Transcript 投影片 1

Intern Seminar :
IgA Nephropathy
Teacher : 邱元佑醫師
Presentation : 陳沛吟
Brief history：
• 17-year-old, Boy
• 民國85/4 (10 y/o)：proteinuria was found
incidentally in school health examination
Persistent proteinuria
86/11：renal biopsy：IgA nephropathy
• Lab：IgG:576↓, IgA:142, IgE:<28.3
C3:111, C4:27.8
BUN:13, Crea:0.6, albumin:3.9
DPL:1911 mg/day
Brief history
Persistent
proteinuria
Proteinuria
85/4
(10 y/o)
Biopsy：
IgAN
86/11
Heavy proteinuria
+ echo：
parenchymal dz.
2nd Biopsy：
FSGS & TIN
OPD F/U
92/1
1. Captopril→Losartan
2. 89/4 ~ 92/1
Predinisolone + Solumedrol
Proteinuria：150~500 mg/dL
BUN/Cr:
134/15.4
H/D
CAPD
92/9
92/10
(17 y/o)
BUN / Creatinine：
140
130
120
110
100
90
80
70
60
50
40
30
20
10
0
136
BUN
Crea
18.8
16
1.2
92
92
92
92
92
.9
.8
.7
.6
.1
.1
.5
91
91
91
90
2
1
BP：100/70
118/84
138/94
142/98
Discussion:
IgA Nephropathy
Definition:
Only by biopsy：IgA immunocomplex
deposits in the glomerular mesangium
• Mesangial electron dense deposits with
↑mesangial matrix & cellularity in IgAN
Incidence：
• Japan, France, Australia：18~40% of
all primary glomerular diseases
United States, Canada：only 2~10%
• male > female
• Occur at all ages
• predominate：older children and young
adults, 20+~30+ y/o：↑
Causes:
• IgAN：Primary (idiopathic)
or secondary
• Cause of primary IgAN：unknown
Genetic factors：
• Familial clustering：familial predisposition
is a very common finding (9.6% of IgAN
pt’s siblings have GN)
• ACE gene polymorphism (DD genotype)：
correlated to the pathological severity and
course of IgAN.
• HLA genes：class Ⅱ products – DP, DQ,
and DR：susceptibility to IgAN.
Genetic factors：
• Platelet-activating factor (PAF)
acetylhydrolase gene mutation：degree
of proteinuria and the extent of
mesangial cell proliferation.
• IgA immune system：IgA1 synthesis
• Complement factors：homozygous null
C4 phenotype↑, C3FF homozygous
phenotype↑
(Pediatric Nephrology 2001, 16:446-457)
Causes of Secondary IgAN
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Infection：HIV, leprosy
Neoplasia：ca. of the lung, pancreas
Liver diseases：Hepatitis B, cirrhosis,
Skin diseases： Psoriasis
Lung diseases：sarcoidosis
Systemic immunological disorders：
SLE, RA, AS, Reiter’s syndrome……
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
IgAN In Children：
• > 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
IgAN In Children：
• Gross hematuria often in association
with URI.
• Proteinuria：often, but severity < nephrotic
• Hypertension：mild to moderate
• Serum IgA level：8~16%↑in children
(30~50%↑ in adults)
※ no diagnostic value
Differential Diagnosis：
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•
Henoch-Schönlein purpura (HSP)
HSP：clinical syndrome
Same：histopathological alterations
Difference：HSP has systemic
symptoms：purpuric rash, arthralgias,
abdominal pain, acute onset, self-limited.
• Variants of the same pathophysiologic
process
Outcome：
• Used to be thought：benign
• Highly variable range of prognosis ：
~ spontaneous remission
~ impaired renal function
~ ESRD
• 20~30%, 15~20 years  ESRD
Pool prognostic Factors：
• Clinical presentation：
1. Persistent hypertension
2. ↑Serum cr., ↓renal function when onset
3. Prolonged or heavy proteinuria (>1g/day)
• Pathological expression：
1. Diffuse mesangial proliferation
2. Extensive glomerular crescents
3. Glomerulosclerosis and tubulointerstitial
change
Treatment
Treatment:
• Goal:
prevent progression of disease and protect
renal function
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ACE Inhibitors
Corticosteroids
Immunosuppressants
Fish-oil supplement
Tonsillectomy
Corticosteroid：
• Corticosteroid：antiinflammatory
& immunosuppressive
• Floege et al：for proteinuria <1.5g/day and
normal GFR：can↓proteinuria
• High risk or renal function worsen：
steroid + cyclophosphamide/cytotoxic
• No effect on renal function was observed
• On-going：corticoteroid + azathioprine
Renin-Angiotensin System
Angiotensinogen
Inactive
peptides
Renin
AngiotensinⅠ
ACE
Angiotensin II
AngiotensinⅡ
Bradykinin
ATI Receptor
AⅡ
Receptor
Endothelium
O 2-
ACEI & AngiotensinⅡ
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,↓proteinuria：proven
ACE inhibitor：
P < 0.05
• Probability of renal survival (<50% increase of baseline serum
creatinine) in enalapril-treated group and control group.
(Roland et al)
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 studies：benefits on renal function
＊ 2 studies：no difference
Fish Oil Supplements：
• Danadio et al：in persistent proteinuria
(>1g/day) & SCr <3 mg/dL ：
↓82% risk in SCr↑ and ↓67% risk of
death or ESRD.
• High-dose: 3.76g EPA+2.94g DHA (8#) v.s.
Low-dose: 1.88g EPA+1.47g DHA (4#)：
no difference
Fish Oil Supplements：
Tonsillectomy：
• IgA：mucosa defense
• Popular in Japan and France.
• Indication：chronic infections
(dental abscess, sinusitis)
• In pediatric：tonsillectomy：↓ gross
hematuria episodes.
• No evidence for affect the progression to CRI
or ESRD.
• Recommended：controversial
Renal Transplantation：
• When ESRD: It is best to transplantation
• In U.S.：IgAN -- 10% of primary GN with
renal transplantation
• Survival：excellent
• Recurrence：20~60% in 5 years
• Equal rates over cadaveric, living, or
related donor.
Conclusion：
• In low risk (proteinuria < 1.5g/day)
1. Steroid for ↓proteinuria (grade B)
2. ACEI (grade C)
• In higher risk：
immunosuppressive therapy (grade A)
 proteinuria 1~3.5g/day steroid x 6 months
 progressive renal failure：
steroid + cytotoxic treatment
About This Case：
• No gross hematuria
• Serum IgA level：normal
• Poor predictors：persistent heavy
proteinuria, hypertension
• Onset~ESRD：only 7 years
Poor drug compliance?
Unknown herbs?
Hypertension?
Summary：
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Primary IgAN：the most common primary GN
Diagnosis：biopsy：IgA deposition
Prognosis：variable, 20~30%ESRD
Treatment：Immunosuppressive therapy
(steroid/ cyclophophamide/ AZT)
ACEI
Fish-oil
Tonsillectomy
Renal transplantation
References:
• JV Donadio, IgA Nephropathy. N Engl J Med
2003;347(10):738-48.
• Yoshikawa N. Tanaka R. Iijima K. Pathophysiology
and treatment of IgA nephropathy in children. Pediatr
Nephrol 2001;16(5):446-57.
• Wyatt RJ. Hogg RJ. Evidence-based assessment of
treatment options for children with IgA nephropathies.
Pediatr Nephrol 2001;16(2):156-67.
• D'Amico G. Natural history of idiopathic IgA
nephropathy: role of clinical and histological
prognostic factors. Am J Kidney Dis 2000;36(2):22737.
References:
• Donadio JV Jr. Use of fish oil to treat patients
with immunoglobulin A nephropathy. Am J
Clin Nutr 2000;71(1 Suppl):373S-5S.
• Julian BA. Treatment of IgA nephropathy.
Semin Nephrol 2000;20(3):277-85.
• Jurgen Floege. Evidence-based
recommendations for immunosuppression in
IgA nephropathy: handle with caution.
Nephrol Dial Transplantation 2003;18:241-5.
• Testbook of Pediatrics, Nelson 17th Edition