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.
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 HistologicFeatures 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 proteinuriaLight 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 patternElectron 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.
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 proliferationative” 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 richposits along the capillary wall are focally confluent (12-2’o clock) resembling a garlandps (not shown), mesangial (arrowhead) and subendothelial deposits ( ) are seen (F, Adv Anat Pathol 2012;19:338–347PSGN include red blood cell casts and interstitial neutrophils ( ) (HE, Â 200). H, Less
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 garlapattern (E, Â 400). On EM, subepithelial humps (not shown), mesangial (arrowhead) and subendothelial deposits ( ) are seen10,000). G, Tubulointerstitial features of acute PSGN include red blood cell casts and interstitial neutrophils ( ) (HE, Â 200). H, Lequently, biopsies performed early or late in the course of PSGN show focal and segmental glomerular proliferation ( ) (PAS, Â40Cellular crescents ( ) are infrequent but crescentic PSGN is well documented (JMS, Â 400). J–L, Resolving PSGN with residuesangial 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 aere is no correlation between the amount of CIC and pathogen characteristics seem to determine the predverity 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
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 depositsAdv Anat Pathol 2012;19:338–347 Membranous glomerulopathy Several small subepithelial deposits instead of large, fewer humps
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-y0-14歳では41.4,14歳では2.1
gy in this population. Receiver operating characteristicere constructed and the area under the curve com- Journal of Paediatrics and Child Health 43 (2007) 446–450atter ✤ シドニーの37例の解析 plots and Pearson product–moment correlations Table 2 Clinical features at presentation and laboratory resultsulated 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 featuress 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 1months: April to September: 17 cases; October to Unknown, n (%) 5 (13.5) follow up (n = 14)0 cases.
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
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.
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
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 before2000 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 organismAny abnormality 17.4 174/998 Any abnormality 17.4 one of the most extensively characterized 174/998Proteinuria 13.8 137/997 Proteinuria 13.8 137/997 of any human bacterial pathogen.100 ThisHypertension 13.8 137/998 Hypertension 13.8 remarkable array of 137/998 new informationAzotemia 1.3 14/1032a 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 –93Table 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 5.4Northern 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 (controlsMinas 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.