4. both NAPlr60 and SPEB61 is widely recog- alone is uncertain, and only 10 to 20% of
nized. Similar properties are present in the patients who present with a sore
streptokinase and enolase, and the nephri- throat in general clinical practice have a
togenic potential of the latter is based on its positive culture for group A Streptococ-
糸球体腎炎を来すAntigens
plasmin-binding properties.74 Recent in- cus.75 Because clinical judgment may
vestigations by Oda and co-workers (Na- miss half of the streptococcal pharyngitis
tional Defense Medical College, Saitama, and wrongly identify as such 20 to 40% of
Japan, personal communication, Decem- the cases of sore throats,76 several clinical
J Am Soc Nephrol 19: 1855–1864, 2008.
ber 27, 2007) demonstrated by double- scoring systems have been developed to
staining method that NAPlr and SPEB increase the accuracy of diagnosis for the
✤ 糸球体腎炎の機序は未だ完全に解明できていないが, of antibiotics. Among the
both are localized in the glomerular mes- prescription
angium of biopsies of patients with acute most popular are the scores proposed by
Antigenがいくつかは判明している. they found Centor et al.77 and McIsaac et al.78 that
PSGN (Figure 2) and because
similar localization of both antigens postu- have a range from 0 to 4 and incorporate
lated that plasmin-binding activity may be age as a risk factor. The McIsaac score
a common nephritogenic characteristic in gives 1 point each to the following crite-
✤ The nephritis-associated plasmin receptor (NAPlr)と,
both antigens. ria: Temperature Ͼ38°C, no cough, ten-
Streptococcal pyrogenic exotoxin B (SPEB).
Figure 2. Representative photomicrograph. (A and B) Double-immunofluorescence staining
for streptococcal NAPlr (A; Alexa Fluor 594) and SPEB (B; FITC) in a renal biopsy of a patient
with acute PSGN. (C) Similar but not identical distribution of NAPlr and SPEB is observed in
the merged image. Microphotographs contributed by Drs. T. Oda and N. Yoshizawa.
5. Adv Anat Pathol 2012;19:338–347
✤ 基本的にAPSGNでは腎生検は推奨されない.
✤ 非典型的な経過, RPGNを疑う場合,
著明な肉眼的血尿, 高血圧, ネフローゼ合併,
腎外病変合併例では生検を考慮.
✤ また, 6wk以上持続する低補体血症,
Adv Anat Pathol
Volume 19, Number 5, September 2012 Postinfectious Glomerulonephritis
2歳未満の発症, 成人発症例も生検を考慮するポイントとなる.
TABLE 1. Poststreptococcal GN: The Interval Between the Onset of Renal Symptoms and Renal Biopsy Determines the Histologic
Features
Early Biopsy ( 2 wk)
Typical Features Late Biopsy ( 4-6 wk)
Clinical features Mild albuminuria and Acute nephritic syndrome Persistent microscopic
hematuria hematuria and/or
proteinuria
Light microscopy Glomerular endocapillary Diffuse global proliferation (“exudative” early on; Mesangial proliferation
proliferation may be focal lymphocytes, monocytes along with mesangial and
and segmental endothelial proliferation predominate later)
Immunofluorescence C3 and IgG; starry sky C3 and IgG; starry sky or garland pattern* C3 ± IgG; mesangial
microscopy pattern pattern
Electron microscopy Mesangial, subepithelial Mesangial, subepithelial (humps), Mesangial and ± rare
(humps), and ± and ± subendothelial deposits subepithelial humps in the
subendothelial deposits mesangial “notch”
*Garland pattern with confluent subendothelial deposits in patients with nephrotic syndrome.
GN indicates glomerulonephritis; Ig, immunoglobulin.
8. H) PSGNの早期もしくは晩期に生検をした場合,
稀だが局所性, 巣状の糸球体増強が認められる
I) 稀だが半月形成を伴うRPGNパターンも認められる.
al glomerulonephritis (PSGN). A–C, The most common pattern is diffuse proliferation
ative” glomerulonephritis (A, HE, Â400). The C3 staining on Immunofluorescence
ic starry-sky pattern (B, Â 400), which corresponds to mesangial deposits and sub-
(C, Â 4000). D–F, Diffuse proliferative PSGN can be lymphocyte and monocyte rich
posits along the capillary wall are focally confluent (12-2’o clock) resembling a garland
ps (not shown), mesangial (arrowhead) and subendothelial deposits ( ) are seen (F,
Adv Anat Pathol 2012;19:338–347
PSGN include red blood cell casts and interstitial neutrophils ( ) (HE, Â 200). H, Less
9. GURE 1. Histologic patterns in poststreptococcal glomerulonephritis (PSGN). A–C, The most common pattern is diffuse proliferati
h abundant neutrophils, referred to as “exudative” glomerulonephritis (A, HE, Â400). The C3 staining on Immunofluorescen
PSGNの治癒期. メサンギウム細胞の増殖を認め,
croscopy (IF) is prominent with a characteristic starry-sky pattern (B, Â 400), which corresponds to mesangial deposits and su
thelial ( ) “humps” on electron microscopy (C, Â 4000). D–F, Diffuse proliferative PSGN can be lymphocyte and monocyte ri
C3沈着も減少している. 電顕でもHumpの減少を認めている.
h only rare neutrophils (D, Â400). The C3 deposits along the capillary wall are focally confluent (12-2’o clock) resembling a garla
pattern (E, Â 400). On EM, subepithelial humps (not shown), mesangial (arrowhead) and subendothelial deposits ( ) are seen
10,000). G, Tubulointerstitial features of acute PSGN include red blood cell casts and interstitial neutrophils ( ) (HE, Â 200). H, Le
quently, biopsies performed early or late in the course of PSGN show focal and segmental glomerular proliferation ( ) (PAS, Â40
Cellular crescents ( ) are infrequent but crescentic PSGN is well documented (JMS, Â 400). J–L, Resolving PSGN with residu
esangial proliferation ( ) (J, PAS, Â400). The C3 staining is seen on IF, albeit less intense (K, Â400). Ultrastructurally, the deposits a
mesangium (arrowhead) along with a rare subepithelial hump ( ) (L, Â3000).
ections cause GN despite having detectable CIC and of prior streptococcal infections. So, other host factors a
ere is no correlation between the amount of CIC and pathogen characteristics seem to determine the pred
verity of GN.24 Normal patients also have CIC, indicative position and severity of glomerular disease.
40 | www.anatomicpathology.com r 2012 Lippincott Williams Wilki
Adv Anat Pathol 2012;19:338–347
10. TABLE 2. Differential Diagnosis of Postinfectious GN
鑑別診断 Clinical and
Serological Parameter Differential Diagnosis Supporting Features and Other Comments
Elevated ASO titers PSGN Serial estimation of ASO to document elevating or reducing titers helpful;
diagnostic value of NAPlr and SPEB antibodies needs confirmation
Non-nephritogenic streptococcal Indicates streptococcal infection only, does not confirm PSGN
infection
Incidental finding High prevalence of streptococcal infections in general population
Low complement levels PIGN Hypocomplementemia not a universal feature
(C3) MPGN Early cases lack GBM double contours; no resolution in 6 wk; ± C3
nephritic factor; serum cryoglobulins + in cryoglobulinemia
Lupus nephritis Positive lupus serology (ANA, anti-DNA)
Temporal association PSGN Postinfection with a latency of 10-14 d
with infection Nonstreptococcal PIGN Some PIGN have concurrent infections detected after renal presentation
IgA nephropathy Synpharyngitic with no latency
Pathologic feature Differential diagnosis Supporting features and other comments
Exudative GN Acute PIGN Typical in PSGN and some acute nonstreptococcocal infection-associated
GN
DDD, a subset Low C3, + C3 nephritic factor, C3-only on IF, intramembranous dense
deposits, occasional subepithelial humps on EM
MPGN type I Rare histologic pattern
Diffuse proliferative Acute PIGN Documented infection, low complements, dominant C3 on IF,
GN subepithelial humps on EM
(nonexudative) Class IV lupus nephritis Positive lupus serology (ANA, anti-ds DNA), low C3, C4, “full-house”
IF, tubuloreticular inclusions on EM
MPGN GBM double contours if present, suggest MPGN; capillary hyaline
thrombi in cryoglobulinemia
Focal segmental Acute PIGN Documented infection, low complements, dominant C3 on IF,
proliferative GN subepithelial humps on EM
Class III lupus nephritis Positive lupus serology (ANA, anti-ds DNA), low C3, C4, “full-house”
IF, tubuloreticular inclusions on EM
IgA nephropathy Normal complement levels, dominant IgA on IF*, no humps on EM
Mesangial Resolving PIGN Documented infection, low complements, dominant C3 on IF,
hypercellularity subepithelial humps on EM
C3 GN Low C3, normal C4, C3-only on IF, alternate complement pathway
abnormalities
IgA nephropathy Normal serum complement levels, dominant IgA on IF*, no humps on
EM
Membranoproliferative Chronic PIGN (eg, shunt nephritis, Infectious etiology of MPGN confirmed, low complements, dominant C3
GN subacute bacterial endocarditis) on IF, mesangial and subendothelial deposits
C3 GN Low C3, normal C4, C3-only on IF, alternate complement pathway
abnormalities
Crescentic GN Acute PIGN Uncommon; documented infection, low complements,
dominant C3 on IF
Pauci-immune GN If vasculitis + or if no deposits seen, consider ANCA disease
Dominant C3 (on IF) PIGN Documented infection, low complements, subepithelial humps on EM
MPGN (type I/III) IF variable with ± IgM/IgG, subendothelial deposits but no humps on
EM; etiology should be investigated
C3 GN C3 only, intramembranous dense deposits in DDD
Subepithelial humps Acute PIGN Documented infection, glomerular proliferation, low complements,
dominant C3 on IF
DDD, a subset Low C3, + C3 nephritic factor, C3-only on IF, intramembranous dense
deposits
Adv Anat Pathol 2012;19:338–347 Membranous glomerulopathy Several small subepithelial deposits instead of large, fewer humps
11. オーストラリアの438例の解析
Am. J. Trop. Med. Hyg., 85(4), 2011, pp. 703–710
✤ 平均年齢は7歳[0-54], 男性51.6%, 女性48.4%と性差は無し.
APSGN IN NORTHERN AUSTRALIA
✤ 15歳での発症が88.1%を占める.
発症率(/100000pt-y)は,
全体では12.5/100000pt-y
0-14歳では41.4,
14歳では2.1
12. gy in this population. Receiver operating characteristic
ere constructed and the area under the curve com- Journal of Paediatrics and Child Health 43 (2007) 446–450
atter ✤ シドニーの37例の解析
plots and Pearson product–moment correlations
Table 2 Clinical features at presentation and laboratory results
ulated to explore relationships between variables.
Subjects (n = 37)
✤ 平均年齢 8.1歳[2.6-14.1], History of recent infection, n (%) 28 (75.7)
man Research Ethics Committee, Eastern Section, Upper respiratory tract infection, n (%) 17 (45.9)
男性64.9%.
t Sydney Area Health Service granted ethics approval Skin infection, n (%) 11 (29.7)
tudy. This study conforms to the provisions of the Examination findings
n of Helsinki in 1995 (as revised in Edinburgh 2000). Hypertension, n (%) 25 (67.6)
Oedema, n (%) 19 (51.4)
✤ 感染症の既往は75%, Laboratory features
s Haematuria, n (%) 37 (100)
上気道感染が45.9%. 100 × 106 cells/L 28 (75.7)
aphics
10–100 × 106 cells/L 5 (13.5)
37 subjects were identified with PSGN during the Red cells detected on urinalysis only 4 (10.8)
症状は浮腫, 高血圧,
iod. The✤mean age was 8.1 ± 3.5 years (range 2.6–
CC Blyth et al.
Pyuria, n (%) 36 (97.3)
s) (Table 1). More subjects were male (64.9%) and this 100 × 106 cells/L 25 (67.6)
血尿, 膿尿.
stent across all age groups. Country of origin was 10–100 × 106 cells/L 7 (18.9)
in 35 children, with most children born within Aus- White cells detected on urinalysis only 4 (10.8)
ofTable 3 Complications were of Australian Aboriginal,
35 (29.6%) children and outcomes of post-streptococcal Positive throat swab (n = 22)* 6
glomerulonephritis Positive skin swab (n = 5)* 4
Polynesian descent. Two children were siblings and
Positive streptococcal serology, n (%) 35 (94.6)
d concurrent disease. Children lived in predominantly = 37)
Subjects (n
Elevated ASO titre 29 (78.4)
tan or creatinine ULN for age suburbs: only four 30 (81.1%)
Peak outer metropolitan children
Elevated ASK titre 26 (70.3)
rred from rural centres. age
Peak creatinine 2 × ULN for 14 (37.8%)
Elevated ADNaseB titre 24 (64.9)
eptococcal glomerulonephritis was diagnosed (8.3%)
Renal failure requiring dialysis 3 more
Likely source of infection†
y during the second part of the study period; nine(5.6%)
Hypertensive encephalopathy 2 cases
Streptococcal pharyngitis, n (%) 17 (45.9)
97) versus 28 cases (1998–2005), P 0.002. The (5.6%)
Fluid overload requiring respiratory support 2 num-
Pyoderma/impetigo, n (%) 10 (27.0)
es Severe nephritis requiring corticosteroids
did not vary significantly between the cooler and3 (8.3%)
Two or more potential sources of infection, n (%) 5 (13.5)
Persistent hypertension and/or haematuria on 1
months: April to September: 17 cases; October to Unknown, n (%) 5 (13.5)
follow up (n = 14)
0 cases.
13. Pediatrics International (2001) 43, 364–367
Prognosis of APSGN 365
✤ 日本国内の138例の解析 between 1989 and 1997.
Fig. 1 Number of APSGN patients
Fig. 3 Number of APSGN patients indicating month of onset.
Table 1 Clinical features at the onset of the disease
Clinical feature Number %
Hematuria 137 99.3
Proteinuria 114 82.6
Hypocomplementemia 138 100
Elevation of ASOT 125 90.6
Edema 118 85.5
Hypertension 89 64.5
Serum urea 20 mg/dL 48 34.8
Serum creatinine 1.0 mg/dL 2 1.4
Isolation of group-A 51 37.0
beta-hemolytic streptococci
ASOT, antistreptolysin-O titer.
Fig. 3 Number of APSGN patients indicating month of onset.
Fig. 1 Number of Fig. 2 Number of APSGN patients indicating sex and age at
APSGN patients between 1989 and 1997.
onset. (), male; ( ), female. Fig. 3 1,2). In theof APSGN patients were male (60.9%) andonset.
(Figs Number sample, 84 patients indicating month of
Fig. 1 Number of APSGN patients between 1989 and 1997.
54 were female (39.1%). The number of patients admitted
Table each Clinical features at the onset of the disease
1 month of the year is shown in Fig. 3. The frequency
Methods Table 1 Clinical features features at the onsetdiseasedisease
distribution of the clinical at the onset of the of the
Clinical shown in Table 1. Hematuria was present in 137 (99.3%)
is feature Number %
After discharge from the hospital, all patients were regularly Clinical feature in 114 patients (82.6%). An elevated ASOT
and proteinuria Number %
followed up every 1–3 months within the first 2 years and Hematuria was detected in 125 (90.6%) 137 edema was evident
level and 99.3
later on, occasionally, as very few patients had persistent Hematuriapatients (85.5%). The presence of hypertension
in 118
Proteinuria 137
114 99.3
82.6
abnormalities. In addition to clinical evaluation and blood Proteinuria as 126/90 mmHg for patients under 8100
was defined
Hypocomplementemia 114
138 82.6
years
pressure measurements, follow-up studies included routine Elevation of and 140/90 mmHg for those over 8 years. A100
Hypocomplementemia
of age ASOT 138
125 total
90.6
urinalysis and blood examination (total serum proteins, Elevation of ASOT 125 90.6
Edema 89 children (64.5%) had hypertension. Serum creatinine
of 118
Edemablood urea nitrogen (BUN) levels at onset were
118
85.5
85.5
serum albumin or electrophoresis, electrolytes, blood urea, and
Hypertension
Hypertension 8989 64.5
64.5
serum creatinine and serum complement levels (C3 and
Serum0.5~0.2 mg/dL mg/dL
ureaurea 20 and 20~12 mg/dL, 48
20 mg/dL 48respectively. Forty-
Serum children (34.8%) had a serum urea nitrogen level 34.834.8
CH50)). eight over
Serum creatinine 1.0 mg/dL 22
Serum creatinine 1.0 two children (1.4%) had a serum
mg/dL 1.4
1.4
20 mg/dL, but only
Isolation of group-A
Isolation of level over 1.0 mg/dL. There were no patients 37.0
51
creatinine group-A 51 37.0
with
beta-hemolytic streptococci
Results serum creatinine streptococci than 1.5 mg/dL and therefore,
beta-hemolytic levels more
no opportunity to treat any of the patients with dialysis.
ASOT, antistreptolysin-O titer.
ASOT, antistreptolysin-O titer.
The patients’ ages ranged from 3 to 14 years (medium Group A beta-hemolytic streptococci were isolated from
14. APSGNの治療
Current Opinion in Pediatrics 2008, 20:157–162
✤ 基本的に予後は良好であり, 対症療法が主となる.
✤ 体液貯留は利尿薬への反応が良好であり,
利尿薬と塩分制限にて対応.
✤ 高血圧はCa-ch阻害薬が推奨される.
ACE阻害薬, ARBsも推奨されるが, 腎不全増悪, 高K血症に注意.
15. Pediatrics International (2001) 43, 364–367
✤ APSGNの経過; 日本国内の138例のフォロー
366 T Kasahara et al. Fig. 4 Transition of the frequency of hematuria.
✤ 血尿, タンパク尿, 低補体血症(C3, CH50)の推移
血尿陽性率 尿タンパク
陽性率
366 T Kasahara et al.
Fig. 5 Transition of the frequency of proteinuria.
Fig. 4 Transition of the frequency of hematuria. Fig. 6 Transition of the frequency of hypocomplementemi
血尿やタンパク尿は数ヶ月持続する. 低補体血症
hematuria and proteinuria levels of all patients and serum
complements of 125 patients sequentially (Fig. 4–6). Nephrotic
低補体は1ヶ月で7割改善, 2ヶ月で97%改善し number of patients with group A streptococcal infec
syndrome developed in an 8-year-old girl, where her
histological examination constant.9 They concluded that the
remained almost at 42 days showed endocapillary
proliferative glomerulonephritis. outbreak ofurinalysis as confir
subtype was related to the Abnormal APSGN was
フォローに向いている. normalized at 6 months from the onset in this case.not check fo
epidemiologically. Unfortunately, we did
serological type of Streptococcal pyogenes, however,
possible that the T1 subtype of the streptococcal infe
補体が改善しない場合はAPSGN以外を考え Discussion
was prevalent in 1992 in Niigata, as well.
The number of the patients whose age at onset is in
The number of patients with APSGN increased in 1991 and
range of 6–10 years-old is more than the other ages (Fig
腎生検を考慮した方が無難. 1992 throughout Japan and this trend was also found in the
It is conceivable that the number of infant patients is sm
Niigata prefecture during this period (Fig. 1). In the study of
16. Table 5. Long-term prognosis of PSGN: Summary of series published before microarray analysis, and proteomics. 99
Table 5. Long-term prognosis of PSGN: Summary of series now have genome se-
For example, we published before
2000 with 5 to 18 yr of follow-upa
2000 with 5 to 18 yr of follow-upa quences available for 11 strains of group
% of Patients with Positive Finding/
Findings % of A Streptococcus recovered from Finding/
Patients with Positive diverse
Patients Findings Total Patients Followed
Patients Total Patients Followed
types of infection, making this organism
Any abnormality 17.4 174/998
Any abnormality 17.4 one of the most extensively characterized
174/998
Proteinuria 13.8 137/997
Proteinuria 13.8 137/997
of any human bacterial pathogen.100 This
Hypertension 13.8 137/998
Hypertension 13.8 remarkable array of 137/998
new information
Azotemia 1.3 14/1032
a
Azotemia 1.3 14/1032
gives new insight into the pathogenesis of
Data correspond to pooled patients from the studies cited in the text.
86 –93
a
Data correspond to pooled patients from the studies cited in the text.86 –93
Table 6. Long-term prognosis of PSGN: Summary of series published after 2000a
Table 6. Long-term prognosis of PSGN: Summary of series published after 2000a
No. of Patients
Follow-up Albuminuria No. of Patients Hypertension
Hematuria Decreased Renal
Location Followed Follow-up Albuminuria Hematuria
(yr)
Location (%) (%)
Followed (%) Function (%)
(Population) (yr) (%) (%)
(Population)
Maracaibo, Venezuela94 110 (urban and 15 to 18 7.2 5.4 13.7 Increased Scr in 0.9% of
rural) Maracaibo, Venezuela 94 110 (urban and 15 to 18 7.2 patients
the 5.4
Northern Territory, Australia95 63 (rural) Ͼ13 13 (controls rural)
21 (controls Not different Not different from
Northern Territory, Australia
4%)
95 63 7%)
(rural) from controls 13 (controls
Ͼ13 controls 21 (controls
Minas Gerais, Brazil97 56 (rural) 5 8 — 30 4%) (Ccr Ͻ60 ml/min)
8% 7%)
a
Ccr, creatinine clearance; Scr, serum creatinine. Minas Gerais, Brazil97 56 (rural) 5 8 —
a
Ccr, creatinine clearance; Scr, serum creatinine.
J Am Soc Nephrol 19: 1855–1864, 2008.
1860 Journal of the American Society of Nephrology J Am Soc Nephrol 19: 1855–1864, 2008
1860 Journal of the American Society of Nephrology
✤ PSGNの長期予後
✤ 血尿やタンパク尿, 高血圧は数年間は持続する例があり,
短期的なフォローには向かない.
