Soc Nephrol, 2003, 14: 541 - 543
1.
2.
3.
4.
Permeability factors in MCD and FSGS may be different
Among PF described in MCD (e.g. heparanase, VEGF)
hemopexin is best characterized (Cheung et al., Kidney Int,
2000, 57: 1512 – 1520)
In FSGS 30-50 kD weakly anionic, heat labile, proteasesensitive factor inhibiting NO production in mesangial
cells was identified with the Palb assay (Sharma et al.,
Kidney Int, 2000, 58: 1073 - 1079).
This PF is increased also in pts with genetic mutation of
podocin (Carraro et al., JASN, 2002, 13: 1946 - 1952).
Serial estimates of permeability factors in FSGS
Cattran et al., J Am Soc Nephrol, 2003, 14: 448 - 453
1.
Serum permeability activity assessed in 27 pts with
FSGS treated either by cyclosporine or placebo before
and after 26 weeks of treatment (Cattran et al., Kidney Int.,
1999, 56: 2220 – 2226)
2.
3.
4.
Proteinuria decreased in cyclosporine treated patients
from 7.2 to 3.1 g/day and did not change in pts on
placebo (from 9.5 to 7.4 g/day)
Serum permeability activity changed neither in
cyclosporine (from 0.31 to 0.46), nor in placebo (from
0.41 to 0.36) treated pts
Antiproteinuric effect of cyclosporine seemed to be
independent on changes of Palb
Focal segmental glomerulosclerosis
Asymptomatic proteinuria or full blown
nephrotic syndrome
2. Hypertension, microscopic hematuria
and decreased renal function common
3. Slowly progressive disease
– 50% 10-year renal survival
4. Sclerosis of segments of glomerular tuft
1.
Cumulative renal survival in FSGS
Korbet, NDT, 1999, 14 (Suppl. 3): 68 - 73
Cumulative renal survival in FSGS
Korbet, NDT, 1999, 14 (Suppl. 3): 68 - 73
Treatment of primary FSGS – current
recommendations
1.
2.
3.
Response to corticosteroids may increase from only
10-30% up to 60% with longer treatment with higher
dose (60 mg/m2 at least 3 months, patients should be
considered steroid resistant after 6 months)
Cyclosporine may reduce proteinuria and lower the
risk of progression to ESRD even in steroid resistant
patients, treatment should be long (at least 6 months),
relapses after cyclosporine withdrawal common
Cytotoxics remain only second-line therapy, the
evidence for their effect in steroid resistant patients is
not conclusive
Membranous nephropathy
Membranous nephropathy
Membranous nephropathy
Membranous nephropathy
Secondary
- infections
(hepatitis B, syphilis, malaria)
- drugs
(organic gold, penicillamine,
NSAID)
- neoplasms
(carcinomas, e.g. Colon, lung, or
stomach, and lymphomas)
- systemic lupus erythematosus
2. Idiopathic
1.
Idiopathic
membranous nephropathy
1.
2.
3.
4.
5.
Membranous nephropathy represents 15-25%
of adult nephrotic syndrome
Nephrotic proteinuria is present in about 80%
of patients, remaining patients have
asymptomatic proteinuria
Microscopic hematuria is common
Hypertension and chronic renal failure are
uncommon at presentation, but may develop
during follow-up
Histology – subepithelial deposits along often
thickened GBM
Natural course of idiopathic membranous
nephropathy
1.
2.
3.
Spontaneous remission may develop in
about one third of patients
Nephrotic syndrome persists in another
third of patients
Only 20-30% of patients progress to
ESRD during 20-30 years of follow up
Cyclosporine in steroid-resistant MN
Cattran et al., Kidney Int., 2001, 59: 1484 - 1490
 complete or partial remission developed after 26
weeks in 75% of pts treated by CyA vs. in 22% of pts
treated by placebo
 during 52 weeks relapse developed in 43% of pts
treated by CyA and 40% of pts treated by placebo
 at the end of follow-up in remission was 39% of pts
treated by CyA and 13% of pts treated by placebo
Treatment of idiopathic membranous
nephropathy – current
recommendations
1.
2.
3.
4.
Corticosteroids should not be used a sole
therapy
Azathioprine is not effective in reversing or
stabilizing progressive renal insufficiency
Cytotoxics induce prolonged remission of
nephrotic syndrome and improve renal
survival, their use should be reserved for
patients with progressive disease
Cyclosporine seems to be effective in
progressive renal insufficiency
Guidelines for the treatment of IMN
Cattran, Kidney Int., 2001, 59: 1983 - 1994
Proliferative glomerulonephritides
1.
Microscopic hematuria and/or bouts of
macroscopic hematuria
- mesangial proliferation
(IgA nephropathy)
2. Microscopic hematuria with proteinuria
- mesangial proliferation with peripheral
expansion of mesangium
(membranoproliferative GN)
Ultrastructural changes in glomerular capillaries in mesangioand membranoproliferative GN
IgA nephropathy –
mesangioproliferative glomerulonephritis
IgA nephropathy
Pathogenesis of IgA nephropathy
Gómez-Guerrero et al., Kidney Int, 2002, 62: 715 - 717
1.
2.
3.
4.
Aberrantly O-glycosylated IgA1 with exposed GalNAc
may be recognized as antigens by IgG
Circulating immune complexes of IgA1 and IgG and/or
IgA1 and soluble FcRI (CD89) were identified in pts
with IgA nephropathy
Except from ASGP-R, CD89, Fc/R and TfR mesangial
cells may express further, not yet described IgA
receptors
Patients with IgA nephropathy have increased
expression of megsin (serine protease inhibitor –
serpin). Overexpression of megsin leads to
progressive mesangial matrix expansion
IgA nephropathy
1.
2.
3.
Commonest glomerulonephritis in
Europe (20-40% of primary
glomerulonephritides)
Typical clinical presentation –
asymptomatic microscopic hematuria or
episodes of parainfectious macroscopic
hematuria
Natural history is not benign – at least
20% of patients develop ESRD during 20
years
IgA nephropathy –
negative prognostic factors
a. clinical
hypertension
proteinuria (> 1 g/24 hrs)
decreased renal function at presentation
b. histologic
glomerulosclerosis
interstitial fibrosis
vascular sclerosis
IgA nephropathy - treatment
1.
2.
3.
4.
Strict control of hypertension with ACE
inhibitors
Fish oil in patients with slowly
progressive course of renal insufficiency
Corticosteroids in proteinuric patients
with preserved renal function
Cytotoxics in patients with progressive
renal insufficiency
Corticosteroids in IgA nephropathy:
long-term results
Pozzi et al., J Am Soc Nephrol, 2004, 15: 157 - 163
1.
2.
3.
Secondary analysis of a multicenter,
randomized, controlled trial of 86 adult IgAN
treated for 6 months either with intravenous
methylprednisolone followed by oral steroids
of supportive therapy
Ten-year renal survival was significantly better
in the steroid than in the control group (97%
vs. 53%, p=0.0003)
Proteinuria decreased in patients who did not
double baseline serum creatinine and
increased in progressive patients
Evidence-based recommendations for IST in IgAN: handle with
caution
Floege, Nephrol Dial Transplant, 2003, 18: 241 - 245
1.
2.
3.
In low risk pts with Pu < 1.5 g/day and normal
GFR, steroid therapy may reduce proteinuria,
but its effect on long-term outcome is
uncertain
In pts with Pu 1 – 3.5 g/day and preserved
renal function 6 month steroid course is
indicated
In pts with progressive renal failure as long as
serum creatinine does not exceed 250 mol/l
steroids plus cytotoxics are recommended
Membranoproliferative glomerulonephritis
Membranoproliferative glomerulonephritis
Type I –
a.
Secondary
– infection
(visceral abscesses, endocardisis,
infected ventriculoatrial shunts,
malaria)
- systemic diseases
(type III-IV of lupus nephritis)
- paraproteinemias
( LCDD, cryoglobulinemia)
- thrombotic microangiopathies
( HUS/TTP, APS)
b. Idiopathic
Type II – dense deposit disease
Membranoproliferative glomerulonephritis –
type I
Membranoproliferative glomerulonephritis –
type II (dense deposit disease)
Idiopathic MPGN type I
1.
2.
3.
4.
5.
relatively rare in developed countries
occurs in younger adults
presents with nephrotic syndrome and
microscopic hematuria
slowly progressive disease – 50% 10year renal survival
treatment of nephrotic adults is
controversial (corticosteroids, or
antiplatelet agents?)
MPGN type II
(dense deposit disease)
1.
2.
3.
4.
very rare disease
nephritic factor with
hypocomplementemia
more expressed nephritic features
and more aggressive course
no effective therapy
Therapy of glomerular diseases
1.
Drugs and procedures with relatively well
defined indications
corticosteroids
cytotoxics (CPH, chlorambucil)
cyclosporine
symptomatic treatment
(ACEI, AIIA, and other antihypertensives,
NSAIDS
lipid lowering drugs)
Therapy of glomerular diseases
2. Drugs and procedures with limited experience
and not well defined indications
mycophenolate mofetil
tacrolimus
rapamycin
intravenous immunoglobulins
monoclonal antibodies (e.g. infliximab, rituximab)
soluble cytokine receptors (e.g. etanercept)
plasma exchange
immunoadsorption
Conclusions
Patients suffering from primary GN are
endangered by:
a. complications of nephrotic syndrome
b. progression to ESRF
2. Urinary findings are important, but renal biopsy
remains essential for diagnosis, treatment and
assesment of outcome
3. primary GN are treatable diseases, patients
should be treated according to available
evidence
4. further progress in treatment depends on
better understanding of their pathogenesis
1.