GLOMERULOPATHY

clinical categories

➲ 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

➲ 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

➲ 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

➲ Immunologic reactions
➲ Vascular diseases
➲ Abnormalities in coagulation
➲ Metabolic defects
➲ Hereditary factors
➲ Unknown factors
 GLOMERULOPATHY
immunologic mechanism

➲ Circulating immune complex – mediated

disease
➲ Antitissue antibody – mediated disease
➲ Cell- mediated disease
➲ Disease associated with activation of
alternative complement pathway
 Physiology of protein excretion

➲ Proteinfiltration through the glomerulus is

dependent on the protein size, shape and
electrical charge
Physiology of protein excretion

➲ Protein charge

● Atphysiological pH, most proteins are

negatively charged

● Since the basement membranes are also

negatively charged, most proteins are
retained
Physiology of protein excretion

➲ Protein size

● Proteinsgreater than 40kDa are almost

completely retained

● Thus, only small proteins, e.g. retinol-

binding protein, ß2 microglobulin, passes
into the ultrafiltrate
Physiology of protein excretion

➲ However, most of the filtered proteins are

reabsorbed by the proximal tubules.

➲ Consequently, very little plasma protein

appears in the urine

➲ Normally < 150mg/24hours

 “Physiological” proteinuria

➲ In some non-pathological situations, a higher

than normal urine protein level is found:
● A concentrated spot urine
● Exercise
● Orthostatic proteinuria
● Contamination e.g. from vagina
 Classification

➲ Tubular proteinuria
● Tubular dysfunction
● Overflow proteinuria

➲ Glomerular proteinuria
● Selective proteinuria
● Non-selective proteinuria
● microalbuminuria
 Tubular proteinuria

➲ Thisoccurs when glomerular function is

intact, but protein is lost to the urine either
because of:

● Tubular dysfunction
● Overflow
 Tubular proteinuria

➲ 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: retinol-
binding protein, ß2 microglobulin, lysozyme,
light chains, haemoglobin, myoglobin
 Tubular proteinuria

➲ Tubular dysfunction
● Pyelonephritis
● Acute tubular necrosis
● Papillary necrosis e.g. analgesic
nephropathy
● Heavy metal poisoning
● SLE
● Fanconi’s syndrome
 Tubular proteinuria

➲ Overflow proteinuria

● Occurs when the concentration of one of

the small MW proteins is so high that the
filtered load exceeds the tubular
reabsorptive capacity

● Thus, the excess filtered load appears in

the urine
 Tubular proteinuria

➲ Overflow proteinuria

● Bence Jones proteinuria

● Myoglobinuria
● Haemoglobinuria
 Glomerular proteinuria

➲ When there is glomerular dysfunction,

proteins > 40kDa can escape into the urine

➲ The most common form of proteinuria

 Glomerular proteinuria

➲ Causes
● Glomerulonephritis
● Diabetes mellitus
● Multiple myeloma
● Amyloidosis
● SLE
● Pre-eclampsia
● Penicillamine, gold
 Definitions

➲ 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
 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

➲ 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 in
33% of patients
 NS laboratory- Plasma Protein

➲ Albumin
● Hypoalbuminemia due to loss via the kidney
● Urinary excretion
● Proximal tubular cells catabolism

➲ Immunoglobulins
● IgG levels reduced
● IgM levels elevated
● IgM-IgG-Switching
 NS laboratory- Hyperlipidemia

➲ Increased synthesis of cholesterol,

triglycerides and lipoproteins
➲ Decreased catabolism of lipoproteins
● 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 tissue diseases
 HIV/AIDS
 nephrotoxins
 nsaids
 mercury poisoning
 penicillamine
 gold salts
Other causes of the nephrotic syndrome 2

 Allergies
 bee sting
 pollens
 poison ivy
 Circulatory effects
 congestive cardiac failure
 constrictive pericarditis
 renal vein thrombosis (cause or result?)
 Neoplastic
 leukaemia
 solid tumours
NS epidemiology
 NS treatment- Diet

➲ 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

➲ Controversial
➲ Indication- Hypovolemia
● Abdominal pain
● Hypotension
● Oliguria
● Renal insufficiency
 NS complications

➲ Mortality
● 1940’s- 40% 1 year mortality
● Now 1-2%
● Main cause of death
●Infection
●Thrombosis
Corticosteroids Initiation in NS

➲ 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
➲ Cushingoid habitus
➲ Obesity
➲ Striae
➲ Hirsutism
➲ Acne
➲ Growth failure
➲ Avascular necrosis
➲ Osteoporosis
 Steroid Toxicity

➲ Peptic ulceration
➲ Pancreatitis
➲ Posterior lens opacities
➲ Myopathy
➲ Increased ICP
➲ Susceptibility to infection
Options for Alternative Therapy
in NS
➲ Alkylating Agents
● Nitrogen mustard
● Cyclophosphamide
● Chlorambucil
➲ Levamisole
➲ Cyclosporine
Indications for Alternative Therapy
in NS
➲ 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 peri-
orbital- 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

➲ 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 encephalopathy (seizures, coma)

 Heart Failure (pulmonary oedema)

 Uraemia requiring dialysis

 Acute poststreptococcal GN

➲ 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

➲ 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

➲ 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

1. 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
 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

➲ 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

➲ Post treatment
● Steroid resistance
● Frequent relapsers
Minimal change disease
Minimal change disease
 Pathogenesis of minimal change disease

1. 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
 Minimal change disease

1. full-blown nephrotic syndrome with

selective proteinuria
2. hematuria, hypertension and
reduced renal function uncommon
3. absence of glomerular
abnormalities on LM and IF
4. fusion of epithelial cells foot
processes on electron microscopy
 Minimal change disease-
prevalence among nephrotic patients

Children - 85 – 95%
Young adults - 50%
Adults > 40 years - 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

➲ 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

1. Remission - 90%
a. no relapses - 20%
b. infrequent relapses - 40%
c. frequent relapses and
steroid dependent - 30%
2. Resistance to steroids - 10%
a. response to alternative treatment - 8%
b. refractory to any kind of treatment - 2%

In adults, initial response rate is lower, relapses and

steroid dependence are less frequent
 Therapy of MCD in children –
current recommendations
1. 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
 Therapy of MCD –
modifications in adults
1. 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
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
1. 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
 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 in
mesangial cells (hemopexin)
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. Permeability factors in MCD and FSGS may be different

2. Among PF described in MCD (e.g. heparanase, VEGF)
hemopexin is best characterized (Cheung et al., Kidney Int,
2000, 57: 1512 – 1520)
3. In FSGS 30-50 kD weakly anionic, heat labile, protease-
sensitive factor inhibiting NO production in mesangial
cells was identified with the Palb assay (Sharma et al.,
Kidney Int, 2000, 58: 1073 - 1079).
4. 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. 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)
3. Serum permeability activity changed neither in
cyclosporine (from 0.31 to 0.46), nor in placebo (from
0.41 to 0.36) treated pts
4. Antiproteinuric effect of cyclosporine seemed to be
independent on changes of Palb
 Focal segmental glomerulosclerosis

1. 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
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. 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)
2. 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
3. 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
1. 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
 Idiopathic
membranous nephropathy
1. Membranous nephropathy represents 15-25%
of adult nephrotic syndrome
2. Nephrotic proteinuria is present in about 80%
of patients, remaining patients have
asymptomatic proteinuria
3. Microscopic hematuria is common
4. Hypertension and chronic renal failure are
uncommon at presentation, but may develop
during follow-up
5. Histology – subepithelial deposits along often
thickened GBM
Natural course of idiopathic membranous
nephropathy

1. Spontaneous remission may develop in

about one third of patients
2. Nephrotic syndrome persists in another
third of patients
3. 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. Corticosteroids should not be used a sole
therapy
2. Azathioprine is not effective in reversing or
stabilizing progressive renal insufficiency
3. Cytotoxics induce prolonged remission of
nephrotic syndrome and improve renal
survival, their use should be reserved for
patients with progressive disease
4. 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 mesangio-
and membranoproliferative GN
 IgA nephropathy –
mesangioproliferative glomerulonephritis
IgA nephropathy
 Pathogenesis of IgA nephropathy
Gómez-Guerrero et al., Kidney Int, 2002, 62: 715 - 717

1. Aberrantly O-glycosylated IgA1 with exposed GalNAc

may be recognized as antigens by IgG
2. Circulating immune complexes of IgA1 and IgG and/or
IgA1 and soluble FcRI (CD89) were identified in pts
with IgA nephropathy
3. Except from ASGP-R, CD89, Fc/R and TfR
mesangial cells may express further, not yet described
IgA receptors
4. 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. Commonest glomerulonephritis in
Europe (20-40% of primary
glomerulonephritides)
2. Typical clinical presentation –
asymptomatic microscopic hematuria or
episodes of parainfectious macroscopic
hematuria
3. 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. Strict control of hypertension with ACE
inhibitors
2. Fish oil in patients with slowly
progressive course of renal insufficiency
3. Corticosteroids in proteinuric patients
with preserved renal function
4. 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. 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
2. Ten-year renal survival was significantly better
in the steroid than in the control group (97%
vs. 53%, p=0.0003)
3. 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. 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
2. In pts with Pu 1 – 3.5 g/day and preserved
renal function 6 month steroid course is
indicated
3. 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. relatively rare in developed countries
2. occurs in younger adults
3. presents with nephrotic syndrome and
microscopic hematuria
4. slowly progressive disease – 50% 10-
year renal survival
5. treatment of nephrotic adults is
controversial (corticosteroids, or
antiplatelet agents?)
 MPGN type II
(dense deposit disease)

1. very rare disease

2. nephritic factor with
hypocomplementemia
3. more expressed nephritic features
and more aggressive course
4. 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
1. 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