今日の臨床サポート

急性腎炎

著者: 鶴屋和彦 九州大学大学院 包括的腎不全治療学

監修: 岡田浩一 埼玉医科大学 腎臓内科

著者校正/監修レビュー済:2021/11/10
参考ガイドライン:
  1. KDIGO Clinical Practice Guideline for Glomerulonephritis
患者向け説明資料

概要・推奨   

  1. 溶連菌感染後急性糸球体腎炎の急性期治療は、適切な血圧管理と体液管理が望ましいOG推奨度1)
  1. 溶連菌感染後急性糸球体腎炎は、5~12歳の学童と60歳以降の高齢者に好発する。社会環境と発症リスクが関連しており、近年、先進国では発症数が低下してきている。
  1. 先行感染後に急激に血圧上昇、浮腫を来した症例では、溶連菌感染後急性糸球体腎炎の可能性がある。特に、学童期発症の場合、その可能性はさらに高まる。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要とな
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要
  1. C3変換酵素の構成因子であるFactor Bに対する自己抗体が一過性に存在することにより、補体の代替経路が活性化される[1]
  1. 治療の基本は対症療法になるが、6カ月以上1g/日以上の尿蛋白が持続する例は予後不良で、アンジオテンシン変換酵素(ACE)阻害薬やアンジオテンシンII受容体拮抗薬(ARB)を投与する(OG、推奨度1)。また、広範囲に半月体が認められ、急速進行性糸球体腎炎の経過を呈する場合、ステロイドパルス療法を考慮する(OG、推奨度2)[2]
薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
鶴屋和彦 : 未申告[2021年]
監修:岡田浩一 : 講演料(協和キリン,中外製薬,田辺三菱,第一三共),研究費・助成金など(協和キリン),奨学(奨励)寄付など(協和キリン,中外製薬,田辺三菱,第一三共,アステラス,MSD,武田薬品,鳥居薬品,ファイザー,ノバルティス,日本ベーリンガーインゲルハイム,大塚製薬,塩野義,大日本住友)[2021年]

改訂のポイント:
  1. 定期レビューを行い、感染関連糸球体腎炎(infection‒related glomerulonephritis、IRGN)や半月体を伴う場合のステロイド治療について加筆修正を行った。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. 急性腎炎(acute glomerulonephritis、AGN)は、WHO臨床症候分類で、「先行感染後、比較的急な経過で発症し、血尿、蛋白尿とともに、浮腫、乏尿、高血圧、糸球体濾過量の減少を認める疾患」と定義されている。ただし、先行感染が明白でない場合でも同様の症状を呈すれば、急性腎炎と診断される。
  1. かつては、感染を契機に急性発症する糸球体腎炎の80~90%が、A群β溶連菌による扁桃炎もしくは皮膚感染症を原因とする溶連菌感染後急性糸球体腎炎(acute post-streptococcal glomerulonephritis、APSGN)であったが、近年は、小児に多く認められる予後良好なAPSGN例が減少し、高齢者において溶連菌以外の感染症を原因とする症例も多く認められるようになり、感染関連糸球体腎炎(infection‒related glomerulonephritis、IRGN)と総称されるようになった。黄色ブドウ球菌や表皮ブドウ球菌による糸球体腎炎(staphylococcus infection-associated glomerulonephritis、SAGN)が多く、APSGNと比較して予後不良で、高齢者、とくに糖尿病や悪性腫瘍などの合併症を有する患者は高リスクとされる。
  1. APSGNについては、先進国での発症は減少傾向にあるが、発展途上国、特に熱帯・亜熱帯地域での発症は減少していない。
 
  1. 溶連菌感染後急性糸球体腎炎は、社会環境と発症リスクが関連しており、近年、先進国では発症数が低下してきている。
  1. かつては、溶連菌感染後急性糸球体腎炎が小児腎炎の多くを占めていたが、先進国では発症数が減少しつつある[3]。全世界での発症数は年間47万人であり、人口10万人当たり9.5~28.5人/年に相当する[4][5]。その97%は発展途上国での発症である。この傾向は、急性腎炎のみならず、溶連菌による咽頭炎、リウマチ熱の発症数にも同様に認める。したがって、発症に衛生環境や栄養状況などの社会的な因子が大きく関与していると考えられる。
問診・診察のポイント  
  1. 数週間以内の先行感染の有無を確認する。

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文献 

著者: Sophie Chauvet, Romain Berthaud, Magali Devriese, Morgane Mignotet, Paula Vieira Martins, Tania Robe-Rybkine, Maria A Miteva, Aram Gyulkhandanyan, Amélie Ryckewaert, Ferielle Louillet, Elodie Merieau, Guillaume Mestrallet, Caroline Rousset-Rouvière, Eric Thervet, Julien Hogan, Tim Ulinski, Bruno O Villoutreix, Lubka Roumenina, Olivia Boyer, Véronique Frémeaux-Bacchi
雑誌名: J Am Soc Nephrol. 2020 Apr;31(4):829-840. doi: 10.1681/ASN.2019080851. Epub 2020 Feb 7.
Abstract/Text BACKGROUND: The pathophysiology of the leading cause of pediatric acute nephritis, acute postinfectious GN, including mechanisms of the pathognomonic transient complement activation, remains uncertain. It shares clinicopathologic features with C3 glomerulopathy, a complement-mediated glomerulopathy that, unlike acute postinfectious GN, has a poor prognosis.
METHODS: This retrospective study investigated mechanisms of complement activation in 34 children with acute postinfectious GN and low C3 level at onset. We screened a panel of anticomplement protein autoantibodies, carried out related functional characterization, and compared results with those of 60 children from the National French Registry who had C3 glomerulopathy and persistent hypocomplementemia.
RESULTS: All children with acute postinfectious GN had activation of the alternative pathway of the complement system. At onset, autoantibodies targeting factor B (a component of the alternative pathway C3 convertase) were found in a significantly higher proportion of children with the disorder versus children with hypocomplementemic C3 glomerulopathy (31 of 34 [91%] versus 4 of 28 [14%], respectively). In acute postinfectious GN, anti-factor B autoantibodies were transient and correlated with plasma C3 and soluble C5b-9 levels. We demonstrated that anti-factor B antibodies enhance alternative pathway convertase activity in vitro, confirming their pathogenic effect. We also identified crucial antibody binding sites on factor B, including one correlated to disease severity.
CONCLUSIONS: These findings elucidate the pathophysiologic mechanisms underlying acute postinfectious GN by identifying anti-factor B autoantibodies as contributing factors in alternative complement pathway activation. At onset of a nephritic syndrome with low C3 level, screening for anti-factor B antibodies might help guide indications for kidney biopsy to avoid misdiagnosed chronic glomerulopathy, such as C3 glomerulopathy, and to help determine therapy.

Copyright © 2020 by the American Society of Nephrology.
PMID 32034108  J Am Soc Nephrol. 2020 Apr;31(4):829-840. doi: 10.1681/・・・
著者:
雑誌名: Kidney Int Suppl (2011). 2012 Jun;2(2):209-217. doi: 10.1038/kisup.2012.23.
Abstract/Text
PMID 25018935  Kidney Int Suppl (2011). 2012 Jun;2(2):209-217. doi: 10・・・
著者: S Roy, F B Stapleton
雑誌名: Pediatr Nephrol. 1990 Nov;4(6):585-8.
Abstract/Text Changing perspectives in 95 children with poststreptococcal acute glomerulonephritis (PSAGN) in our hospital between 1979 and 1988 are reported. Between 1961 and 1970 an average of 31 +/- 6.3 patients/year with PSAGN were treated and 70% had antecedent pyoderma. In the present study antecedent pharyngitis was observed in 59 children and pyoderma in 36. In comparison to the decade ending in 1970 our data show: (1) a marked decline in the prevalence of PSAGN (P = less than 0.0005), (2) a predominance of antecedent pharyngeal infection (P = 0.044), (3) a decline in urban and an increase in rural patients with PSAGN (P = 0.0483); and in the last decade: (1) a predominance of antecedent pharyngeal infection in children over 6 years of age (P = 0.0009) and (2) a predominance of antecedent pyoderma in black children (P = 0.0004).

PMID 2088456  Pediatr Nephrol. 1990 Nov;4(6):585-8.
著者: Bernardo Rodriguez-Iturbe, James M Musser
雑誌名: J Am Soc Nephrol. 2008 Oct;19(10):1855-64. doi: 10.1681/ASN.2008010092. Epub 2008 Jul 30.
Abstract/Text Poststreptococcal glomerulonephritis is one of the oldest recognized renal diseases. In the past three decades, significant changes have occurred in its epidemiology, in new insight gained in the nephritogenic characteristics of streptococcal antigens, and in the natural history of the disease. The disease is now rare in industrialized nations, but in the underprivileged world, the burden of poststreptococcal glomerulonephritis ranges between 9.5 and 28.5 new cases per 100,000 individuals per year. Prophylactic antibiotic treatment is advisable in epidemic conditions and to household contacts of index cases in communities where the prevalence of the disease is high. The long-term prognosis is variable; in general, prognosis is excellent in children but significantly worse when it occurs in elderly individuals and in populations that present other risk factors of chronic kidney disease. Contemporary large-scale research strategies such as genome-wide sequencing may uncover new information about pathogenic factors contributing to disease.

PMID 18667731  J Am Soc Nephrol. 2008 Oct;19(10):1855-64. doi: 10.1681・・・
著者: Jonathan R Carapetis, Andrew C Steer, E Kim Mulholland, Martin Weber
雑誌名: Lancet Infect Dis. 2005 Nov;5(11):685-94. doi: 10.1016/S1473-3099(05)70267-X.
Abstract/Text The global burden of disease caused by group A streptococcus (GAS) is not known. We review recent population-based data to estimate the burden of GAS diseases and highlight deficiencies in the available data. We estimate that there are at least 517,000 deaths each year due to severe GAS diseases (eg, acute rheumatic fever, rheumatic heart disease, post-streptococcal glomerulonephritis, and invasive infections). The prevalence of severe GAS disease is at least 18.1 million cases, with 1.78 million new cases each year. The greatest burden is due to rheumatic heart disease, with a prevalence of at least 15.6 million cases, with 282,000 new cases and 233,000 deaths each year. The burden of invasive GAS diseases is unexpectedly high, with at least 663,000 new cases and 163,000 deaths each year. In addition, there are more than 111 million prevalent cases of GAS pyoderma, and over 616 million incident cases per year of GAS pharyngitis. Epidemiological data from developing countries for most diseases is poor. On a global scale, GAS is an important cause of morbidity and mortality. These data emphasise the need to reinforce current control strategies, develop new primary prevention strategies, and collect better data from developing countries.

PMID 16253886  Lancet Infect Dis. 2005 Nov;5(11):685-94. doi: 10.1016/・・・
著者: Odile Becquet, Jérôme Pasche, Hélène Gatti, Claude Chenel, Michel Abély, Patrice Morville, Christine Pietrement
雑誌名: Pediatr Nephrol. 2010 Feb;25(2):275-80. doi: 10.1007/s00467-009-1325-4. Epub 2009 Oct 30.
Abstract/Text The aim of this study was to define the current demographic, clinical and prognostic characteristics of acute post-streptococcal glomerulonephritis (APSGN) in French Polynesia and to compare these features with those of other populations. Fifty children, all of whom were <15 years old and had been admitted to the Territorial Hospital of Papeete for APSGN between January 2005 and December 2007, were retrospectively enrolled in the study. Diagnostic criteria were microscopic or macroscopic haematuria, decreased C3 fraction of the complement and evidence of recent streptococcal infection. The annual incidence was 18 cases per 100,000 children <15 years of age in 2007. Most of the children (98%) enrolled in the study were of Polynesian ethnic origin, 27 were male (54%), and the average age at presentation was 6.7 years. Signs of previous respiratory infections were clearly evident in 40% of the children. Most of the patients presented during the rainy season, correlating with the relatively high incidence of skin infections at this time. The majority of patients had proteinuria (98%), with 25% having proteinuria in the nephrotic range (proteinuria/urinary creatinine >3 g/g). The presentation was severe in 22% of the children (congestive cardiac failure, severe hypertension and/or encephalopathy), and renal failure was an initial presenting symptom in 43.7%. The C3 fraction was lower in severe presentations, but the type of haematuria, level of proteinuria and inflammatory syndrome were not correlated with immediate severe forms or with initial renal failure. Haematuria resolved in a mean of 7.7 months and proteinuria in a mean of 3.9 months. None of the children had hypocomplementemia for more than 8 weeks. Acute post-streptococcal glomerulonephritis is endemic among French Polynesians, and they can be considered to be a high-risk population. Despite a high incidence of skin infections, however, the predominance of respiratory infections potentially indicates that French Polynesia is on the way to become a low-incidence area. Systematic detection and treatment of group A Streptococcus should be intensified.

PMID 19876655  Pediatr Nephrol. 2010 Feb;25(2):275-80. doi: 10.1007/s0・・・
著者: I Sagel, G Treser, A Ty, N Yoshizawa, H Kleinberger, A M Yuceoglu, E Wasserman, K Lange
雑誌名: Ann Intern Med. 1973 Oct;79(4):492-9.
Abstract/Text
PMID 4795879  Ann Intern Med. 1973 Oct;79(4):492-9.
著者: J E Lewy, L Salinas-Madrigal, P B Herdson, C L Pirani, J Metcoff
雑誌名: Medicine (Baltimore). 1971 Nov;50(6):453-501.
Abstract/Text
PMID 4942418  Medicine (Baltimore). 1971 Nov;50(6):453-501.
著者: S Sanjad, A Tolaymat, J Whitworth, S Levin
雑誌名: South Med J. 1977 Oct;70(10):1202-6.
Abstract/Text Clinical experience with 153 cases of acute glomerulonephritis is recorded. Streptococcal impetigo was the major causative factor in this series. The acute fatality rate was 1.3% (two patients). Of the 151 survivors, 103 patients have been followed up for periods of six months to 11 years. None of these patients have shown any evidence of progression to chronic glomerulonephritis. In this series, as in others previously reported, acute glomerulonephritis in children appears to be self-limited in contrast to the illness in adults, where 25% to 40% of the cases progress to chronic glomerulonephritis. Unusual findings in this survey were ten patients with minimal or no urine abnormalities. Ten patients had normal serum complement values and three patients had well documented second attacks of poststreptococcal glomerulonephritis.

PMID 333598  South Med J. 1977 Oct;70(10):1202-6.
著者: E L Kaplan, B F Anthony, S S Chapman, E M Ayoub, L W Wannamaker
雑誌名: J Clin Invest. 1970 Jul;49(7):1405-14. doi: 10.1172/JCI106358.
Abstract/Text The immune response after streptococcal infection of the skin and of the upper respiratory tract (URT) was studied prospectively in a group of normal children, ages 3-6 yr. The children were examined and cultures for group A streptococci were obtained weekly from the throat, nose, and skin lesions (when present). Paired sera were collected at the beginning and end of the study, and the changes in antibody titers were measured for three different streptococcal antigens: streptolysin O, deoxyribonuclease B (DNAse B), and nicotinamide adenine dinucleotidase (NADase). The findings suggest that in contrast to infection of the URT antibody response to streptolysin O is relatively feeble after streptococcal infection which is limited to the skin. The response to NADase is also poor after cutaneous infection. Antibody responses to DNAse B are generally good regardless of the site of the infection. These and other studies indicate that anti-DNAse B is the antibody of choice in studying streptococcal infection of the skin and its complications.

PMID 5432372  J Clin Invest. 1970 Jul;49(7):1405-14. doi: 10.1172/JCI・・・
著者: E M Ayoub, L W Wannamaker
雑誌名: Pediatrics. 1966 Dec;38(6):946-56.
Abstract/Text
PMID 5928726  Pediatrics. 1966 Dec;38(6):946-56.
著者: T Matthew Eison, Bettina H Ault, Deborah P Jones, Russell W Chesney, Robert J Wyatt
雑誌名: Pediatr Nephrol. 2011 Feb;26(2):165-80. doi: 10.1007/s00467-010-1554-6. Epub 2010 Jul 23.
Abstract/Text Post-streptococcal acute glomerulonephritis (PSAGN) is one of the most important and intriguing conditions in the discipline of pediatric nephrology. Although the eventual outcome is excellent in most cases, PSAGN remains an important cause of acute renal failure and hospitalization for children in both developed and underdeveloped areas. The purpose of this review is to describe both the typical and less common clinical features of PSAGN, to outline the changes in the epidemiology of PSAGN over the past 50 years, and to explore studies on the pathogenesis of the condition with an emphasis on the search for the elusive nephritogenic antigen.

PMID 20652330  Pediatr Nephrol. 2011 Feb;26(2):165-80. doi: 10.1007/s0・・・
著者: L A RANTZ, E RANDALL, H H RANTZ
雑誌名: Am J Med. 1948 Jul;5(1):3-23.
Abstract/Text
PMID 18867849  Am J Med. 1948 Jul;5(1):3-23.
著者: Christopher C Blyth, Peter W Robertson, Andrew R Rosenberg
雑誌名: J Paediatr Child Health. 2007 Jun;43(6):446-50. doi: 10.1111/j.1440-1754.2007.01109.x.
Abstract/Text AIM: Post-streptococcal glomerulonephritis (PSGN) is a frequent cause of acute nephritis in children. Numerous studies have described PSGN in high-risk populations yet few data describing PSGN in a low-incidence population exist. This study aimed to describe the epidemiology, clinical manifestations, diagnosis, complications and outcomes of PSGN in an urban Australian population.
METHODS: A 16-year retrospective review of case notes and laboratory data was conducted at a tertiary Sydney paediatric hospital.
RESULTS: Thirty-seven children were treated for PSGN with a mean age of 8.1 years (range 2.6-14.1 years). Twenty-eight subjects (75.7%) had a history of a recent upper respiratory tract or skin infection. Hypertension and/or oedema was present in 29 subjects (78.4%). Streptococcal pharyngitis was identified as the likely source in 17 subjects (45.9%). Skin infections occurred less frequently. Antibodies against streptolysin O, streptokinase or deoxyribonuclease B were elevated when a single titre was measured in 35 subjects (94.6%). Thirty subjects (81.1%) developed renal impairment (median peak creatinine, 95 micromol/L, range 39-880 micromol/L). No correlation was demonstrated between peak creatinine, age, ethnicity, streptococcal titres and serum complement levels. The mean length of admission was 8.2 days. Seven subjects (18.9%) had a complicated course with three subjects requiring dialysis. Only one subject has ongoing renal dysfunction.
CONCLUSION: Significant differences are seen in a low-incidence urban Australian population with PSGN when compared with endemic or epidemic disease in high-risk populations. The higher rates of complications that were seen compared with previously studied populations need further clarification.

PMID 17535174  J Paediatr Child Health. 2007 Jun;43(6):446-50. doi: 10・・・
著者: F Ferrario, O Kourilsky, L Morel-Maroger
雑誌名: Clin Nephrol. 1983 Jan;19(1):17-23.
Abstract/Text 30 renal biopsies were performed in 20 adult patients with acute diffuse endocapillary glomerulonephritis. 11 patients who presented with acute renal failure (ARF) and 9 patients who had normal or mildly altered renal function were compared in order to look for clinical or pathologic features peculiar to each group and possible differences in outcome. All patients underwent early renal biopsy, and 8 had repeat biopsies. There were no significant differences in clinical, immunologic or histologic features between the two groups. In repeat biopsies, there were no histologic nor immunohistologic differences between patients with or without initial ARF. After a mean follow-up period of 18 months, the overall clinical outcome appeared favorable and was similar in the two groups. Thus, initial ARF in patients with acute endocapillary glomerulonephritis does not imply a bad prognosis. The recognition of pure endocapillary proliferation in patients with anuric acute glomerulonephritis by means of renal biopsy may avoid unnecessary and potentially hazardous treatment.

PMID 6339129  Clin Nephrol. 1983 Jan;19(1):17-23.
著者: D S Baldwin
雑誌名: Am J Med. 1977 Jan;62(1):1-11.
Abstract/Text
PMID 319660  Am J Med. 1977 Jan;62(1):1-11.
著者: D S Baldwin, M C Gluck, R G Schacht, G Gallo
雑誌名: Ann Intern Med. 1974 Mar;80(3):342-58.
Abstract/Text
PMID 4816174  Ann Intern Med. 1974 Mar;80(3):342-58.
著者: M Washio, Y Oh, S Okuda, T Yanase, C Miishima, S Fujimi, N Ohchi, F Nanishi, K Onoyama, M Fujishima
雑誌名: Clin Nephrol. 1994 May;41(5):265-70.
Abstract/Text In order to characterize the clinical features in elderly patients with poststreptococcal glomerulonephritis (PSGN), 31 patients, who were both histologically and immunologically proven to be PSGN, were divided up into 3 groups according to age; elderly patients being 55 years or older (n = 7), middle-aged patients being 40 to 54 years old (n = 7) and younger patients being 20 to 39 years old (n = 17). Renal functional impairment as indicated by serum creatinine levels of over 2.0 mg/dl, developed in 4 of the elderly patients and later completely improved at the end of the follow-up period (178.9 +/- 150.7 days). On the other hand, none of the middle-aged and younger patients revealed any renal function impairment. Hypertension was observed more frequently in elderly patients than in younger patients, and was 86% and 6% at the time of admission, respectively. In addition, 43% of elderly patients remained hypertensive at the time of discharge. There was no difference in total protein, ASO, CH50, the degree of proteinuria or proliferative and exudative features in renal histology among the three groups. None of the elderly patients with PSGN died or developed persistent renal failure. In conclusion, elderly patients with PSGN had a high incidence of renal functional impairment and hypertension compared to the younger patients on admission, however, their short-term prognosis seems to be favorable.

PMID 8050205  Clin Nephrol. 1994 May;41(5):265-70.
著者: E J Lewis, C B Carpenter, P H Schur
雑誌名: Ann Intern Med. 1971 Oct;75(4):555-60.
Abstract/Text
PMID 4106150  Ann Intern Med. 1971 Oct;75(4):555-60.
著者: J S Cameron, R M Vick, C S Ogg, W M Seymour, C Chantler, D R Turner
雑誌名: Br Med J. 1973 Sep 29;3(5882):668-72.
Abstract/Text As part of a larger study of serial complement profiles in glomerulonephritis plasma C3 and C4 concentrations were measured using commercially available immunodiffusion plates. A total of 303 samples were obtained from 128 patients suffering from forms of nephritis associated with hypocomplementaemia-namely, lupus nephritis, mesangiocapillary glomerulonephritis (M.C.G.N.), and acute glomerulonephritis.These simple measurements of C3 and C4 gave clinically useful information. In lupus nephritis C3 and C4 generally correlated and C4 concentrations were more often and more profoundly depressed than C3 concentrations. Neither C3 nor C4 concentrations alone correlated well with the antinuclear factor titre.In both acute glomerulonephritis and M.C.G.N. the C3 concentrations were frequently lower than 20% of normal (which was never the case in patients with lupus), while the C4 concentration was usually normal and was almost never depressed in the absence of C3 depression. This suggests activation of complement at the C3 level by the "bypass" pathway in acute nephritis as well as in M.C.G.N., though both may be operating in some patients. In acute glomerulonephritis but not in M.C.G.N. C3 concentrations returned to normal within eight to 12 weeks.The two varieties of M.C.G.N. identified by the site of the deposits in the capillary glomerular walls differed in their C3 levels. In 10 patients with intramembranous dense linear deposits the C3 was always low over very long periods of time, rising in three out of four patients only after transplantation and immunosuppression. Other patients with M.C.G.N., in contrast, often showed normal C3 concentrations. Concentrations of C4 did not differ in either group, being normal in 80% of samples from all types.

PMID 4200478  Br Med J. 1973 Sep 29;3(5882):668-72.
著者: S Roy, W M Murphy, B S Arant
雑誌名: J Pediatr. 1981 Mar;98(3):403-10.
Abstract/Text Crescenteric glomerulonephritis preceded by a streptococcal infection with creatinine clearance CCr of less than 30 ml/minute/1.73 m2 was treated by supportive care plus three months of quintuple therapy (prednisone, azathioprine, cyclophosphamide, dipyridamole, and heparin followed by warfarin) in five children (Group A) or by supportive care alone in five others (Group B). Of the glomeruli examined, 69.8 +/- 11.7% (mean +/- SE) in Group A and 64.4 +/- 10.6% in Group B had crescents which involved 54.0 +/- 10.8% and 60.0 +/- 10.5% of glomerular circumference, respectively. Clinical and histologic findings supported a recent streptococcal infection in every patient. Two patients from Group A had mild proteinuria and normal CCr at 12 months; one died abruptly of pulmonary hemorrhage after maintaining a normal CCr for 25 months. Following a second episode of poststreptococcal acute glomerulonephritis seven months after the first, one patient from Group B had persistent mild proteinuria for 41 months and hypertension through 56 months of follow-up. Nine surviving patients have maintained normal CCr for eight to 60 months (mean 29.5 months). The findings of this study suggest that this quintuple therapy offers no advantage over supportive care in the clinical management and outcome of children with severe crescenteric glomerulonephritis when an antecedent streptococcal infection is confirmed by serologic and histopathologic criteria.

PMID 7205449  J Pediatr. 1981 Mar;98(3):403-10.
著者: K Sorger, U Gessler, F K Hübner, H Köhler, W Schulz, W Stühlinger, G H Thoenes, W Thoenes
雑誌名: Clin Nephrol. 1982 Mar;17(3):114-28.
Abstract/Text 42 kidney biopsies from adults and children suffering from acute postinfectious glomerulonephritis were examined by light microscopy, immunofluorescence and electron microscopy. The biopsies were obtained within 9 weeks of the onset of the first clinical symptoms. The results show not only a range of variation in the histological picture (particularly in the accumulation of leukocytes in the capillary lumens, and in the degree of cell proliferation) but also different immunofluorescent patterns which we have called the "starry sky", "garland" and "mesangial" patterns. These patterns correspond to characteristic differences in the electron microscopic picture. The "starry sky" pattern (IgG, IgM and/or IgA, combined with C3) occurs mainly in the first weeks of the disease and is associated with an endocapillary-mesangial glomerulonephritis. This may turn into a "mesangial" pattern (mostly C3 alone) which is associated mainly with mesangial proliferation. Four types of immune deposits can be observed electron microscopically in all three patterns (subendothelial, subepithelial, mesangial and intramembranous), but their different quantitative distribution determines the characteristic picture. Subepithelial deposits (so called "humps") often considered characteristic of poststreptococcal glomerulonephritis play a dominant role in the "garland" pattern. The cases with a "garland" pattern often show strikingly high levels of proteinuria (greater than 5 g/24 hr). It is believed that in patients with postinfectious glomerulonephritis deposition of immune complexes of various composition is responsible for producing the described subtypes depending on their different distribution in the glomeruli. It seems possible that these subtypes have different clinical significance, something which could be confirmed by performing follow-up studies.

PMID 7067173  Clin Nephrol. 1982 Mar;17(3):114-28.
著者: K Sorger, M Gessler, F K Hübner, H Köhler, H Olbing, W Schulz, G H Thoenes, W Thoenes
雑誌名: Clin Nephrol. 1987 Mar;27(3):111-24.
Abstract/Text Quantitative correlative investigations by means of light, immunofluorescence and electron microscopy carried out in the early phase of the disease on 58 patients (children and adults) with acute postinfectious glomerulonephritis (APGN) formed the basis of subtyping APGN into a starry sky type, a mesangial type and a garland type [Sorger et al. 1982 and 1983]. The subtypes also showed differences in the clinical picture. The garland type was of special interest since most patients had severe proteinuria. This caused us to follow-up the patients with these three subtypes (up to 10 years and 7 months). Proteinuria proved to be the most reliable follow-up parameter. A comparison of the three groups showed that proteinuria rapidly declined as a rule in the patients with the starry sky and the mesangial patterns. In the garland pattern there were also cases with a complete disappearance of proteinuria, especially in younger patients, but other patients still had a distinct proteinuria after months to years indicating a protracted or chronic course. The morphological findings of the rebiopsies correlated with the clinical courses, especially with the course of proteinuria. The three morphological subtypes are thus significant for estimating the prognosis of APGN, which is favorable as a rule in patients with the starry sky and mesangial types, but much more unfavorable in patients with the garland type. Even if fewer cases with demonstrated streptococcal etiology were found in the garland pattern group, i.e., among patients with the most uncertain prognosis, than in the remaining groups, these differences were not statistically significant. Therefore, our investigations do not provide any indications that different etiological factors are responsible for the three subtypes. The individual immune response of the host body is likely to be very much more decisive.

PMID 3552342  Clin Nephrol. 1987 Mar;27(3):111-24.
著者: R Poon-King, J Bannan, A Viteri, G Cu, J B Zabriskie
雑誌名: J Exp Med. 1993 Aug 1;178(2):759-63.
Abstract/Text Examination of the extracellular products of nephritis(+) and nephritis(-) group A streptococci revealed the presence of a 46-kD protein secreted by nephritogenic strains that binds to human plasmin. Immunological data revealed that this protein, called nephritis plasmin binding protein (NPBP), is not related to group A streptokinase nor to a recently described streptococcal dehydrogenase protein. The binding of human plasmin to this protein can be blocked by epsilon-amino caproic acid, indicating the importance of lysine groups in the binding process. Mutanolysin extracts of cell walls from these nephritogenic strains probed with anti-NPBP antibody were negative for cell wall-bound NPBP. Serological data with acute poststreptococcal glomerulonephritis (APSGN) and acute rheumatic fever sera indicated that the protein reacts preferentially with APSGN sera. Amino acid sequence analysis and immunological reactivity suggest NPBP is the streptococcal pyrogenic exotoxin B precursor, also previously described as zymogen (streptococcal proteinase precursor). The secretion of both group A streptokinase and a secreted plasmin binding protein in the same nephritogenic strain raises an intriguing hypothesis of the mechanisms of action of this protein in APSGN.

PMID 8340765  J Exp Med. 1993 Aug 1;178(2):759-63.
著者: S S D'Costa, M D Boyle
雑誌名: Methods. 2000 Jun;21(2):165-77. doi: 10.1006/meth.2000.0988.
Abstract/Text A series of methods for analyzing the interaction of group A streptococci with the human plasminogen system are described. Examples of group A streptococcal isolates capable of assembling surface plasminogen activator activity when grown in human plasma are presented and the key requirements for this process are evaluated. The stabilities of cell-associated plasmin and plasminogen activator complexes are compared and a model for the interaction of group A streptococci with the plasminogen system in an infected host is presented.

Copyright 2000 Academic Press.
PMID 10816378  Methods. 2000 Jun;21(2):165-77. doi: 10.1006/meth.2000.・・・
著者: K Yamakami, N Yoshizawa, K Wakabayashi, A Takeuchi, T Tadakuma, M D Boyle
雑誌名: Methods. 2000 Jun;21(2):185-97. doi: 10.1006/meth.2000.0990.
Abstract/Text Immunoglobulin G from a patient convalescing from acute poststreptococcal glomerulonephritis (APSGN) bound specific antigenic sites in early APSGN glomeruli. A streptococcal cytoplasmic antigen (preabsorbing antigen, PA-Ag), could selectively preabsorb fluorescein isothiocyanate (FITC)-labeled IgG and prevented glomerular staining. The antigen was purified and identified as an M(r) approximately 43,000 protein with a pI of 4.7 that strongly activated complement C3 (N. Yoshizawa, S. Oshima, I. Sagel, J. Shimizu, and G. Treser, 1992, J. Immunol. 148, 3110-3116). In the present study, a nephritogenic antigen was purified by affinity chromatography using APSGN IgG-immobilized Sepharose followed by chromatography on an anion-exchange resin. Purification was monitored by ELISA and Western blotting using the binding characteristics of the specific antibodies present in APSGN serum. The molecular weight of the purified antigen, named nephritis-associated plasmin receptor (NAPlr), was an M(r) approximately 43,000 protein and the internal amino acid sequence was found to be homologous to those of the plasmin receptor (Plr) of group A streptococci strain 64/14 and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from Bacillus subtilis. The purified NAPlr exhibited GAPDH activity and plasmin(ogen) binding activity. Using FITC-labeled rabbit anti-NAPlr, the antigen was found to be present in the glomeruli of 22 of 22 patients in the early stage of APSGN. Bacterial Plr was also demonstrated in human APSGN glomeruli for the first time using monoclonal antibody to the recombinant Plr protein. Antibody to NAPlr was found in the sera of 46 of 50 (92%) patients within 3 months of onset. These results led us to speculate that NAPlr bound to the glomeruli may contribute to the pathogenesis of APSGN via plasmin and complement activation.

Copyright 2000 Academic Press.
PMID 10816380  Methods. 2000 Jun;21(2):185-97. doi: 10.1006/meth.2000.・・・
著者: N Yoshizawa, K Yamakami, T Oda
雑誌名: Kidney Int. 2006 Mar;69(5):942-3; author reply 942. doi: 10.1038/sj.ki.5000175.
Abstract/Text
PMID 16518356  Kidney Int. 2006 Mar;69(5):942-3; author reply 942. doi・・・
著者: Nobuyuki Yoshizawa, Kazuo Yamakami, Masayuki Fujino, Takashi Oda, Kikuko Tamura, Koichi Matsumoto, Tetsuzo Sugisaki, Michael D P Boyle
雑誌名: J Am Soc Nephrol. 2004 Jul;15(7):1785-93.
Abstract/Text The role of nephritis-associated antigen as a virulence factor for acute poststreptococcal glomerulonephritis (APSGN) remains to be fully clarified. Nephritis-associated plasmin receptor (NAPlr) was previously isolated from group A streptococcus (GAS) and shown to bind plasmin(ogen). The nucleotide sequence of the naplr gene from GAS isolates obtained from patients with APSGN was determined. The sequence of the putative open reading frame (1011 bp) showed 99.8% identity among isolated strains. Homology screen revealed an exact match with streptococcal glyceraldehyde-3-phosphate dehydrogenase (GAPDH). NAPlr exhibited GAPDH activity in zymography, and it activated the complement pathway in vitro. In APSGN kidney biopsy specimens, NAPlr was observed mainly in the early stage of the disease (1 to 14 d after onset) but was not colocalized with either C3 or IgG as assessed by double immunofluorescence staining. Sera of patients with APSGN, patients with GAS infection without renal involvement, nonrenal pediatric patients, and healthy adults as controls were assayed for anti-NAPlr antibody titers. Anti-NAPlr antibodies were present most frequently in APSGN sera, and antibody titers were also significantly higher than in patients with GAS infection alone or in other control patients. Moreover, antibody titers remained elevated during the entire 10-yr follow-up period.

PMID 15213266  J Am Soc Nephrol. 2004 Jul;15(7):1785-93.
著者: Takashi Oda, Nobuyuki Yoshizawa, Kazuo Yamakami, Aki Ishida, Osamu Hotta, Shigenobu Suzuki, Soichiro Miura
雑誌名: Nephrol Dial Transplant. 2007 Mar;22(3):740-8. doi: 10.1093/ndt/gfl712. Epub 2007 Jan 5.
Abstract/Text BACKGROUND: Glomerular hypercellularity due to resident glomerular cell proliferation and leucocyte infiltration has been described in acute post-streptococcal glomerulonephritis (APSGN). APSGN usually resolves without progression. However, the mechanism of resolution remains to be determined.
METHODS: Renal biopsy tissues from 15 patients with APSGN (obtained 1-31 days after disease onset) and five control patients with minor glomerular abnormality were evaluated with respect to glomerular resolution. Apoptotic cells were assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) as well as by immunostaining of single-stranded DNA (ssDNA).
RESULTS: The number of glomerular cells was high in the early-phase of APSGN and decreased over time. No TUNEL+ glomerular cells were found in control subjects, whereas prominent glomerular TUNEL+ cells were observed in APSGN patients, particularly in the early phase of the disease. The number of glomerular TUNEL+ cells decreased exponentially but was still prominent in renal tissue biopsied at 31 days after disease onset. Double staining for ssDNA and glomerular cell markers showed that glomerular apoptotic cells were predominantly mesangium and endothelial cells, with some neutrophils and macrophages.
CONCLUSIONS: These results suggest that apoptosis exists in the glomerulus in patients with APSGN from the early to the late stages of the disease and contributes to the resolution of glomerular hypercellularity.

PMID 17205964  Nephrol Dial Transplant. 2007 Mar;22(3):740-8. doi: 10.・・・
著者: Takashi Oda, Nobuyuki Yoshizawa, Kazuo Yamakami, Kikuko Tamura, Aki Kuroki, Tetsuzo Sugisaki, Emi Sawanobori, Kohsuke Higashida, Yoshiyuki Ohtomo, Osamu Hotta, Hiroo Kumagai, Soichiro Miura
雑誌名: Hum Pathol. 2010 Sep;41(9):1276-85. doi: 10.1016/j.humpath.2010.02.006. Epub 2010 Jun 17.
Abstract/Text The nephritis-associated plasmin receptor is a recently identified nephritogenic antigen associated with acute poststreptococcal glomerulonephritis and proposed to play a pathogenic role, but its precise glomerular localization in acute poststreptococcal glomerulonephritis has not been elucidated. We therefore analyzed renal biopsy sections from 10 acute poststreptococcal glomerulonephritis patients by using immunofluorescence staining with anti-nephritis-associated plasmin receptor antibody and various markers of glomerular components. Nephritis-associated plasmin receptor was detected in the glomeruli of all patients, and double staining for nephritis-associated plasmin receptor and collagen IV showed nephritis-associated plasmin receptor to be predominantly on the inner side of the glomerular tufts. Nephritis-associated plasmin receptor-positive areas within glomerular tufts were further characterized with markers for neutrophils, mesangial cells, endothelial cells, and macrophages. In 6 of the patients, nephritis-associated plasmin receptor staining was seen mainly in neutrophils and to a lesser degree in mesangial and endothelial cells. In the other 4 patients, nephritis-associated plasmin receptor staining was seen mainly in mesangial cells and to a lesser degree in neutrophils and endothelial cells. In all patients, macrophages showed little staining. Elevated plasmin activity in glomerular neutrophils was identified by combining in situ zymography staining for plasmin activity and immunofluorescence staining for neutrophils. The glomerular localizations of nephritis-associated plasmin receptor and another nephritogenic antigen, streptococcal pyrogenic exotoxin B, were compared by double immunofluorescence staining and found to be similar. These findings indicate the nephritogenic potential of nephritis-associated plasmin receptor and offer valuable information with respect to the pathogenic mechanism of acute poststreptococcal glomerulonephritis.

Copyright 2010 Elsevier Inc. All rights reserved.
PMID 20708459  Hum Pathol. 2010 Sep;41(9):1276-85. doi: 10.1016/j.hump・・・
著者: Takashi Oda, Nobuyuki Yoshizawa, Kazuo Yamakami, Yutaka Sakurai, Hanako Takechi, Kojiro Yamamoto, Naoki Oshima, Hiroo Kumagai
雑誌名: J Biomed Biotechnol. 2012;2012:417675. doi: 10.1155/2012/417675. Epub 2012 Oct 14.
Abstract/Text It is well known that glomerulonephritis can occur after streptococcal infection, which is classically referred to as acute poststreptococcal glomerulonephritis (APSGN). The pathogenic mechanism of APSGN has been described by so-called immune complex theory, which involves glomerular deposition of nephritogenic streptococcal antigen and subsequent formation of immune complexes in situ and/or the deposition of circulating antigen-antibody complexes. However, the exact entity of the causative antigen has remained a matter of debate. We isolated a nephritogenic antigen for APSGN from the cytoplasmic fractions of group A streptococcus (GAS) depending on the affinity for IgG of APSGN patients. The amino acid and the nucleotide sequences of the isolated protein revealed to be highly identical to those of reported plasmin(ogen) receptor of GAS. Thus, we termed this antigen nephritis-associated plasmin receptor (NAPlr). Immunofluorescence staining of the renal biopsy tissues with anti-NAPlr antibody revealed glomerular NAPlr deposition in essentially all patients with early-phase APSGN. Furthermore, glomerular plasmin activity was detected by in situ zymography in the distribution almost identical to NAPlr deposition in renal biopsy tissues of APSGN patients. These data suggest that NAPlr has a direct, nonimmunologic function as a plasmin receptor and may contribute to the pathogenesis of APSGN by maintaining plasmin activity.

PMID 23118507  J Biomed Biotechnol. 2012;2012:417675. doi: 10.1155/201・・・
著者: M Beaufils, L Morel-Maroger, J D Sraer, A Kanfer, O Kourilsky, G Richet
雑誌名: N Engl J Med. 1976 Jul 22;295(4):185-9. doi: 10.1056/NEJM197607222950402.
Abstract/Text We studied 11 patients who had visceral abscesses and in whom acute renal failure developed. All renal biopsies showed a diffuse proliferative and crescentig glomerulonephritis. In seven patients blood cultures were repeatedly negative. Endocarditis could be ruled out in six patients. Seven patients had circulating cryoglobulins; serum complement levels were normal in seven and decreased in four; circulating immune complexes were found in the three patients studied. The evolution of the glomerulonephritis, documented by serial biopsies, closely paralleled the course of the infection. A complete recovery of renal function occurred in four cases in which a rapid and complete cure of the infection was obtained. Of five patients in whom the infection was not cured, four died, and chronic renal failure developed in one. In two patients in whom therapy was delayed, chronic renal failure also developed. Deep suppuration, even in the absence of bacteremia, may be responsible for a severe but possibly reversible glomerulonephritis with circulating immune complexes.

PMID 1272347  N Engl J Med. 1976 Jul 22;295(4):185-9. doi: 10.1056/NE・・・
著者: R S Dobrin, N K Day, P G Quie, H L Moore, H L Vernier, A F Michael, A J Fish
雑誌名: Am J Med. 1975 Nov;59(5):660-73.
Abstract/Text We describe three patients with arrested hydrocephalus in whom glomerulonephritis developed secondary to Staphylococcus epidermidis bacteremia from an infected ventriculoatrial shunt. Investigation of the immune-mediated renal disease associated with this chronic infection showed that (1) complement depletion during the acute phase of bacteremia and nephritis was predominantly via the classic pathway; (2) rheumatoid factor was associated with bacteremia, fever, proteinuria and low complement levels; (3) early complement components (C1q, C4, C3), immunoglobulin (predominantly immunoglobulin M [IgM], Staph. epidermidis antigen(s) and electron denxe subendothelial deposits were localized within the renal glomerulus; (4) C1q, and IgM derived from patient serums, were the most prominent in vitro immunoreactants to Staph. epidermidis cell walls; and (5) the causative organisms, Staph. epidermidis, shared common antigens with Staph. aureus, and antibody from patient serums cross reacted with extracts from both of these organisms.

PMID 1106192  Am J Med. 1975 Nov;59(5):660-73.
著者: G Baehr
雑誌名: J Exp Med. 1912 Apr 1;15(4):330-47.
Abstract/Text 1. In most cases of chronic or subacute bacterial endocarditis due to the endocarditis coccus (Streptococcus viridans), there exists a distinctive pathological lesion in some of the glomeruli due to bacterial emboli. 2. The salient features of the pathological picture are first, the involvement of one or more loops of a variable number of glomeruli; secondly, the absence of any visible disease in the uninvolved glomeruli and in the uninvolved portions of affected glomeruli; and thirdly, the association in most of the bacterial cases of all the various stages of the glomerular process often seen in a single microscopical section. 3. The lesion does not occur in cases of acute endocarditis, and up to the present time it has been absent in cases of subacute bacterial endocarditis due to organisms other than the endocarditis coccus. 4. In a group of cases having vegetations that are typical of those in the active stage of subacute endocarditis (except that they are free from bacteria and healing or healed), the healed stage of this distinctive glomerular lesion is present, although it is less extensive than in the active bacterial cases. 5. These cases, therefore, are most probably examples of subacute bacterial endocarditis due originally to the endocarditis coccus, but in which the endocardial vegetations have become free from bacteria rather early in their course and are now healing or healed, as claimed by Harbitz and Libman. 6. During the active bacterial stage of the disease, if the glomerular lesions are not too numerous, the only symptoms produced will be an almost constant hematuria, usually demonstrable only microscopically. If the glomerular lesions are very numerous, symptoms resembling those of subacute hemorrhagic nephritis may occur and may even cause a fatal issue. If the glomerular lesions are very numerous but not sufficient to cause death, and the cardiac lesion should go on to healing, a contracted kidney, secondary to the glomerular lesion, may subsequently ensue and produce the typical symptoms and death. In such a case, the finding of the healed or healing lesion of subacute bacterial endocarditis will be accidental.

PMID 19867526  J Exp Med. 1912 Apr 1;15(4):330-47.
著者: Enrico Pola, Giandomenico Logroscino, Vincenzo De Santis, Filippo Canducci, Antonio Delcogliano, Antonio Gasbarrini
雑誌名: Arthroscopy. 2003 Apr;19(4):E29. doi: 10.1053/jars.2003.50118.
Abstract/Text Septic arthritis is rare in patients undergoing knee arthroscopic surgery. If the infection is due to Staphylococcus aureus, patients might experience fever, severe clinical syndromes, and extra-articular manifestations, including vasculitis and glomerulonephritis. We describe a case of onset of immunoglobulin A nephropathy (Berger disease) after S aureus septic arthritis complicating an anterior cruciate ligament surgical reconstruction. The patient had no previous history of renal disease, and renal function returned to normal after resolution of the knee infection. S aureus infection has been associated with several glomerular diseases, but this is the first report of the infection causing immunoglobulin A nephropathy. In addition, this is the first description of Berger disease after arthroscopic treatment, providing evidence that this disease might complicate the clinical course of orthopedic surgery.

PMID 12671604  Arthroscopy. 2003 Apr;19(4):E29. doi: 10.1053/jars.2003・・・
著者: Robert Peel, Leslie Sellars, Ervine D Long, Sunil Bhandari
雑誌名: Am J Kidney Dis. 2003 Jan;41(1):E1. doi: 10.1053/ajkd.2003.50019.
Abstract/Text Backache, a common symptom, is rarely caused by infection of the lumbar discs. The authors present the case of a 60-year-old man with a Staphylococcus aureus septicemia and associated lumbar discitis in whom a pauci immune crescentic glomerulonephritis and renal failure developed. Treatment with antibiotics and not immunosuppressive agents resulted in improved renal function with a discharge creatinine level of 1.87 mg/dL (165 micromol/L). This case highlights an association of pauci-immune crescentic glomerulonephritis with discitis that responded to antibiotic therapy alone.

Copyright 2003 by the National Kidney Foundation, Inc.
PMID 12500252  Am J Kidney Dis. 2003 Jan;41(1):E1. doi: 10.1053/ajkd.2・・・
著者: M D Griffin, J Björnsson, S B Erickson
雑誌名: J Am Soc Nephrol. 1997 Oct;8(10):1633-9.
Abstract/Text A 72-year-old man developed acute renal failure after coronary bypass surgery that had been complicated by sternal osteomyelitis caused by the Staphylococcus aureus bacterium. Bacteremia and sepsis were not present. Renal biopsy demonstrated a florid, diffuse, proliferative glomerulonephritis with glomerular immune complex deposition. Management included hemodialysis, prolonged antibiotic therapy, and repeated surgical debridement. Spontaneous recovery of renal function occurred after eradication of infection and final surgical wound repair. The relationship between acute bacterial infections and glomerulonephritis and, in particular, the causal role of staphylococcal antigens in the pathogenesis of such lesions is discussed.

PMID 9335395  J Am Soc Nephrol. 1997 Oct;8(10):1633-9.
著者: K Yoh, M Kobayashi, A Hirayama, K Hirayama, N Yamaguchi, S Nagase, A Koyama
雑誌名: Clin Nephrol. 1997 Nov;48(5):311-6.
Abstract/Text A case in which the enterotoxins of Staphylococcus aureus may have served as bacterial superantigens is presented. This 71-year-old man developed proteinuria and renal dysfunction after contacting pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA), coagulase type II. The infection occurred after surgery for recurrent lung cancer. Staphylococcus enterotoxins B, C, and TSST-1 were detected from the bacillus. Ten days after the onset of pneumonia, proteinuria was noted; urinary protein was as high as 1.8 g/day. The serum creatinine was elevated from 1.0 mg/dl to 3.7 mg/dl. Several immunological reactions were detected; the serum levels of IgG and IgA were increased, and the selective usage of T-cell receptor V beta (TCRV beta) was observed. Serum levels of IL-1 beta, IL-2, IL-6, IL-8, IL-12, and tumor necrosis factor alpha (TNF alpha) were also elevated. Examination of the renal biopsy specimen by light microscopy showed minor to mild mesangial proliferative glomerulonephritis. Immunofluorescence microscopy demonstrated the deposition of IgG, IgA, and C3, mainly along the capillary walls. Electron microscopy revealed electron dense deposits, mainly in the subepithelial areas, and injury to the glomerular basement membrane. When the pneumonia improved following antibiotic therapy, the renal function also improved, and proteinuria decreased. The levels of immunoglobulins and the usage of TCRV beta also decreased. Because staphylococcus enterotoxins act as superantigens, we believe this to be a typical case of superantigen-related glomerulonephritis.

PMID 9403216  Clin Nephrol. 1997 Nov;48(5):311-6.
著者: Y Yamashita, T Tanase, Y Terada, H Tamura, T Akiba, H Inoue, T Ida, S Sasaki, F Marumo, Y Nakamoto
雑誌名: Intern Med. 2001 May;40(5):424-7.
Abstract/Text A 58-year-old man developed proteinuria and renal dysfunction following pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin was administered, and prednisolone pulse therapy and plasmapheresis were performed. Subsequently, serum creatinine was decreased. Eight months later, creatinine and CRP were again elevated, and MRSA was detected. Vancomycin was again administered and plasmapheresis was performed. However, renal function was not improved and continuous hemodialysis was initiated. This case indicates that complete eradication of MRSA is necessary to treat MRSA-associated glomerulonephritis, and if this is not attained, a permanent loss of renal function occurs.

PMID 11393416  Intern Med. 2001 May;40(5):424-7.
著者: A Koyama, M Kobayashi, N Yamaguchi, K Yamagata, K Takano, M Nakajima, F Irie, M Goto, M Igarashi, T Iitsuka
雑誌名: Kidney Int. 1995 Jan;47(1):207-16.
Abstract/Text We report 10 cases of glomerulonephritis following methicillin-resistant Staphylococcus aureus (MRSA) infection. The clinical features of this syndrome were an abrupt or insidious onset of rapidly progressive glomerulonephritis (RPGN) with nephrotic syndrome and occasionally purpura, following MRSA infection. The renal histologic findings showed a variety of types of proliferative glomerulonephritis with varying degrees of crescent formation; immunofluorescence revealed of glomerular deposition of IgA, IgG, and C3. Laboratory findings showed polyclonal increases of serum IgA and IgG, with high levels of circulating immune complexes (ICs). Increased numbers of DR+CD4+, and DR+CD8+T cells were observed in the peripheral circulation, with a high frequency of T cell receptor (TCR) V beta + cells. MRSA produced enterotoxins C and A and toxic shock syndrome toxin (TSST)-1, all of which are known to act as superantigens. From the above observations, we speculate that post-MRSA glomerulonephritis may be induced by superantigens causing production of high levels of cytokines, and polyclonal activation of IgG and IgA. The formation of ICs containing IgA and IgG in the circulation result in development of glomerulonephritis and vasculitis. Accordingly, microbial superantigens may play an important role in the pathogenesis of this unique syndrome of nephritis and vasculitis.

PMID 7731148  Kidney Int. 1995 Jan;47(1):207-16.
著者: T Kasahara, H Hayakawa, S Okubo, T Okugawa, N Kabuki, S Tomizawa, M Uchiyama
雑誌名: Pediatr Int. 2001 Aug;43(4):364-7.
Abstract/Text BACKGROUND: Recently, the prognosis of acute poststreptococcal glomerulonephritis (APSGN) has been reported as improved, compared with the results of previous studies. In an attempt to clarify this, we analyzed the clinical course of patients with APSGN.
METHODS: A total of 220 children with acute nephritic syndrome were treated in the affiliated hospitals of our department, between January 1988 and December 1997. Among them, 138 children who were diagnosed with APSGN according to the presence of hematuria, transient hypocomplementemia and evidence of group A beta-hemolytic streptococcal infection, were studied.
RESULTS: Serum creatinine and blood urea nitrogen levels at onset were 0.5 +/- 0.2 mg/dL and 20 +/-12 mg/dL, respectively. There were no patients with renal dysfunction (serum creatinine level > or = 1.5 mg/dL), but one patient with nephrotic syndrome. Blood pressure was well controlled in all patients and there were no patients with persistent hypertension. Serum complement levels were normalized within 12 weeks (100%), hematuria disappeared within 4 years (100%) and proteinuria disappeared within 3 years (100%) from the onset.
CONCLUSIONS: These data indicate that the prognosis of APSGN during childhood is excellent, when adequately diagnosed and treated.

PMID 11472580  Pediatr Int. 2001 Aug;43(4):364-7.
著者: S W Pinto, R Sesso, E Vasconcelos, Y J Watanabe, A M Pansute
雑誌名: Am J Kidney Dis. 2001 Aug;38(2):249-55. doi: 10.1053/ajkd.2001.26083.
Abstract/Text In 1998 there was a large outbreak of acute glomerulonephritis (GN) in Nova Serrana, Brazil, caused by group C Streptococcus zooepidemicus and linked to the consumption of contaminated cheese produced with unpasteurized milk. This study describes the follow-up of these patients after a mean of 2 years following the acute episode. Of 134 patients identified in 1998, 69 patients were reexamined and underwent measurements of blood pressure, 24-hour creatinine clearance, microalbuminuria (radioimmunoassay), and urine sediment analysis. Of the original group of 134 patients, 3 patients died in the acute phase and 5 patients (3.7%) required chronic dialysis. Of 69 patients reevaluated, 65 patients (94%) were adults (mean age, 39 +/- 2 [SE] years) and 47 patients (68%) were women. At the follow-up examination, we found arterial hypertension in 42% of subjects (27 of 64 subjects), serum creatinine levels greater than 1.2 mg/dL in 12% (10 of 68 subjects), reduced creatinine clearance (<80 mL/min/1.73 m(2)) in 30% (20 of 67 subjects, 2 of them on chronic dialysis therapy), and increased microalbuminuria (>20 microg/min) in 34% (22 of 65 subjects). Increased microalbuminuria and/or reduced creatinine clearance were detected in 48% of the subjects (31 of 65 subjects). Patients with microalbuminuria had greater diastolic blood pressure than those without microalbuminuria (mean, 98 +/- 4 versus 88 +/- 2 mm Hg; P = 0.02). In conclusion, after a mean of 2 years, patients with epidemic poststreptococcal GN caused by S zooepidemicus present a high rate of hypertension and frequent abnormalities of renal function, with some having reached end-stage renal disease. Longer follow-up will be important to define the prognosis of these patients.

PMID 11479149  Am J Kidney Dis. 2001 Aug;38(2):249-55. doi: 10.1053/aj・・・
著者: D S Baldwin
雑誌名: Kidney Int. 1982 Jan;21(1):109-20.
Abstract/Text
PMID 7077942  Kidney Int. 1982 Jan;21(1):109-20.
著者: J W Lien, T H Mathew, R Meadows
雑誌名: Q J Med. 1979 Jan;48(189):99-111.
Abstract/Text The long-term outcome after acute post-streptococcal glomerulonephritis was studied in 57 patients (52 aged 16 or over) followed for a period of one to 14 years (mean seven years). All patients presented with hypertension, haematuria and proteinuria. The antistreptolysin-0 titre was raised or the serum complement was low in all cases at the initial episode. All patients had histological evidence of a diffuse proliferative and exudative glomerulonephritis at onset. Follow-up renal biopsy was performed in 33 patients; in 18 patients this was carried out five years or more after the initial illness. Five patients died beyond two years, only two having had abnormal renal function at the time or death. Four patients were found to be mildly hypertensive without other clinical abnormalities. Eleven patients had proteinuria, haematuria or abnormal renal function; in three of these repeat renal biopsy was normal, incomplete resolution was reported in five, obsolescent glomeruli in one, and two others were not biopsied. No patient who had normal renal function at the time of follow-up had abnormal renal histology on biopsy. Obsolescent glomeruli were present in two other biopsies in association with evidence of incomplete resolution. It was concluded that the majority of patients with acute PSGN have a good prognosis. Histological resolution of the renal lesion may not occur for nine years.

PMID 482595  Q J Med. 1979 Jan;48(189):99-111.
著者: Wendy E Hoy, Andrew V White, Alison Dowling, Suresh K Sharma, Hilary Bloomfield, Bernard T Tipiloura, Cheryl E Swanson, John D Mathews, David A McCredie
雑誌名: Kidney Int. 2012 May;81(10):1026-32. doi: 10.1038/ki.2011.478. Epub 2012 Feb 1.
Abstract/Text Although unusual in western countries and in Australia in general, post-streptococcal glomerulonephritis (PSGN) is still common in Australian Aboriginal children living in remote communities. Here, we evaluated whether episodes of acute PSGN increased the risk for chronic kidney disease in later life in 1519 residents of a remote Aboriginal community (85% of those age eligible), with high rates of renal and cardiovascular disease, who participated in a health screen over a 3-year period. Of these, 200 had had at least one episode of PSGN, with 27 having had multiple episodes, usually in childhood. High levels of albuminuria (albumin/creatinine ratio) with increasing age were confirmed. All PSGN episodes were associated with group A streptococcal skin infections, often related to scabies. In both genders, aged 10-39 years at screening, about one in five had such a history. Among them, PSGN (5 years or more earlier) was significantly associated with higher levels of albuminuria than those without. In women, aged 30-39 years, a history of PSGN was associated with a significantly higher frequency of estimated glomerular filtration rates <60 ml/min. The adjusted odds ratios for an albumin/creatinine ratio over 34 g/mol (overt albuminuria) in males and females with a history of PSGN were 4.6 and 3.1, respectively, compared with those without a history. Thus, PSGN contributes to the very serious burden of chronic kidney disease in this community. Rigorous strategies to prevent scabies and Group A streptococcal infections will reduce this burden.

PMID 22297679  Kidney Int. 2012 May;81(10):1026-32. doi: 10.1038/ki.20・・・
著者: Shashidhar Baikunje, Mahesha Vankalakunti, A Nikith, A Srivatsa, Suhan Alva, Janardhan Kamath
雑誌名: Clin Kidney J. 2016 Apr;9(2):222-6. doi: 10.1093/ckj/sfv147. Epub 2016 Jan 20.
Abstract/Text BACKGROUND: Crescent formation generally reflects severe glomerular injury. There is sparse literature on post-infectious glomerulonephritis (PIGN) with crescents in adults. This retrospective study looked at nine such cases to see if there is a correlation between the severity of presentation, steroid treatment, histological severity and outcome.
METHODS: Biopsy reports of all the adults who underwent kidney biopsy from February 2010 to June 2014 in a tertiary care hospital were screened and all the cases with the diagnosis of PIGN with crescents were selected. Clinical presentation, laboratory data, histology, treatment and outcome were analysed.
RESULTS: Six patients had evidence of recent/current infection, but all except two were non-streptococcal. The mean creatinine was 360.67 μmol/L (range 70.72-770.85) and the mean estimated glomerular filtration rate (MDRD eGFR) was 30.28 mL/min/1.73 m(2) (range 6.4-111.1) on presentation. All five patients who were treated with steroids had an excellent response. Among the four patients who did not receive steroids, two were left with significant renal impairment (mean MDRD eGFR 23.5 mL/min/1.73 m(2)) at a mean follow-up of 15.5 months (range 10-21). The mean percentage of glomeruli with crescents was 36.13% (range 11.76-100) and except in one, there was no tubular atrophy or interstitial fibrosis and none had glomerulosclerosis. None of the patients progressed to end-stage renal disease.
CONCLUSION: Non-streptococcal infections are more common precipitants. There was no correlation between histological and clinical severity. Patients treated with steroids had better renal outcomes.

PMID 26985372  Clin Kidney J. 2016 Apr;9(2):222-6. doi: 10.1093/ckj/sf・・・
著者: Ramanathan Sakthirajan, Jeyachandran Dhanapriya, Mani Nagarajan, Thanigachalam Dineshkumar, T Balasubramaniyan, Natarajan Gopalakrishnan
雑誌名: Saudi J Kidney Dis Transpl. 2018 May-Jun;29(3):623-629. doi: 10.4103/1319-2442.235169.
Abstract/Text The epidemiology of infection-related glomerulonephritis (IRGN) is changing in recent times both in developed and developing nations. Although published studies showed renal outcome in adult IRGN was not as benign as in children, literature regarding clinical profile and outcome of crescentic form of adult IRGN is scarce; hence, we aimed to study the clinical profile of crescentic IRGN. We conducted a retrospective observational study in patients with crescentic IRGN in adults at the Department of Nephrology, Madras medical college, Chennai between 2009 and 2014. A total of 47 patients were included with a mean follow-up of 9.9 ± 4.2 months. The mean age was 42 ± 13.5 years. About 19.1% of patients had diabetes. The skin was the most common site of infection (38.3%) with methicillin-resistant Staphylococcus acareas (MRSA) as the most common organism. Hypocomplementemia was present in 100% in our study. Hemodialysis (HD) was required in 53.2% of patients and oral steroids were given in 78.7%. Complete renal recovery was seen only in 25.5%, progression to chronic kidney disease in 40.4%, seven patients reached end-stage renal disease, and nine patients died during follow-up. On univariate analysis, MRSA infection, the unidentified source of infection, nonisolation of organisms presence of interstitial fibrosis and tubular atrophy in renal biopsy and requirement of HD were found to be significant risk factors for poor renal outcome. In our study, crescentic form of IRGN is associated with poor renal outcome.

PMID 29970739  Saudi J Kidney Dis Transpl. 2018 May-Jun;29(3):623-629.・・・

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