Intern Seminar : IgA Nephropathy

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Intern Seminar IgA Nephropathy

• Teacher ?????
• Presentation ???

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Brief history

• 17-year-old, Boy
• ??85/4 (10 y/o)proteinuria was found
  incidentally in school health examination
• ?Persistent proteinuria
• ?86/11renal biopsyIgA nephropathy
• LabIgG576?, IgA142, IgElt28.3
• C3111, C427.8
• BUN13, Crea0.6, albumin3.9
• DPL1911 mg/day

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Brief history
Heavy proteinuria echo parenchymal dz.

Persistent proteinuria
BUN/Cr 134/15.4
2nd Biopsy FSGS TIN
Biopsy IgAN
Proteinuria
CAPD
H/D
OPD F/U
85/4 (10 y/o)
86/11
92/1
92/10
92/9 (17 y/o)
1. Captopril?Losartan 2. 89/4 92/1
Predinisolone Solumedrol Proteinuria150500
mg/dL
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BUN / Creatinine
136
18.8
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1.2

• BP100/70 118/84 138/94 142/98
  

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• Discussion
• IgA Nephropathy

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Definition

• Only by biopsyIgA immunocomplex deposits in
  the glomerular mesangium

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• Mesangial electron dense deposits with
• ?mesangial matrix cellularity in IgAN

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Incidence

• Japan, France, Australia1840 of all primary
  glomerular diseases
• United States, Canadaonly 210
• male gt female
• Occur at all ages
• predominateolder children and young adults,
  2030 y/o?

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Causes

• IgANPrimary (idiopathic)
• or secondary
• Cause of primary IgANunknown

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Genetic factors

• Familial clusteringfamilial predisposition is a
  very common finding (9.6 of IgAN pts siblings
  have GN)
• ACE gene polymorphism (DD genotype)correlated to
  the pathological severity and course of IgAN.
• HLA genesclass ? products DP, DQ, and
  DRsusceptibility to IgAN.

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Genetic factors

• Platelet-activating factor (PAF) acetylhydrolase
  gene mutationdegree of proteinuria and the
  extent of mesangial cell proliferation.
• IgA immune systemIgA1 synthesis
• Complement factorshomozygous null C4 phenotype?,
  C3FF homozygous phenotype?
• (Pediatric Nephrology 2001, 16446-457)

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Causes of Secondary IgAN

• InfectionHIV, leprosy
• Neoplasiaca. of the lung, pancreas
• Liver diseasesHepatitis B, cirrhosis,
• Skin diseases Psoriasis
• Lung diseasessarcoidosis
• Systemic immunological disordersSLE, RA, AS,
  Reiters syndrome

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Five Clinical syndromes

• 1. Gross hematuria (U.S.)
• 2. Asymptomatic microscopic hematuria
• with/without proteinuria----62
• (Japan, Asia)
• 3. Acute nephritis with hypertension
• and/or renal insufficiency
• 4. Nephrotic syndrome
• 5. A mixed nephritic-nephrotic syndrome

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IgAN In Children

• gt 80 children have experience of
• gross hematuria (in U.S.)
• Recurrent gross hematuria is traditionally
  regarded as the hallmark of childhood IgAN.
• Gross hematuria as initial feature ¼
• (asymptomatic child found in school
• screening)
• Gross hematuria is fewer in adults

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IgAN In Children

• Gross hematuria often in association
• with URI.
• Proteinuriaoften, but severity lt nephrotic
• Hypertensionmild to moderate
• Serum IgA level816?in children
• (3050? in
  adults)
• ? no diagnostic value

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Differential Diagnosis

• Henoch-Schönlein purpura (HSP)
• HSPclinical syndrome
• Samehistopathological alterations
• DifferenceHSP has systemic symptomspurpuric
  rash, arthralgias, abdominal pain, acute onset,
  self-limited.
• Variants of the same pathophysiologic process

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Outcome

• Used to be thoughtbenign
• Highly variable range of prognosis
• spontaneous remission
• impaired renal function
• ESRD
• 2030, 1520 years ? ESRD

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Pool prognostic Factors

• Clinical presentation
• 1. Persistent hypertension
• 2. ?Serum cr., ?renal function when onset
• 3. Prolonged or heavy proteinuria (gt1g/day)
• Pathological expression
• 1. Diffuse mesangial proliferation
• 2. Extensive glomerular crescents
• 3. Glomerulosclerosis and tubulointerstitial
  
• change

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• Treatment

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Treatment

• Goal
• prevent progression of disease and protect
  renal function
• ACE Inhibitors
• Corticosteroids
• Immunosuppressants
• Fish-oil supplement
• Tonsillectomy

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Corticosteroid

• Corticosteroidantiinflammatory
• immunosuppressive
• Floege et alfor proteinuria lt1.5g/day and normal
  GFRcan?proteinuria
• High risk or renal function worsen
• steroid cyclophosphamide/cytotoxic
• No effect on renal function was observed
• On-goingcorticoteroid azathioprine

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Renin-Angiotensin System
Angiotensinogen
Renin
Inactive peptides
Angiotensin?
ACE
Angiotensin II
Bradykinin
ATI Receptor
Endothelium
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ACEI Angiotensin?Receptor Blocker

• Angiotensin is a central factor in the
  progression of glomerular sclerosis.
• hypothesis?BP has protective renal effects in
  cases of mild insufficiency with hypertension in
  IgAN.
• ACEI for preserve renal function?
• But,?BP,?proteinuriaproven

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ACE inhibitor
P lt 0.05

• Probability of renal survival (lt50 increase of
  baseline serum creatinine) in enalapril-treated
  group and control group.
  (Roland et al)

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Fish Oil Supplements

• n-3 polyunsaturated fatty acids
• (DHA, EPA)
• Depress eicosanoid and cytokine production
• ? may ?renal inflammation and
  glomerulosclerosis
• ? may prevent renal injury
• Review
• 2 studiesbenefits on renal function
• 2 studiesno difference

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Fish Oil Supplements

• Danadio et alin persistent proteinuria
• (gt1g/day) SCr lt3 mg/dL
• ?82 risk in SCr? and ?67 risk of
• death or ESRD.
• High-dose 3.76g EPA2.94g DHA (8) v.s.
• Low-dose 1.88g EPA1.47g DHA (4)
• no difference

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Fish Oil Supplements
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Tonsillectomy

• IgAmucosa defense
• Popular in Japan and France.
• Indicationchronic infections
• (dental abscess, sinusitis)
• In pediatrictonsillectomy? gross hematuria
  episodes.
• No evidence for affect the progression to CRI or
  ESRD.
• Recommendedcontroversial

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Renal Transplantation

• When ESRD It is best to transplantation
• In U.S.IgAN -- 10 of primary GN with renal
  transplantation
• Survivalexcellent
• Recurrence2060 in 5 years
• Equal rates over cadaveric, living, or related
  donor.

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Conclusion

• In low risk (proteinuria lt 1.5g/day)
• ?1. Steroid for ?proteinuria (grade B)
• 2. ACEI (grade C)
• In higher risk
• immunosuppressive therapy (grade A)
• ? proteinuria 13.5g/day steroid x 6 months
• ? progressive renal failure
• steroid cytotoxic treatment

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About This Case

• No gross hematuria
• Serum IgA levelnormal
• Poor predictorspersistent heavy proteinuria,
  hypertension
• OnsetESRDonly 7 years
• Poor drug compliance?
• Unknown herbs?
• Hypertension?

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Summary

• Primary IgANthe most common primary GN
• DiagnosisbiopsyIgA deposition
• Prognosisvariable, 2030?ESRD
• TreatmentImmunosuppressive therapy
• (steroid/ cyclophophamide/
  AZT)
• ACEI
• Fish-oil
• Tonsillectomy
• Renal transplantation

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References

• JV Donadio, IgA Nephropathy. N Engl J Med
  2003347(10)738-48.
• Yoshikawa N. Tanaka R. Iijima K. Pathophysiology
  and treatment of IgA nephropathy in children.
  Pediatr Nephrol 200116(5)446-57.
• Wyatt RJ. Hogg RJ. Evidence-based assessment of
  treatment options for children with IgA
  nephropathies. Pediatr Nephrol 200116(2)156-67.
• D'Amico G. Natural history of idiopathic IgA
  nephropathy role of clinical and histological
  prognostic factors. Am J Kidney Dis
  200036(2)227-37.

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References

• Donadio JV Jr. Use of fish oil to treat patients
  with immunoglobulin A nephropathy. Am J Clin Nutr
  200071(1 Suppl)373S-5S.
• Julian BA. Treatment of IgA nephropathy. Semin
  Nephrol 200020(3)277-85.
• Jurgen Floege. Evidence-based recommendations for
  immunosuppression in IgA nephropathy handle with
  caution. Nephrol Dial Transplantation
  200318241-5.
• Testbook of Pediatrics, Nelson 17th Edition