Acute glomerulonephritis

Japanese: 急性糸球体腎炎

Definition/Concept Acute nephritic syndrome is characterized by the sudden onset of microscopic or macroscopic hematuria, proteinuria, hypertension, decreased glomerular filtration rate, and retention of sodium and water. A representative disease of acute nephritic syndrome is acute glomerulonephritis. A typical case of acute glomerulonephritis is preceded by infection with group A beta-hemolytic streptococcus, followed by a latent period and the onset of the three main symptoms being hematuria, edema, and hypertension. Pathologically, it presents as intratubular proliferative glomerulonephritis. Many pediatric and epidemic cases are cured within 2 to 6 months, but sporadic adult cases have a relatively poor prognosis.
Epidemiology The epidemiology of acute glomerulonephritis has changed significantly over the past 10 to 20 years. In the past, most cases of acute glomerulonephritis were caused by tonsillitis or skin infections due to group A β-hemolytic streptococci (M types 12, 1, 24, etc.), and the disease was called acute poststreptococcal glomerulonephritis (APSGN). The most common age for acute glomerulonephritis was 4 to 12 years old, when the first streptococcal infection occurred. Recently, in developed countries, the incidence of acute pediatric glomerulonephritis and epidemic acute glomerulonephritis has decreased dramatically due to improvements in sanitation and advances in antibiotics. On the other hand, sporadic cases in adults are increasing, and the most common age for acute glomerulonephritis is older. The incidence is higher in men than in women, with a ratio of 2:1, and it often occurs in compromised hosts with alcoholism, diabetes, malignant tumors, etc. Regarding the causative bacteria of infection, the relative frequency of infection caused by staphylococci other than streptococci and Gram-negative bacilli is increasing, and infections by viruses such as pneumococcus, herpes, cytomegalovirus, and Epstein-Barr (EB) virus, rickettsia, fungi, and protozoa are also seen, and the disease is now called acute postinfectious glomerulonephritis (APIGN) rather than APSGN. Currently, the most common foci of infection are upper respiratory tract infections, skin infections, pneumonia, and endocarditis. In diabetes, APIGN often occurs after a skin infection caused by staphylococcus, and can also occur as a complication of diabetic nephropathy.
PathogenesisClassically , acute glomerulonephritis after streptococcal infection was thought to occur when nephritis-inducing antigens enter the bloodstream from the site of infection, and antibodies produced by the patient against these antigens form immune complexes in the bloodstream or in the glomeruli (in situ), which deposit in the glomeruli and activate complement to cause glomerular lesions.Recently, glomerular deposition of nephritis-inducing antigens through non-immunological mechanisms and direct glomerular lesion formation through sustained plasmin activity have also been considered (Figure 11-3-2).Reported nephritis-inducing antigens include the intracellular antigen nephritis-associated plasmin receptor (NAPlr) and the extracellular antigen streptococcal pyrogenic exotoxin B (SPEB).NAPlr and SPEB are found in the glomeruli early in acute glomerulonephritis and in serum during the convalescent phase, and both are thought to directly activate the alternative pathway of complement.
Clinical symptoms begin after a 10-14 day incubation period following infection. Symptoms include hematuria, edema, hypertension, oliguria, and proteinuria, and may be accompanied by nephrosis, acute renal failure, or chronic renal failure. Hematuria is an obligate finding, with gross hematuria seen in one-third of cases. Oliguria is seen 2-3 days before edema. Edema is generally mild and is often seen on the face, especially the eyelids. The cause of edema is retention of sodium and water due to a decrease in glomerular filtration rate, and some cases show overflowing conditions such as cardiomegaly, pleural effusion, and pulmonary congestion. Hypertension is seen in one-half of cases. In adults with existing hypertension, the disease worsens. In most children, the course of the disease follows a latent period (10-14 days), an oliguric period (several days), a diuretic period (several days to one week), a recovery period (1-2 months), and a healing period (2-3 months), with proteinuria disappearing earlier than hematuria. In adults, proteinuria, hematuria, and decreased renal function often persist.
inspection
Grades
1) Urine test:
Hematuria occurs in 100% of cases, and proteinuria is seen in most cases, but is often mild, with nephrosis occurring in less than 10% of cases. Dysmorphic red blood cells, white blood cells, red blood cell casts, white blood cell casts, and granular casts are seen in the sediment.
2) Renal function test:
Glomerular filtration rate (GFR) decreases, and serum creatinine and BUN increase.
3) Serological testing:
In patients with acute post-streptococcal nephritis, antistreptolysin-O (ASO) is often positive; it rises within a few days of infection and returns to normal within 1 to 2 years. The positivity rate of antistrepto kinase (ASK) is less than 50%. A transient decrease in serum complement levels (CH50) is observed in almost all cases, regardless of the infectious bacterium, and returns to normal within 6 to 8 weeks. The decrease in C3 is most significant, while the decreases in C1q and C4 are mild, suggesting that a complement activation mechanism mediated by an alternative pathway is involved. Circulating immune complexes (CIC) are positive in 60 to 80% of cases during the acute phase.
Pathological findings
1) Light microscopic findings:
The appearance is that of diffuse, generalized endocapillary glomerulonephritis. Intratubular proliferation is synonymous with intracapillary proliferation. There is swelling of the glomerulus, hyperkaryosis (infiltration of numerous monocytes and neutrophils within the glomerular capillary loop), proliferation and hypertrophy of endothelial cells, and narrowing of the capillary lumen (Figures 11-3-3A, B). Mesangial cells also increase, particularly during the recovery phase. Crescent formation may also be seen. There are often no significant changes in the renal tubules or interstitium, but cellular infiltration is sometimes observed around the glomerulus.
2) Fluorescent antibody findings:
Granular deposition of C3 (and occasionally IgG) is seen in the glomerular capillary wall and in some parts of the mesangium during the acute phase, and is seen only in the mesangium during the recovery phase. Sorger et al. classified the type of deposition into 1) starry sky type (fine granular deposition resembling stars scattered in the capillary wall; Fig. 11-3-3C), 2) garland type (strong band-like coarse granular deposition in the capillary wall), and 3) mesangium type (granular deposition in the mesangium). The starry sky type is seen in the acute phase, the garland type tends to have a poor prognosis, and the mesangium type is seen in the recovery phase.
3) Glomerular electron microscopic findings:
During the acute phase, lump-shaped subepithelial deposits (humps) are seen (Figure 11-3-3D), but they disappear approximately 6 weeks after onset. When there are a significant number of dense humps, they are called atypical humps and are a sign of poor prognosis.
The diagnostic basis is based on acute glomerulonephritis in Diagnostic Table 11-3-3.
Treatment
1) General treatment:
Symptomatic treatment is the main focus. Patients are required to rest for 1 to 2 months to maintain renal blood flow, and dietary therapy is instituted. A high-calorie diet (approximately 35 kcal/kg/day) is followed throughout all stages of the disease, with protein (0.5 g/kg/day) and salt (0-3 g/kg/day) restrictions in the oliguric and diuretic stages, and the protein (1.0 g/kg/day) and salt (3-5 g/kg/day) restrictions relaxed during the recovery and healing stages.
2) Drug therapy:
In the early stages of the disease, antibiotics such as penicillin or cephalosporins may be used to prevent the infection from continuing or recurring. If there is severe oliguria, edema, or high blood pressure, diuretics and antihypertensive drugs are used. If there is severe renal failure, dialysis is performed. As a general rule, corticosteroids and immunosuppressants are not used, except in special cases accompanied by crescent formation.
Prognosis : In children and epidemic cases, almost all cases will make a complete recovery. In sporadic adult cases, the recovery rate is 28-64%, while persistent renal dysfunction is reported in 27-53%, end-stage renal failure in 4-17%, and death in 4-11%. Elderly people, diabetes, compromised hosts, males, and high serum creatinine levels are risk factors for poor prognosis. [Mizuiri Sonoo]

Table 11-3-3
Findings that are the basis for the diagnosis of acute glomerulonephritis

Table 11-3-3

Figure 11-3-2
Mechanism of pathogenesis of acute post-streptococcal glomerulonephritis ">

Figure 11-3-2

Source : Internal Medicine, 10th Edition About Internal Medicine, 10th Edition Information

Japanese:

定義・概念
　急性腎炎症候群（acute nephritic syndrome）は急激に発症する顕微鏡的あるいは肉眼的血尿，蛋白尿，高血圧，糸球体濾過量の低下，Na・水の貯留を特徴とする．　急性腎炎症候群の代表的疾患が急性糸球体腎炎である．急性糸球体腎炎の典型例はＡ群β溶連菌の先行感染後，潜伏期を経て血尿，浮腫，高血圧を3主徴とし発症する．病理学的には管内増殖性糸球体腎炎を呈する．小児・流行例の多くは2～6カ月で治癒に至るが，成人散発例では比較的予後不良である．
疫学
　急性糸球体腎炎の疫学はこの10～20年で著しく変化した．過去には急性糸球体腎炎の大部分はＡ群β溶連菌（Ｍ型12，1，24など）による扁桃炎もしくは皮膚感染症を原因として発症し，acute poststreptococcal glomerulonephritis（APSGN）という病名が使われていた．好発年齢は溶連菌の初感染を受ける4～12歳であった．最近，先進国では衛生環境の改善や抗菌薬の進歩により小児急性糸球体腎炎や流行性急性糸球体腎炎は激減している．一方，成人の散発例は増加しており，好発年齢も高齢化している．2：1で男性の頻度が高く，アルコール中毒，糖尿病，悪性腫瘍などの易感染性宿主（compromised host）に併発することが多い．感染の起炎菌も溶連菌以外のブドウ球菌，Gram陰性桿菌によるものの相対的頻度が高くなっており，肺炎球菌，ヘルペス，サイトメガロウイルス，Epstein-Barr（EB）ウイルスなどのウイルス，リケッチア，真菌，原虫の感染によるものもみられ，APSGNではなくacute postinfectious glomerulonephritis（APIGN）という病名が使われるようになった．現在，感染巣としては上気道炎，皮膚感染症，肺炎，心内膜炎が多い．糖尿病ではブドウ球菌による皮膚感染症後に多くAPIGNが糖尿病性腎症に合併することもある．
成因
　古典的には溶連菌感染後急性糸球体腎炎は腎炎惹起抗原が感染局所より血中に入り，この抗原に対して患者が産生する抗体が流血中あるいは糸球体（in situ）で免疫複合体を形成し，糸球体に沈着，補体を活性化し糸球体病変を形成すると考えられてきた．最近では腎炎惹起抗原の非免疫学的機序による糸球体沈着，プラスミン活性持続による直接的な糸球体病変形成も考えられている（図11-3-2）．腎炎惹起抗原としては菌体内抗原のnephritis-associated plasmin receptor（NAPlr）と菌体外抗原のstreptococcal pyrogenic exotoxin B （SPEB）などが報告されている．NAPlr，SPEBは急性糸球体腎炎の早期に糸球体沈着がみられ，回復期の血清中にみられ，両者とも直接的に補体のalternative pathwayを活性化するとされている．
臨床症状
　先行感染後10～14日の潜伏期を経て発症する．血尿，浮腫，高血圧，乏尿，蛋白尿があり，ネフローゼ，急性腎不全，慢性腎不全を伴うこともある．血尿は必発所見で肉眼的血尿は1/3の症例にみられる．乏尿は浮腫より2～3日前に認められる．浮腫は一般的には軽く顔面，特に顔瞼にみられることが多い．浮腫の成因はGFRの低下によるNa・水の貯留であり，心拡大，胸水，肺うっ血などの溢水状態のみられる症例もある．高血圧は1/2の症例にみられる．既存高血圧のある成人例では増悪がみられる．経過は小児では潜伏期（10～14日），乏尿期（数日），利尿期（数日～１週），回復期（１～２カ月），治癒期（2～3カ月）の経過をたどるものがほとんどであり，蛋白尿は血尿より早く消失する．成人例では蛋白尿，血尿，腎機能低下が遷延することが多い．
検査
成績
1）尿検査：
血尿は100％に，蛋白尿もほとんどの症例でみられるが軽度のことが多く，ネフローゼを呈するのは10％以下である．沈渣では変形赤血球，白血球，赤血球円柱，白血球円柱，顆粒円柱などがみられる．
2）腎機能検査：
糸球体濾過量（GFR）は減少する．血清クレアチニン，BUNの上昇がある．
3）血清学的検査：
溶連菌感染後急性腎炎ではantistreptolysin-O（ASO）が陽性であることが多く，感染後数日で上昇し1～2年で正常化する．antistrepto kinase（ASK）の陽性率は50％未満である．一過性の血清補体価（CH50）の低下は感染を生じた菌にかかわらずほぼ全例で認められ，6～8週以内に正常化する．C3の減少がもっとも著しく，C1q，C4の低下は軽度であり，alternative pathwayを介した補体活性化機序が考えられている．流血中免疫複合体（circulating immune complex：CIC）は急性期には60～80％の症例で陽性である．
病理所見
1）光顕所見：
びまん性全節性の管内増殖性糸球体腎炎（endocapillary glomerulonephritis）の像を呈する．管内増殖は毛細血管内増殖と同義語である．糸球体の腫大，富核（糸球体毛細血管係蹄内の多数の単球，好中球の浸潤），内皮細胞の増殖・肥大，毛細血管腔の狭小化がある（図11-3-3A，B）．メサンギウム細胞も増加し，特に回復期には著しい．半月体形成のみられることもある．尿細管，間質には著変がないことが多いが，ときに糸球体周囲に細胞浸潤を認める．
2）蛍光抗体所見：
C3（ときにIgG）の顆粒状沈着が急性期には糸球体係蹄壁および一部メサンギウムにみられ，回復期にはメサンギウムのみにみられる．Sorgerらは沈着様式により①starry sky型（係蹄壁の星を散りばめたような細顆粒状沈着；図11-3-3C），②garland型（係蹄壁の強い帯状の粗大顆粒状沈着），③mesangium型（メサンギウムの顆粒状沈着）に分けた．starry sky型は急性期にみられ，garland型は予後不良の傾向があり，mesangium型は回復期にみられる．
3）糸球体電顕所見：
急性期では瘤状の上皮下沈着物（hump）がみられるが（図11-3-3D），発症後約6週で消褪する．humpが著しく多数で，密に存在するものはatypical humpとよばれ予後不良の徴候である．
診断
　表11-3-3の急性糸球体腎炎の診断根拠による．
治療
1）一般療法：
対症療法が主体である．腎血流量保持のため1～2カ月間安静し，食事療法を行う．全病期，高エネルギー（約35 kcal/kg/日）食とし，乏尿期，利尿期は蛋白（0.5 g/kg/日）と食塩（0〜3 g/kg/日）を制限し，回復期，治癒期は蛋白（1.0 g/kg/日）と食塩（3〜5 g/kg/日）の制限をゆるめる．
2）薬物療法：
病初期にはペニシリン，セフェム系などの抗生剤を感染の持続・再燃防止のため用いる事もある．乏尿・浮腫・高血圧が著しいときは利尿薬，降圧薬を用いる．腎不全が高度であれば透析を行う．副腎皮質ステロイド，免疫抑制薬は半月体形成を伴う特殊例以外，原則的には用いない．
予後
　小児，流行例ではほぼ全例完全治癒に至る．成人散発例での治癒率は28～64％であり，持続性腎機能低下が27～53％，末期腎不全が4～17％，死亡が4～11％と報告されている．高齢者，糖尿病，compromised host，男性，血清クレアチニン高値が予後不良の危険因子である．［水入苑生］

表11-3-3
急性糸球体腎炎の診断根拠となる所見">

表11-3-3

図11-3-2
溶連菌感染後急性糸球体腎炎の発生機序">

図11-3-2

出典　内科学第10版内科学第10版について　情報

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