Primary glomerulonephritides (GN) II Proliferative GN by 1rgrJJJ


									Primary glomerulonephritides (GN)
       II Proliferative GN

             Miroslav Merta
      Klinika nefrologie 1. LF a VFN
            Proliferative versus neproliferative GN
    (glomerular capillary loop – ultrastructural changes)

                           Urinary                                                         Subendothelial
Epitheliál                 space           Acute GN                                        deposits
                          membran         Increased number and
                          e               proliferation of             neutrophils
                    Capillar              mesangial cells
                    y lumen
                                     Proliferative GN                                   Subepithelial deposits
Mesangial                                                                            Subendothelial deposits
cells                                                            Increaed
                                                                 number and
                                                                 proliferation of
    Normal glomerulus                                            mesangial cells
                                                                 to distal parts
         Increased number and                                    of capillary loop      neutrophils
         proliferation of
         mesangial cells
     mesangial deposits of IgA
                                     Mesangioproliferative               Membranoproliferative
                                     GN                                  GN
Dysmorphic erythrocytes (of glomerular origine)
    are typical finding in proliferative GN

Urine sediment in phase   Electroscanning microscopy
                       Acute (postreptococal) GN



Increased number and

                                            Subepithelial (hump-like)
                  Acute (postreptococal) GN

Light microscopy (LM): picture of diffuse proliferative
GN with prominent influx of neutrophils and event. Other
cells, (= exsudative GN)
                                                              Imunofluorescence (IF): coarsely diffusely
                                                              lightening of C3, event. IgG, rarely other
                                                              Three charakteristic types:
                                                               1) mesangial
                                                              2) „star sky
                                                              3) „girlands (associated with nephrotic
                                                       Elektrone microscopy (EM): proof of
                                                       deposits subendothelially and
                                                       condensation of cytoskeleton in
                                                       adjacent epithelial cytoplasma. N =
            Akutní (postreptokoková GN)
                     - basic characteristics
1.   Its frequency is decreasing in Europe, m:f 2:1, common in children.
2.   Acute GN is caused by „nefritogennic“ strains of STREP. pyogenes
     (infections of higher respiratory airways, event. cutaneous infections).
     Infection precedes PSGN for several weeks.
3.   Patogenesis: antigens of STREP (např. GADH)  activation of
     complement  development of circulatory immuno complexes (event.
     Their deposition), persistation of STREP infection
4.   Clinical picture: acute nephritic syndrome. Always present hematuria,
     often swlling (90%), hypertension (80%), proteinuria (in 30% NS),  GFR
5.   Laboratory findings: findings reflecting presence of STREP infection
     titers of ASO (2x ), positivity of STREPTOZYME panel (involving
     antibodies against 4 STREP antigenes). Transitory  C3 (in 90%), event.
6.   Histological picture: difuse endocapillary GN with proliferation of
     mesangium and endothel, typically exsudation (leukocytes). Rarely
     complicated by RPGN, cryoglobulinemia and s.o.)
            Acute (postreptococal GN)
          – diagnosis, treatment, prognosis
1.  Renal biopsy not routinely warranted; RB indicated: atypical
    course (NS), long-term  C3, important  GFR
2. Treatment involves: treatment of persistating STREP
    infection and treatment of nefritic syndrome:
   • Treatme of persistating STREP infection: PNC 1.2 M u./7-
       10 days
   • Treatment of nephritic syndrome: restriction of fluids and
       NaCl, diuretics, rarely hemodialysis (in 20-30% adults)
   • If complicated by RPGN - corticosteroids, (CPA?)
3. Prognosis: clinical manifestation is short (2 weeks), healing
    during weeks, mild proteinuria (< 0.5g/l) may persist for
    weeks and hematuriea even for 1 year. Long-term prognosis
                IgA nephropathy – IGAN
         mesangioproliferative glomerulonephritis

     Increaing number and
     proliferation of
     mesangial cells

Mesangial deposits of
IgA, rarely IgA in capilars
(serious forms)
                     IGAN- histological findings

Light microscopy (LM): Focal (here) or diffuse mesangial             Immunofluorescence (IF): diffuse mesangial
proliferation. Rarely picture of crescentic GN, more frequently      deposits of IgA, co-localisation of other Ig less
picture of sclerotisating GN. Vasculitic lesions occur in HSP.       intensive

                                                                  Electrone microscopy (EM):
                                                                  demonstation of deposits in
  Patogenesis of IgA nephropathy
Gómez-Guerrero et al., Kidney Int, 2002, 62: 715 - 717

   Impairment of O-glycosylation of IgA1
   causes, that exposed domain GalNAc is
   recognized as antigennic
           IgA nephropathy
          - basic characteristics
1. Commonest GN in Europe (20-40% of all
   primary GN)
2. Typical clinical picture – asymptomatic
   microskopic hematuria či episodes of
   parainfectious macroskopic hematuria
3. Natural course of the disease is not benign – at
   least in 20% patients ESRD develops within
   20 years
4. Histology – mesangial deposits of IgA
   demonstrated by IF
            Prognosis of IgAN
       – negative prognostic factors
a. klinical
     proteinuria (> 1 g/24 h)
     decrease of GFR at the time of diagnosis

b. histological
    interstitial fibrosis
    vascular sclerosis
                   Prognosis of IGAN
- dependance on renal function and proteinuria at the
                  time of diagnosis
        Dependance on renal            Dependance on
        function (creatininemia)       protenuria

  Radford et al., J Am Soc Nephrol, 1997, 8: 199 - 207
            IgAN - treatment
1. Strict control of hypertension achieved
   preferentially with ACE inhibitors (event. ABR)
2. Fish oil (unsaturated alpha omega acids) in
   patients with slow progression of renal
   insufficiency (weak effect)
3. Cortikosteroids in patients with proteinuria,
   which do have preserved renal functions
4. Cytotoxic agents in patients s progressing renal
        Membranoproliferative glomerulonephritis
                     – type I a II
Subendothelal deposits                                 Mesangial sferic
                                 New formation
                                 of BM

     number of
     mesangial cells
     and their
     proliferation to                                                         neutrophils
     distal parts of                             Increasing
     capillary loop                              number of
                         neutrophils             mesangial cells
                                                 and their
                                                 proliferation to
                                                 distal parts of
                                                 capillary loop

                                                         Intramembranus dense deposits

                MPGN type I                                         MPGN type II
          Membranoproliferative GN type I

 Light microscopy (LM): hypercelullarity and                Immunofluorescence (IF): diffuse periferal
 proliferation,, lobular appearance, double contour of BM   granular deposits of IgG, event.IgM, and C3 (in type
 (tram track) – as consequence of interposition of          II only C3)

Electrone microscopy (EM): demonstration of deposits         Electrone microscopy (EM): dense material
subendothelially and a mesangially, double contour of BM,    substitutes BM
         Membranoproliferatie GN (MPGN)
Type I
   a. Idiopatic
   b. Secondary
    – infection
               (visceral abscesses, endocarditis,
       infection of atrioventricular shunts, malaria)
   - systemic diseases
               ( SLE – LN type III-IV)
   - paraproteinemias
               ( LCDD, cryoglobulinemia)
   - thrombotic microangiopathy
               ( HUS/TTP, APS)
Type II – disease of dense deposits
          Idiopatic MPGN type I
           - basic characteristics
1. Relatively rare disease in developed countries
2. It is found in less aged subjects
3. Clinical findings at the time of dg: usually NS
   and microskopic hematuria
4. Slowly progressing disease – during 10-y
   interval 50% patients do progress into ESRD
5. Treatment in adults is controversial
   (corticosteroids, CPA, anticoagulation)
Membranoproliferative GN type II

  Electrone microscopy (EM): dense material substitutes BM
        Idiopatic MPGN type II
         - basic characteristics

1. Very rare disease
2. Clinically: presence of nephritic factor with
3. More pronounced nephritic features and
   more agressive course of diasease
4. Efficient treatment unknown

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