IgA Nephropathy

IgA Nephropathy

1. Pathogenesis

   • Defect in IgA1 glycosylation(?inherited or acquired)
     • High levels of circulating defective IgA
       • Mucosal infection
         • Generation of IgG targeted to defective IgA (?via molecular mimicry)
           • IgA/IgG immune complex formation and deposition in glomerular mesangium
         • Often URTI
           • Bacterial
             • Mycoplasma, Haemophillus, campylobacter,Yersinia
             • Staph
               • Often leads to RPGN
           • Viral
             • Adenovirus, EBV, CMV

2. Presentation

   • Variable!
     • Macroscopic haematuria
       • 50% of cases
       • Episodes of brown coloured haematuria, clots ususual
       • Haematuria often onset 24 hours after URTI (as opposed to the 3 weeks of post-strep GN)
       • Often associated with loin pain due to renal capsular stretch form kidney swelling
     • Asymtomatic Microscopic haematuria with non-nephrotic proteinuria
       • 30% of cases
     • Nephrotic syndrome
       • Rare presentation, 5% of cases
     • AKI
       • Rare presentation, signifies RPGN/Cresentic transformation
     • CKD
       • Especially in the elderly
     • Classic presentation: 20-30 yo male with macroscopic haematuria and an URTI
     • Presentation as a part of HSP

3. Pathology

   • H+E
     • Mesangial proliferation
     • Occasionally with FSGS in severe cases
     • Tubulointerstitial fibrosis indicates chronicity (as in all GNs)
   • IF
     • Diffuse mesangial IgA staining
     • C3 staining in 90%
     • IgG, IgM in 40%
   • EM
     • Dense deposits in mesangium
   • Note this appearance very similar to SLE nephritis
     • Differential clues
       • Classical presentation
       • Serum IgA often high in IgAN
       • C3,C4 normal in IgAN, abnormal in SLE

4. Treatment

   • Depends upon presentation and biopsy findings
   • Macroscopic haematuria with preserved renal F'n
     • Aggressive hydration to flush out tubular casts
   • Macroscopic haematuria with AKI
     • Mandates renal biopsy
       • ATN only
         • Nil Rx
       • Glomerular findings
         • Induction: Prednisone 05-1mg/kg OD and cyclophos 2mg/kg OD for 8/52
         • Maintainence: Weaning prednisone plus AZT 2.5mg/kg daily
   • Nephrotic synd
     • 0.5-1mg/kg daily Prednisone for 8/52 then taper
     • Nephrotic synd supportive measures
       • Breakdown of Glomerular Disease
   • Non-nephrotic proteinuria
     • ACE/ARB

5. Progression/Prognosis

   • 30% clinical remission (mildest cases)
   • Otherwise progressive disease
   • Poor prognostic factors
     • Disease severity at presentaion
       • Hypertension
       • Proteinuria
       • Kidney excretory function
     • biopsy findings of chronicity
       • Tubulointerstitial fibrosis
     • Obesity
     • Hyperuricaemia

6. transplant recurrence if IgAN

   • 60% of grafts
   • Increases linearly with age of graft, approx. 30% at 10 years