Antistreptolysin O titer

Email this page to a friendBookmark & SharePrinter-friendly version Antistreptolysin O (ASO) titer is a blood test to measure antibodies against streptolysin O, a substance produced by group A Streptococcus bacteria. How the Test is Performed A blood sample is needed. For information on how this is done, see: Venipuncture How to Prepare for the Test You should not eat for 6 hours before the test. How the Test Will Feel When the needle is inserted to draw blood, you may feel moderate pain, or only a prick or stinging sensation. Afterward, there may be some throbbing. Why the Test is Performed This test is done if you have symptoms of a previous infection by group A Streptococcus. Some illnesses caused by this bacteria are: Bacterial endocarditis Glomerulonephritis, a kidney problem Rheumatic fever , which can affect the heart, joints, or bones Scarlet fever Strep throat

The ASO antibody may be found in the blood weeks or months after the strep infection has gone away. Normal Results A negative test result means you have likely not had a recent strep infection. The healthcare provider may repeat the test again in 2 - 4 weeks. Sometimes a test that was first negative will come back positive. Normal value ranges may vary slightly among different laboratories. Talk to your doctor about the meaning of your specific test results. What Abnormal Results Mean An abnormal or positive test means you recently had a strep infection, even if you had no symptoms. The ASO test may stay positive (sometimes called detectable) for 2 to 4 months afterward you are first infected. Risks Veins and arteries vary in size from one patient to another and from one side of the body to the other. Obtaining a blood sample from some people may be more difficult than from others. Other risks associated with having blood drawn are slight but may include:

Excessive bleeding Fainting or feeling light-headed Hematoma (blood accumulating under the skin) Infection (a slight risk any time the skin is broken)

Post-streptococcal glomerulonephritis (GN)

Email this page to a friendShare on facebookShare on twitterBookmark & SharePrinter-friendly version Post-streptococcal glomerulonephritis (GN) is a disorder of the kidneys that occurs after infection with certain strains of Streptococcus bacteria. Causes Post-streptococcal GN is a form of glomerulonephritis. It is caused by an infection with a type of streptococcus bacteria. The infection does not occur in the kidneys, but in a different part of the body, such as the skin or throat. The strep bacterial infection causes the tiny blood vessels in the filtering units of the kidneys (glomeruli) to become inflamed. This makes the kidneys less able to filter the urine. Post-streptococcal GN is uncommon today because infections that can lead to the disorder are commonly treated with antibiotics. The disorder may develop 1 - 2 weeks after an untreated throat infection, or 3 - 4 weeks after a skin infection. It may occur in people of any age, but it most often occurs in children ages 6 - 10. Although skin and throat infections are common in children, post-streptococcal glomerulonephritis is a rare complication of these infections. Risk factors include: Strep throat Streptococcal skin infections (such as impetigo)

Symptoms Decreased urine output Rust-colored urine Swelling (edema) o General swelling o Swelling of the abdomen o Swelling of the face or eyes o Swelling of the feet, ankles, hands Visible blood in the urine

Other symptoms that may occur with this disease: Joint pain

Joint stiffness or swelling

Exams and Tests A physical examination shows swelling (edema), especially in the face. Abnormal sounds may be heard when listening to the heart and lungs with a stethoscope (auscultation). Blood pressure is often high. Other tests that may be done include: Anti-DNase B Kidney biopsy (this is usually not needed) Serum ASO (and streptolysin O) Serum complement levels Urinalysis

Treatment There is no specific treatment for post-streptococcal glomerulonephritis. Treatment is focused on relieving symptoms. Antibiotics, such as penicillin, should be used to destroy any streptococcal bacteria that remain in the body. Blood pressure medications and diuretic medications may be needed to control swelling and high blood pressure. Corticosteroids and other anti-inflammatory medications are generally not effective.

You may need to limit salt in the diet to control swelling and high blood pressure. Outlook (Prognosis) Post-streptococcal glomerulonephritis usually goes away by itself after several weeks to months. In small number of adults, it may get worse and lead to chronic kidney failure. Sometimes it can progress to end-stage kidney disease, which requires dialysis and a kidney transplant. Possible Complications Acute renal failure Chronic glomerulonephritis Chronic renal disease Congestive heart failure or pulmonary edema End-stage renal disease Hyperkalemia High blood pressure (hypertension) Nephrotic syndrome

When to Contact a Medical Professional Call your health care provider if:

You have symptoms of post-streptococcal GN You have post-streptococcal GN, and you have decreased urine output or other new symptoms

Prevention Treating known streptococcal infections may prevent post-streptococcal GN. Alternative Names Glomerulonephritis - post-streptococcal; Post-infectious glomerulonephritis

Background
Acute glomerulonephritis is a disease characterized by the sudden appearance of edema, hematuria, proteinuria, and hypertension. It is a representative disease of acute nephritic syndrome in which inflammation of the glomerulus is manifested by proliferation of cellular elements secondary to an immunologic mechanism (see the following image).[1, 2]

Schematic representation of proposed mechanisms involved in the development of acute poststreptococcal glomerulonephritis (APSGN).MES: mesangial cell; END: endothelial cell; PMN: polymorphonuclear cell; M: macrophage; T: T lymphocyte; GMB: glomerular basement membrane; C: complement; Anti -NAPlr-Ab: Anti-NAPlrantibody.Courtesy of open access article, "The Role of Nephritis-Associated Plasmin Receptor (NAPlr) in Glomerulonephritis Associated with Streptococcal Infection." Oda T, Yoshizawa N, Yamakami K, et al. Journal of Biomedicine and Biotechnology, 2012; doi: 10.1155/417675.

Acute poststreptococcal glomerulonephritis (APSGN) results from an antecedent infection of the skin (impetigo) or throat (pharyngitis) caused by nephritogenic strains of group A beta-hemolytic streptococci.[3, 4, 5] The concept of nephritogenic streptococci was initially advanced by Seegal and Earl in 1941, who noted that rheumatic fever and acute poststreptococcal glomerulonephritis (both nonsuppurative complications of streptococcal infections) did not simultaneously occur in the same patient and differ in geographic location.[6] Acute poststreptococcal glomerulonephritis occurs predominantly in males and often completely heals, whereas patients with rheumatic fever often experience relapsing attacks. The M and T proteins in the bacterial wall have been used for characterizing streptococci. Nephritogenicity is mainly restricted to certain M protein serotypes (ie, 1, 2, 4, 12, 18, 25, 49, 55, 57, and 60) that have shown nephritogenic potential. These may cause skin or throat infections, but specific M types, such as 49, 55, 57, and 60, are most commonly associated with skin infections. However, not all strains of a nephritis-associated M protein serotype are nephritogenic.[7] In addition, many M protein serotypes do not confer lifetime immunity. Group C streptococci have been responsible for recent epidemics of APSGN (eg,Streptococcus zooepidemicus). Thus, it is possible that nephritogenic antigens are present and possibly shared by streptococci from several groups.[2] In addition, nontypeable group A streptococci are frequently isolated from the skin or throat of patients with glomerulonephritis, representing presumably unclassified nephritogenic strains. [7] The overall risk of developing acute poststreptococcal glomerulonephritis after infection by these nephritogenic strains is about 15%. The risk of nephritis may also be related to the M type and the site of infection. The risk of developing nephritis infection by M type 49 is 5% if it is present in the throat. This risk increases to 25% if infection by the same organism in the skin is present. See also Acute Glomerulonephritis, Emergent Management of Acute Glomerulonephritis, and Rheumatic Heart Disease.

Pathophysiology
Most forms of acute poststreptococcal glomerulonephritis (APSGN) are mediated by an immunologic process. Cellular and humoral immunity is important in the pathogenesis of this disease, and humoral immunity particularly in APSGN. Nonetheless, the exact mechanism by which APSGN occurs remains to

be determined. The 2 most widely proposed theories include (1) glomerular trapping of circulating immune complexes and (2) in situ immune antigen-antibody complex formation resulting from antibodies reacting with either streptococcal components deposited in the glomerulus or with components of the glomerulus itself, which has been termed molecular mimicry. Additional evidence has also been presented to support the anti-immunoglobulin activity or glomerular plasmin-binding activity of streptococcal antigens. The cross-reactivity of streptococci and mammalian tissue implicating molecular mimicry in acute rheumatic fever led to evidence of a similar mechanism involved in APSGN. However, the similar cross-reactivity patterns of rheumatogenic and nephritogenic strains of streptococci argue against molecular mimicry involving M proteins.

Immune complex-mediated mechanisms

An immune complexmediated mechanism is the most widely proposed mechanism leading to the development of APSGN. Nephritogenic streptococci produce proteins with unique antigenic determinants. These antigenic determinants have a particular affinity for sites within the normal glomerulus. Following release into the circulation, the antigens bind to these sites within the glomerulus. Once bound to the glomerulus, they activate complement directly by interaction with properdin. Glomerular-bound streptococcal antibodies also serve as fixed antigens and bind to circulating antistreptococcal antibodies, forming immune complexes. Complement fixation via the classic pathway leads to the generation of additional inflammatory mediators and recruitment of inflammatory cells. Zymogen (NSAP) and NAPlr Two major antigens have presently been identified as the potential cause(s) of APSGN: A zymogen precursor of exotoxin B (SPEB [streptococcal pyrogenic toxin B]) or nephritis strainassociated protein (NSAP), and nephritis-associated plasmin receptor (NAPlr), a glycolytic enzyme, which has glyceraldehydes-3-phosphate dehydrogenase (GAPDH) activity with plasmin-binding capacity, a nephritogenic property that aids in circulating immune complex deposition.[8, 9, 10, 11, 12] NSAP is a 46- to 47-kd protein that is unique to the extracellular products of nephritogenic streptococci. NSAP was demonstrated in glomerular deposits of 14 of 21 patients with APSGN, but none in control biopsy samples from 5 patients with acute kidney injury and 11 with nonstreptococcal glomerulonephritis. NSAP was also detected in serum from 96% of APSGN patients compared with 15-20% of patients with either acute kidney injury or impetigo.[13] NSAP has antigenic, biochemical, and structural similarities to streptokinase from group C streptococcal organisms, binds to plasmin, and is a plasminogen activator. However, streptokinase cannot be demonstrated in glomerular deposits for patients with APSGN, and serum levels of purified group A streptokinase were similar in patients with APSGN and those with acute kidney injury. Thus, although NSAP and streptokinase have similarities, they appear to be 2 distinct proteins.[13] Yoshizawa et all isolated a 43-kd protein called preabsorbing antigen (PA-Ag) that is putatively identical to endostreptosin.[14, 15] PA-Ag has the ability to preabsorb the antibody in convalescent sera from patients with APSGN and thus prevent its deposition in glomeruli. PA-Ag activates the alternative pathway.[15] This 43-kd protein was later identified by Yamakami et al as NAPlr.[16] These researchers noted that NAPlr was present in 100% of the early biopsy samples from in glomeruli of patients with APSGN.[17] The glomerular distribution of NAPlr deposition and plasmin activity determined by in situ zymography are identical. The fact that NAPlr did not co-localize with C3 in glomerular deposits suggests that: (1) complement was activated by NAPlr in the circulation rather than in situ, and (2) NAPlr induced APSGN independently of complement activation by binding to the glomerular basement membrane (GBM) and mesangial matrix via its adhesive character, subsequently trapping and activating plasmin and causing in situ glomerular damage by degrading the GBM or activating latent matrix metalloproteases.[17, 18] SPEP is another group A streptococcal nephrogenic antigen most often isolated in Latin America, the United States, and Europe. It is a cationic protease with plasmin-binding properties. It localizes to

glomeruli in patients with APSGN and is secreted as an exotoxin. Corresponding serum anti-SPEP antibodies occur in most patients during convalescence. SPEP titers correlate better with nephritis than either ASOT or anti-DNase B antibodies. A proposed mechanism for acute poststreptococcal glomerulonephritis is that soluble, released NAPlr binds to glomeruli and provide a mechanism to capture plasmin activated by streptokinase. The activated plasmin bound to NAPlr associates with the GBM and mesangium. Both NAPlr and NSAP are capable of inducing chemotactic (monocyte chemoattractant protein 1) and interleukin (IL) 6 moieties in mesangial cells, promoting enhanced expression of adhesion molecules. Peripheral blood leukocytes also release other cytokines such as tumor necrosis factor-alpha, IL-8, and transforming growth factor-beta, which react with NSAP. These findings highlight the inflammatory potential of these nephritogenic antigens. [19, 20,
21, 22]

Bound plasmin can cause tissue destruction by direct action on the glomerular basement membrane or by indirect activation of procollagenases and other matrix metalloproteinases (MMPs). NAPlr can also activate the alternate complement pathway, leading to accumulation of polymorphonuclear cells and macrophages and local inflammation. In addition, the in situ formed and circulating immune complexes can readily pass through the altered glomerular basement membrane and accumulate on the subepithelial space as humps. Complement activation from both serum profiles and immunofluorescence patterns for glomerular deposits indicates that C3 activation in APSGN is predominantly via the alternative pathway. [23, 24, 25] The immune deposits consist of immunoglobulin G (IgG), C3, properdin, and C5.[25] These deposits rarely contain C1q or C4, both components of the classic complement pathway. A recent study also showed evidence for activation of the lectin-binding pathway from deposition of membrane-bound lipoprotein in some patients with APSGN.[26] During the early phase of the diseases (first 2 wk), evidence of classical pathway activation is seen, as demonstrated by transient depression of serum C1q, C2, and/or C4 concentrations. [27, 28, 29] and the presence of circulating C1-inhibitor-C1r-C1s complexes or C4d fragments. It is proposed that the circulating immune complexes in the acute stage of the disease due to classic complement pathway activation is distinct from that seen in the glomerular immune deposits. APSGN with typical findings on histopathology may occur in patients with no evidence of complement activation, as manifested by depression of serum C3 concentrations.[30, 31] Hypocomplementemic patients differ from normocomplementemic patients by virtue of the presence of factor B in the glomerular deposits and the absence of factor H, which is a regulatory protein of the alternative pathway.[25] These findings suggest that the glomerular immune deposits of C3bBb convertase may be due to ongoing complement activation in situ rather than systemic activation. Crescentic APSGN may have an increased association with normocomplementemia. The reason for this possible association of normocomplementemia with crescent formation in APSGN is not clear. Serum IgG levels are elevated in about 44% of patients with APSGN.[32] Less than 50% of patients with elevated serum IgG levels, however, have glomerular deposits of IgG. Elevated IgG levels were more likely to be found in patients with antistreptolysin O titers of greater than or equal to 833 Todd units ( P < .001). However, elevated serum IgG concentrations do not correlate with severity of disease, age of the patient, or serum albumin or C3 levels. It would appear that failure to form antibody to a glomerular-bound protein produced by nephritogenicStreptococcus, is thought to be the origin of the IgG in glomerular deposits, is in some way significantly associated with elevated serum levels of IgG and antibody to streptolysin O.[32] There is considerable evidence both for and against most putative nephritogenic antigens. Genomic sequencing of nephritogenic strains of streptococci may lead to the discovery of new nephritogenic antigen candidates in conserved and differing regions of the streptococcal genome. This will lead to improved understanding of the pathogenetic mechanism(s) leading to the development of APSGN.

Nonimmune complex-mediated mechanisms

Other nonimmune complex mediated mechanisms have been proposed for the development of APSGN, such as delayed-type hypersensitivity, superantigens, and autoimmune phenomena. A role for delayed-type hypersensitivity has been implicated in the pathogenesis of this disease. Early in the course of APSGN, resident endothelial and mesangial cells are predominantly proliferated, and this is accompanied by infiltration with polymorphonuclear leukocytes and monocytes. Macrophages are effector cells that cause resident cellular proliferation. The infiltration of macrophages in the glomeruli is mediated by complement-induced chemotaxis and, most likely, by an antigen-specific event related to delayed-type hypersensitivity mediated by helper/inducer T cells. Streptococcal M proteins and pyrogenic exotoxins can act as superantigens. These cause a marked expansion of T cells expressing specific T-cell receptor B-chain variable gene segments. Massive T-cell activation occurs, with release of T-cellderived lymphokines such as IL-1 and IL-6. Autologous IgG in APSGN becomes antigenic and elicits an anti-IgG rheumatoid factor response, leading to formation of cryoglobulins. Cryoglobulins, rheumatoid factors, and other autoimmune phenomena occur in APSGN and are thought to play a role in the pathogenesis of the disease together with streptococcal superantigens.

Epidemiology
Currently, approximately a quarter of APSGN is due to Streptococcus. In developed countries such as the United States, APSGN more commonly affects elderly persons, with diabetes mellitus, malignancy, alcoholism, human immunodeficiency virus infection, and intravenous drug use being risk factors. The disease affects white males more frequently, often around the fifth decade of life. Over the last 2-3 decades, the incidence of acute poststreptococcal glomerulonephritis (APSGN) has declined in the United States as well as in other countries, such as Japan, Central Europe, and Great Britain. The estimated worldwide burden of APSGN is approximately 472,000 cases per year, with approximately 404,000 cases being reported in children and 456,000 cases occurring in less developed countries.[33] APSGN associated with skin infections is most common in tropical areas where pyoderma is endemic, whilst pharyngitis-associated APSGN predominates in temperate climates.[33] However, in recent years, a slight increase in the incidence of the disease has been reported, although the actual incidence is still unknown. This is particularly true in elderly persons, especially in association with debilitating conditions such as alcoholism or intravenous drug abuse.[34] The overall decline in APSGN may be due to the improvement in living conditions with less crowding. However, other factors, including decreased prevalence or infectivity of the nephritogenic streptococci, may also have contributed to the decline in incidence. The recently observed increase in incidence is more difficult to explain. In the past 30 years, large epidemics have been reported in middle-income countries, with clusters of cases in more developed countries.[35] However, in poorly developed countries, it is likely that clusters of cases of APSGN may go underreported. Globally, as many as 50% of cases may be subclinical, although it is known that APSGN continues to have a wide distribution. A high percentage of affected persons have mild disease and are asymptomatic (estimates of the ratio of asymptomatic to symptomatic patients vary from 2:1 to 3:1); thus, the actual incidence of the disease is not known. In developing countries APSGN, usually occurs in children, predominately males and often as epidemics. APSGN usually occurs as sporadic cases, but epidemic outbreaks have taken place in communities with densely populated dwellings that have poor hygienic conditions with a high incidence of malnutrition, anemia, and intestinal parasites. In certain regions, epidemics may occur in cyclical outbreaks every 5-7 years for unknown reasons. A strong seasonal variation is also noted; sporadic APSGN following upper respiratory tract infection, pharyngitis, and tonsillitis is more common in winter and spring in temperate areas, whereas skin

infections are commonly found to precede APSGN in the more tropical and subtropical areas, with a peak incidence during summer and autumn.

Age-, race-, and sex-related demographics

The disease is more frequent in children aged 2-12 years, with a peak prevalence in individuals aged approximately 5-6 years,[36] although it has been reported in infants as young as 1 year and in adults as old as 90 years. However, in most large series, 5-10% of patients are older than 40 years, and 5% are younger than 2 years. The most commonly affected age group is those aged 5-20 years, although in the developed world, the disease is mostly seen in white males, around the fifth decade of life. Although a male predominance is noted in symptomatic cases (male-to-female ratio, 1.7-2:1) for unknown reasons (APSGN is seen predominantly in males), when subclinical and clinical disease is taken into account, the rates are the same in males and females. No racial predilection is noted for acute poststreptococcal glomerulonephritis; the condition is reported in all ethnic and cultural groups. In urban populations, a predilection toward minority populations is observed; however, this may be related more to the socioeconomic factor of overcrowding than to any racial predilection. In the developed world, APSGN affects mainly elderly white males, more frequently around the fifth decade of life. In the developing world, the disease is seen mainly in black children, predominantly males.

Prognosis
The course and prognosis for acute poststreptococcal glomerulonephritis (APSGN) is well known and almost always favorable in children, but this is not so with nonstreptococcal forms of the condition. In addition, for unknown reasons, the prognosis for individuals with APSGN is not as good for adults (particularly elderly persons) as it appears to be for children. In elderly patients with debilitating conditions (eg, malnutrition, alcoholism, diabetes, chronic illness), the incidences of azotemia (60%), congestive heart failure (40%), and nephrotic-range proteinuria (20%) are high. Death may occur in 20-25% of these patients.[37, 38] Prolonged follow-up observation appears to be indicated. The ultimate prognosis in individuals with APSGN largely depends on the severity of the initial insult. Epidemic poststreptococcal acute glomerulonephritis appears to end in virtually complete resolution and healing in all patients, and the prognosis is favorable for 95% of children with acute sporadic poststreptococcal glomerulonephritis. The prognosis for persons with acute glomerulonephritis secondary to other causes is less certain. Edema usually resolves within 5-10 days, and the blood pressure usually returns to normal after 2-3 weeks, even though persistence of elevated pressures for as many as 6 weeks is compatible with complete resolution. Urinary abnormalities resolve at various times after onset. Proteinuria may disappear within the first 2-3 months or may slowly decrease over 6 months. Intermittent or postural proteinuria has been noted for 1-2 years after onset. Gross hematuria usually disappears within 1-3 weeks but may be exacerbated by physical activity. C3 concentration returns to normal in more than 95% of patients by the end of 8-10 weeks. Microscopic hematuria usually disappears after 6 months, but its presence for as long as 1 year should not cause undue concern, and even more prolonged hematuria (1-3 y) has been observed in some patients who ultimately have demonstrated complete resolution of their renal disease. Strongly consider the possibility of chronic renal disease when both hematuria and proteinuria persist longer than 12 months. In a few hospitalized patients, the initial injury is so severe that either persistent renal failure or progressive renal failure ensues. However, histologic regression of the disease in most patients is predictable, and the ultimate prognosis is good. Although clinical resolution occurs in most patients, several authors report time-related reduction in precise measurements of renal function, as well as diminished renal functional reserve. These studies

further support the thesis that any significant loss of nephrons leads to hyperfiltration of the remaining units. Studies that have followed up children with APSGN for 10-20 years have shown that approximately 20% of the patients have abnormal urine analyses, with less than 1% having azotemia. [39] Clinical manifestations of the disease rarely recur after the first 3 months, and second episodes of acute glomerulonephritis are rare.

Complications
The most common acute complication is hypertension with or without central nervous system (CNS) manifestations. Anemia is common early in the disease and is primarily due to dilution, although in 2 instances, autoimmune hemolytic anaemia was documented in the early stages of APSGN. [40, 41] Anemia tends to resolve with diuresis. A few patients may have diminished erythropoiesis in the recovery phase and have some persisting anemia. An occasional patient develops pulmonary edema because of the marked increase in vascular volume that is present in the early phase of the disease. Congestive heart failure is rare but has been reported. Definite myocarditis has also been documented. In most patients with moderate to severe APSGN, a measurable reduction in volume of glomerular filtrate (GF) is present, and the capacity to excrete salt and water is usually diminished, leading to expansion of the extracellular fluid (ECF) volume. The expanded ECF volume is responsible for edema and, in part, for hypertension, anemia, circulatory congestion, and encephalopathy. Persistence or worsening of azotemia is always troubling and may suggest acute kidney injury. The presence of acute kidney injury may suggest an alternate diagnosis (eg, membranoproliferative glomerulonephritis [MPGN], HenochSchnlein purpura [HSP], systemic lupus erythematosus [SLE]) or a severe or worsening APSGN, such as observed in those with crescentic glomerulonephritis or rapidly progressive glomerulonephritis. [42] The renal survival of APSGN in the developed world is significantly worse than in the epidemic form of APSGN seen in the developing world. A third to two third of patients in the developed world develop chronic kidney disease that may progress to end-stage kidney disease. These outcomes may be influenced by the susceptibility of patients in developed countries, who are usually old and have comorbidities.

Patient Education
Clearly and specifically explain the nature of the disease, its course, and the eventual prognosis of the condition to the child (if old enough to understand) and the parents and/or caregivers. They need to understand that, although complete resolution is expected, a small possibility exists for persistent disease, and that an even smaller possibility exists for progression. This information is necessary for some patients to ensure that compliance with the follow-up program occurs. Clearly outline a follow-up plan and discuss the plan with the family. Blood pressure measurements and urine examinations for protein and blood constitute the basis of the follow-up plan. Perform examinations at 4- to 6-week intervals for the first 6 months and at 3- to 6-month intervals thereafter, until both hematuria and proteinuria have been absent and the blood pressure has been normal for 1 year. Documenting that the low C3 has returned to normal after 8-10 weeks may be useful. For patient education information, see High Blood Pressure Center, as well asBlood in the Urine and Chronic Kidney Disease.

History and Physical Assessment

A delay in the diagnosis of acute poststreptococcal glomerulonephritis (APSGN) is sometimes related to the absence of a clear history of a preceding documented streptococcal infections. [43] This may be due to more stringent definition criteria that require documented evidence of past infection by streptococci. Typically, an acute nephritic syndrome develops 1-2 weeks after an antecedent streptococcal pharyngitis, whereas a lapse of 3-6 weeks is common before a nephritic syndrome develops following streptococcal pyoderma. Other factors contributing to a delay in the diagnosis of acute poststreptococcal glomerulonephritis include the sporadic occurrence of disease, because this often requires a high index of suspicion, as opposed to epidemics; the history of an upper respiratory tract infection alone during the preceding month, which may not be diagnostically helpful, because upper respiratory tract infections are common during winter; the misdiagnosis of severe volume overload in a child as primarily due to a cardiac cause, because volume overload in children is relatively rare; and the absence of visible hematuria (a presentation that is relatively common). Physicians must consider the possibility of acute poststreptococcal glomerulonephritis in children with symptoms that may be secondary to hypertension or congestive heart failure, even in the absence of visible hematuria or a history of a preceding streptococcal infection. Most patients with acute glomerulonephritis exhibit milder symptoms and/or signs somewhere between the extremes described below.

Asymptomatic versus symptomatic presentation

At one extreme is the asymptomatic child whose disease is discovered only by examination of the urine. Based on surveillance studies of the siblings and/or household contacts of children affected with acute poststreptococcal glomerulonephritis (APSGN), at least 50% of persons with laboratory evidence of nephritis (ie, abnormal urinalysis) appear to have no symptoms or signs of clinical illness. At the other extreme is the child who presents with severe disease manifested by oliguria, edema, hypertension, and azotemia and with proteinuria, hematuria, and urinary casts (cylindruria).

Typical postinfectious presentation

In those patients whose acute glomerulonephritis is the result of a postinfectious cause (ie, poststreptococcal acute glomerulonephritis being the most common), a latent period of 7-21 days between onset of the streptococcal infection and development of clinical glomerulonephritis is characteristic.[44] This latent period, more clearly defined after pharyngeal infections than after pyoderma, averages approximately 10 days. Almost characteristic by their absence are arthralgia, arthritis, carditis, hepatic involvement, and gastrointestinal bleeding. Pallor is common at onset and is not explained entirely by the presence of anemia. The median age of presentation in childhood is age 6-8 years, with the condition being extremely rare prior to age 2 years.[45, 46, 47, 48, 49] In very young children, it is postulated that APSGN is rare because of the low rate of streptococcal pharyngitis in this age group and an immature immune response.[48] Males are 2 times more likely to have this condition compared with females; the reason this difference in sex prevalence is not known.[45, 48, 49] However, the site of streptococcal infection (pyoderma or pharyngitis) does not influence the sex difference. Edema and/or hematuria Edema and/or gross hematuria represent the most common clinical presentation resulting in patients seeking medical attention. One or both findings usually appear abruptly and may be associated with various degrees of malaise, lethargy, anorexia, fever, abdominal pain, and headache. The classic description of tea- or cola-colored urine occurs in approximately 25-60% of patients.

Edema is the most frequent and sometimes the only clinical finding. According to some investigators, edema is found in approximately 85% of patients. Edema usually appears abruptly and first involves the periorbital area, but it may be generalized. The degree of edema widely varies and depends on a number of factors, including the severity of glomerular involvement, the fluid intake, and the degree of hypoalbuminemia. The triad of edema, hematuria, and hypertension is classic for APSGN. Three phases of the disease can be identified: the latent phase, the acute phase, and the recovery phase. Gross hematuria occurs at onset in 30-50% of children with poststreptococcal acute glomerulonephritis who require hospitalization. The urine is usually described as being smoky, cola colored, tea colored, or rusty. The color is usually dependent on the amount of blood present and the pH of the urine. Observant parents may note oliguria. Clots are exceedingly rare in persons with acute glomerulonephritis. Proteinuria Varying degrees of proteinuria are also typically present, but nephrotic syndrome is rare, occurring in 24% of cases.[45] . Both microscopic proteinuria and mild proteinuria may persist for several months after the acute presentation. Hypertension Hypertension is the third cardinal feature of poststreptococcal acute glomerulonephritis and is reported in 50-90% of children who are hospitalized with acute glomerulonephritis. The magnitude of the increase in blood pressure widely varies; however, systolic pressures greater than 200 mm Hg and diastolic pressures greater than 120 mm Hg are not unusual. Hypertension usually resolves in 1-2 weeks and rarely requires long-term treatment.[50, 51] Hypertensive encephalopathy Hypertensive encephalopathy can be the presenting feature of postinfectious glomerulonephritis. This condition has been reported in approximately 5% of hospitalized children and is the most serious early complication of this disease. In these patients, hypertension is usually severe and is accompanied by signs of central nervous system (CNS) dysfunction such as headache, vomiting, depressed sensorium, confusion, visual disturbances, aphasia, memory loss, coma, and convulsions. The mechanism of hypertension is most likely retention of sodium and water with resulting expansion of the extracellular space.[50] Hypertensive encephalopathy has been reported in the occasional individual with minimal or no edema and with minimal urinary abnormalities. Since the urinalysis in such patients exhibits minimal abnormalities, the underlying cause may not be readily apparent. A high index of suspicion is required to make an appropriate diagnosis. Circulatory congestion Circulatory congestion is apparent in most children admitted to the hospital but is responsible only rarely for significant early symptoms. Dyspnea, orthopnea, and cough may be present. Both systolic and diastolic hypertension may be present to a varying degree. Either bradycardia or tachycardia may be observed. Pulmonary rales are often audible. At times, the only evidence of congestion is detected on chest radiograph. A prominent cardiac shadow may be present until the onset of diuresis. In the patient with an otherwise normal cardiovascular system, cardiac failure is unusual.

Uncommon/atypical presentation suggesting alternative diagnosis

The development of clinical nephritis (ie, hematuria and/or edema) either during or within 2-5 days after the onset of a respiratory tract infection is atypical and suggests the possibility of some other form of glomerulonephritis. Subclinical cases may be missed and are sometimes identified based on knowledge of the affected family or contacts. One report found APSGN in 20% of asymptomatic family members with the condition.[34, 52] Numerous case reports describe children who present with extreme manifestations,

usually hypertensive encephalopathy, who do not display the typical urinary findings at presentation.[53] Serial examination of the urine after presentation may eventually confirm the suspicion of acute glomerulonephritis. An insidious onset of edema is more indicative of other forms of renal disease. An occasional child may have a scarlatiniform rash or evidence of a viral exanthema, but petechial or purpuric rashes suggest other conditions.

Typical physical findings

The most frequent findings on clinical examination are features of an acute nephritic syndrome such as edema with mild hypertension, and there may be evidence of healed or healing impetigo. Urine dipsticks analysis usually shows blood and mild proteinuria. Hematuria is rarely gross, and nephrotic-range proteinuria is seen in 5-10% of cases. Red blood cells casts are detected in urine sediment. Often, patients have oliguria that resolves within a week. Microscopic hematuria and mild proteinuria may persist for several months after the acute presentation. In cases complicated by acute kidney injury or hypertensive crises, the physical findings vary with the severity of the complications seen. See Differentials.

Diagnostic Considerations
In the evaluation of a patient with acute glomerulonephritis, if evidence of a previous streptococcal infection is missing or inconclusive, then a search for another infectious cause appears appropriate. See also Acute Glomerulonephritis and Emergent Management of Acute Glomerulonephritis. Bacterial and viral infections The syndrome of acute glomerulonephritis has been reported following many other bacterial illnesses (eg,Streptococcus pneumoniae, Staphylococcus aureus and S epidermidis, Rickettsia rickettsiae, Mycoplasmaspecies, Meningococcus species, Leptospira species). In addition, certain viral illnesses have preceded the onset of fairly typical acute glomerulonephritis; among the most common are varicellazoster virus (VZV), cytomegalovirus (CMV), and the Epstein-Barr virus (EBV). IgA-associated glomerulonephritis Immunoglobulin A (IgA)associated glomerulonephritis may be confused with acute poststreptococcal glomerulonephritis.[4, 18, 42, 54] In the form of IgA nephropathy associated with a typical anaphylactoid purpura (ie, Henoch-Schnlein purpura nephritis), the characteristic rash and the associated symptoms of either abdominal pain or arthritis and/or arthralgia help in the differentiation; however, in atypical cases, marked similarity may be present. All of the clinical manifestations of APSGN have been reported in persons with Henoch-Schnlein purpura nephritis, although significant hypertension and edema are found less commonly in individuals with Henoch-Schnlein purpura than in those with APSGN. In addition, evidence of a previous streptococcal illness is usually lacking in individuals with Henoch-Schnlein purpura nephritis, and complement values (C3 and/or C4) are usually normal. Urticarial or purpuric rashes, abdominal complaints, and arthritis and/or arthralgia are found almost exclusively in persons with Henoch-Schnlein purpura. Berger disease or IgA nephropathy usually presents as an episode of gross hematuria occurring during the early stages of a respiratory illness; no latent period occurs, and hypertension or edema is uncommon. Recurrent episodes of gross hematuria, associated with respiratory illnesses, followed by persistent microscopic hematuria, are highly suggestive of IgA nephropathy. In contrast, acute poststreptococcal glomerulonephritis usually does not recur, and second episodes are rare. MPGN Mesangiocapillary or membranoproliferative glomerulonephritis (MPGN) may have a presentation that is virtually identical to that of poststreptococcal acute glomerulonephritis. The initial manifestations are often more serious in persons with MPGN than in those with IgA nephropathy; the renal function is reduced markedly (ie, large elevation of serum creatinine). Evidence of preexisting streptococcal infection is absent, although cases of MPGN have been reported in which clear evidence of such an infection is present. In most cases, C3 levels are depressed persistently, longer than 6 weeks. Urinary abnormalities persist past the time of expected resolution for acute poststreptococcal glomerulonephritis. Crescentic glomerulonephritis Crescentic glomerulonephritis is the term used to describe a histologic picture of severe proliferative glomerulonephritis. In persons with crescentic glomerulonephritis, in addition to inflammatory changes

within the glomerular tuft, extensive proliferation exists within the Bowman space, leading to the formation of synechiae between the glomerular tuft and Bowman capsule.[42] The clinical picture is generally referred to as rapidly progressive glomerulonephritis and may be secondary to numerous causes, including an immune-complex mediated poststreptococcal nephritis. The initial clinical picture is generally severe, and resolution appears delayed. Other types of glomerulonephritis Other forms of glomerulonephritis (eg, systemic lupus erythematosus nephritis, familial nephritis, chronic glomerulonephritis) may occasionally be confused with acute poststreptococcal glomerulonephritis when an acute exacerbation of the previously present nephropathy is present. In addition to the lack of expected complete resolution, other features suggest a condition other than acute poststreptococcal glomerulonephritis. See Hemolytic Complement under Workup for the differential diagnosis of acute glomerulonephritis according to C3 levels.

Differential Diagnoses
Crescentic Glomerulonephritis Diffuse Proliferative Glomerulonephritis Endocarditis-associated glomerulonephritis Hematuria IgA Nephropathy Membranoproliferative Glomerulonephritis Membranoproliferative Glomerulonephritis Nephritis Shunt nephritis

Approach Considerations
As noted earlier, consider the possibility of acute poststreptococcal glomerulonephritis (ASPGN) in children with symptoms that may be secondary to hypertension or congestive heart failure, even in the absence of visible hematuria or a history of a preceding streptococcal infection. A urinalysis is helpful as microscopic hematuria is typically present in children with APSGN.

Streptococcal antibodies
Recent poststreptococcal infection is most commonly demonstrated by serological markers for elevated antibodies to extracellular streptococcal antigens. The streptozyme test, which measures 5 different streptococcal antibodies, is positive in more than 95% of patients with APSGN due to pharyngitis. However, sensitivity drops to 80% if APSGN follows pyoderma. The streptococcal antibodies measured include the following: Antistreptolysin (ASO) Antihyaluronidase (AHase) Antistreptokinase (ASKase) Antinicotinamide-adenine dinucleotidase (anti-NAD) Anti-DNAse B antibodies Apart from antistreptokinase (ASKase), all other streptococcal antibodies are commonly elevated after a pharyngitis, whereas only anti-DNAase B and AHase titers are typically increased after pyoderma. Thus, if only an ASO titer is used to screen for APSGN after skin infections, it may be falsely low or negative, and if the patient has received prior antibiotic treatment for a pharyngitis, this may blunt the rise in ASO titer.

Complement profiles
Theoretically, the complement (or C3) levels should be decreased in all such patients; however, the duration of low values may be quite brief and, therefore, missed, even when examined serially. When the serum level is low in individuals with APSGN, a depressed level for longer than 6-8 weeks is unusual. Thus, if the value remains low after this period of time, thinking of some other nephritic process, such as membranoproliferative glomerulonephritis (MPGN), is wise.

Kidney biopsy
Kidney biopsy is generally not recommended in the evaluation of patients with APSGN since the clinical history is usually highly suggestive and resolution of APSGN typically begins within 1 week of presentation. However, the performance of a renal biopsy is indicated in patients whose clinical presentation, laboratory findings, or disease course is atypical. In such persons, study of the histology by light, immunofluorescent, and electron microscopy may be diagnostic. Indications for kidney biopsy include the following: Failure to document a recent streptococcal infection by a rise in ASO or streptozyme titer Normocomplementemia Renal insufficiency, especially if the glomerular filtration rate remains less than 30 mL/min/1.73 m 2 for more than 1 week Persistently low complement (C3) levels beyond 6-8 weeks, without resolution of features of acute glomerulonephritis. Recurrent episodes of hematuria, especially frank hematuria The typical light microscopy findings are that of diffuse hypercellularity of endothelial and mesangial cells and infiltration of the glomerular tuft with polymorphonuclear cells.[55] In more severe cases, epithelial crescents may form during the course of APSGN. In a small percentage of patients, crescentic involvement may be present in over 50% of glomeruli, leading to the clinical picture of rapidly progressive glomerulonephritis.[56, 57, 58] Immunofluorescence performed on biopsy specimens taken during the acute phase of the illness shows discrete granular deposits of IgG and C3 in a capillary loop and mesangial distribution [59, 60] However, IgG

deposits may be absent in about a third of biopsy samples. The presence of heavy and sometimes confluent capillary loop deposits with the total absence of mesangial deposits leads to the starry-sky appearance described in these biopsy reports. The presence of subepithelial humps on electron microscopy is the hallmark finding in biopsy specimens from patients with APSGN. These electron-dense deposits may also occur in subendothelial and intramembranous locations.

Imaging studies
No specific radiologic studies are particularly helpful in either the evaluation or the treatment of patients with APSGN. Renal ultrasonography generally demonstrates normal to slightly enlarged kidneys bilaterally with some evidence of increased echogenicity, and chest radiographs commonly demonstrate central venous congestion in a hilar pattern, the degree of which parallels the increase in extracellular fluid volume. Occasionally, an enlarged cardiac shadow is evident.

Hematologic and Blood Chemistry Studies

Erythropoiesis may decline in the aftermath of acute glomerulonephritis, particularly in individuals with severe cases. A mild anemia (normocytic, normochromic) is common in persons in the early phase of acute glomerulonephritis; its degree tends to parallel the degree of extracellular fluid (ECF) volume expansion. White blood cell (WBC) and platelet counts are usually normal, although an occasional patient exhibits a leukocytosis; rarely, a mild thrombocytopenia may be present. The extent of renal functional impairment is correlated directly to the severity of the glomerular injury. A few patients have hypoproteinemia and hyperlipidemia. A nephrotic picture has been reported in approximately 5% of hospitalized patients with poststreptococcal acute glomerulonephritis (APSGN). The elevation in the serum concentrations of creatinine and blood urea nitrogen (BUN) is usually modest, although some patients may have severe azotemia at onset. The electrolyte profile is usually normal; hyperkalemia and metabolic acidosis are only present in patients with significant renal functional impairment. The same applies to hyperphosphatemia. Total serum calcium, but not ionized calcium levels, may be low in patients who have a nephrotic picture.

Urine Studies
Urine output is most often reduced in acute glomerulonephritis, and the urine is concentrated and acidic. Glucosuria occurs occasionally, and proteinuria is commonly present. Proteinuria rarely exceeds 3+ by dipstick, corresponding to fewer than 2 g/m 2/d when assessed quantitatively. Approximately 2-5% of children with acute poststreptococcal glomerulonephritis (APSGN) have massive proteinuria and a nephrotic picture. Hematuria is the most consistent urinary abnormality, although histologic findings consistent with acute poststreptococcal glomerulonephritis (APSGN) have been reported in children who had no or minimal urinary abnormalities. Polymorphonuclear leukocytes and renal epithelial cells are common in the urine of patients with poststreptococcal acute glomerulonephritis, particularly during the early phase of the disease. In addition, hyaline and/or cellular casts are almost always present. Red blood cell casts have been found in 60-85% of hospitalized children with APSGN. These casts, although characteristic of a glomerular lesion, are often not detected, because the urine is not fresh or is examined by an inexperienced person.

Streptococcal Studies

Look for evidence of streptococcal infection in all patients. Cultures from either the pharynx or skin may be positive; however, high streptococcal antibody titers are more compelling. Numerous laboratory tests can be used to measure antibodies to various streptococcal antigens (eg, antistreptolysin O [ASO], antihyaluronidase [AH], anti-DNase B) or to combinations of antigens (eg, streptozyme test). Whichever test is used, a rise in the titer of the antibody, measured at an interval of 2-3 weeks, is more meaningful than a single measurement. An ASO titer of 250 U or higher is highly suggestive of recent streptococcal infection.

Hemolytic Complement Levels

Total hemolytic complement and some of its components are low during acute poststreptococcal glomerulonephritis (APSGN). The concentration of C3 has been found to be decreased in more than 90% of patients with this disease when measured serially during the first 2 weeks of the illness. Total hemolytic complement values are also depressed. These tests help to differentiate poststreptococcal from other postinfectious forms of acute glomerulonephritis. The complement levels generally return to normal by 6-8 weeks after onset.

C3 levels
The differential diagnosis of acute glomerulonephritis can be divided as follows (percentages indicate approximate frequency of C3 or hemolytic complement).[61] Low serum complement level may indicate the following systemic diseases: Systemic lupus erythematosus (SLE) (focal, 75%; diffuse, 90%) Subacute bacterial endocarditis (90%) Visceral abscess "Shunt" nephritis (90%) Cryoglobulinemia (58%) Low serum complement level may indicate the following renal diseases: Acute postinfectious glomerulonephritis (>90%) MPGN: Type I (50-80%), type 2 (80-90%) A normal serum complement level may indicate the following systemic diseases: Polyarteritis nodosa group Hypersensitivity vasculitis Wegener granulomatosis Henoch-Schnlein purpura Goodpasture syndrome A normal serum complement level may indicate the following renal diseases: Immunoglobulin (Ig) A (or IgG-IgA) nephropathy Idiopathic rapidly progressive glomerulonephritis (RPGN) Anti-glomerular basement membrane (GBM) disease Negative immunofluorescence findings Immune complex disease

C4 and C5 levels
C4 levels are most often normal. Serum levels of fifth component of complement (C5) and properdin are usually decreased.

Histology
Renal biopsy is not usually indicated in the person who presents with relatively typical acute poststreptococcal glomerulonephritis (APSGN). However, in individuals whose initial presentation or early

course is atypical, an examination of renal tissue may be indicated. Irrespective of the degree of severity of the initial inflammatory response, the histologic picture is consistent and specific. Histologic findings depend on the etiology of the acute glomerulonephritis, the severity of the inflammatory process, and the stage of the disease at the time of the biopsy. This section concentrates on the findings observed in individuals with poststreptococcal acute glomerulonephritis. The severity of the histologic process correlates with the clinical severity of the initial phase of the disease, and it may correlate with the ultimate prognosis (ie, severe lesions have worse prognoses).

Light microscopy
As observed by light microscopy, glomerular changes are generalized and diffuse. The glomerular tufts usually appear enlarged and swollen, often filling the Bowman space, and a moderate to marked increase in proliferation of mesangial and epithelial cells is present. Polymorphonuclear leukocytes are also often observed as part of the inflammatory process, and monocytes may also be present. In persons with the most severe disease, the glomeruli appear bloodless because of the associated edema of the capillary walls, which impedes glomerular perfusion. The increased cell mass expands the central lobular area in a centrifugal pattern, leading to narrowing of the capillary lumens. When the inflammatory process is extensive, the epithelial cells of Bowman capsule proliferate, forming crescents. Few, if any, tubular changes are noted. Granular deposits of immunoglobulin (Ig) G and C3 along the capillary walls are typically found when the specimen is studied by immunofluorescent microscopy early in the course of the disease; other immunoglobulins (eg, IgM), complement components (eg, C4), properdin, and fibrinogen are often observed. Later in the course of the disease, the immunoreactants are observed primarily in the mesangium. In the nonstreptococcal forms of postinfectious glomerulonephritis, no significant deposition of complement components is present, although either IgG or IgM may be observed (as may IgA in persons with Henoch-Schnlein purpura or IgA nephropathy).

Electron microscopy
Electron microscopy of renal tissue from patients with APSGN usually reveals electron-dense deposits (humps) in the subepithelial space, mostly in hte mesangial notch near the glomerular basement membrane reflection over mesangium. A positive correlation exists between glomerular hypercellularity and subepithelial hump formation. During the recovery process, these deposits rapidly disappear, although fragments still may be found in the mesangium, with occasional subepithelial humps with electron-lucent areas. In persistent disease, these humps may not disappear so rapidly.

Consultations
The general pediatrician should be capable of treating patients with mild to moderate acute glomerulonephritis. Consultation with a pediatric nephrologist is necessary when 1 or more of the following are present: Severe hypertension Severe oliguria Severe edema Nephrotic-range proteinuria Azotemia (moderate to marked) Recurrent episodes of gross hematuria Persistently depressed C3 (past 8-10 wk) For failure of expected resolution of clinical signs, consultation is indicated for the following: Gross hematuria within the preceding 10-14 days Microscopic hematuria within 1 year Edema within 2 weeks Proteinuria (>50 mg/dL) within 6 months Azotemia within 1 week Hypertension within 6 weeks

Long-Term Monitoring
Long-term follow-up for a patient following acute poststreptococcal glomerulonephritis (APSGN) primarily consists of blood pressure measurements and urine examinations for protein and blood. In general, examinations are performed at 4- to 6-week intervals for the first 6 months and at 3- to 6-month intervals thereafter, until both hematuria and proteinuria have been absent and the blood pressure has been normal for 1 year. Documenting that the low C3 has returned to normal after 8-10 weeks may be useful. Follow up at 0-6 weeks as frequently as necessary to determine the following: Hypertension has been controlled. Edema has started to resolve. Gross hematuria has resolved. Azotemia has resolved. Follow up at 8-10 weeks after onset to assess the following: Azotemia has subsided. Anemia has been corrected. Hypertension has resolved. C3 and C4 concentrations have returned to normal. Follow up at 3, 6, and 9 months after onset to check the following: Hematuria and proteinuria are subsiding gradually. Blood pressure is normal. Follow up at 12 months after onset to evaluate that proteinuria and microscopic hematuria have disappeared. Follow up at 2, 5, and 10 years after onset to check the patient's urine, blood pressure, and serum creatinine level are normal.

Prevention of APSGN
A vaccine targeted against group A streptococci will prevent both invasive disease and nonsuppurative complications. The current thrust of group A streptococcal vaccine research has been to target the M protein.[68] A 26-valent vaccine as been developed that targets the variable region of the M proteins of the most common rheumatogenic cocci. Unfortunately, no M protein from nephritogenic streptococci were

included in the vaccine. In addition, the most common M protein types in the developing world differ from those of more developed countries, thus rendering the vaccine less efficacious. The most effective public health measure in the developing world is to improve hygiene and provide better housing conditions to avoid overcrowding. This offers the best hope for elimination of epidemic pyoderma and thus preventing APSGN.

Approach Considerations
By the time the child with acute poststreptococcal glomerulonephritis (APSGN) presents with symptoms, the glomerular injury has already occurred, and the healing process has begun. Thus, influencing the ultimate course of the disease by any specific therapy directed at the cause of the nephritis is not possible. Conversely, morbidity and early mortality are influenced considerably by appropriate medical therapy. Even then, treatment is usually supportive and directed toward the potential complications. Only a small percentage of patients with acute glomerulonephritis require initial hospitalization, and most of those are ready for discharge in 2-4 days. As soon as the blood pressure (BP) is under relatively good control and diuresis has begun, most children can be discharged and monitored as outpatients. If indicated at any time during the course of the disease, an experienced nephrologist should perform renal biopsy percutaneously. Transfer of responsibility for the patient with acute glomerulonephritis is rarely indicated, except in those instances in which a consultation with a nephrologist is not easily obtainable in the local area or by telephone, facsimile, or e-mail. See Consultations for instances that necessitate consultation with a pediatric nephrologist. See also Acute Glomerulonephritis and Emergent Management of Acute Glomerulonephritis.

Diet and activity

A low-sodium, low-protein diet should be prescribed during the acute phase, when edema and hypertension are in evidence; however, prolonged dietary restrictions are not warranted. Limitation of fluid and salt intake is recommended in the child who has either oliguria or edema. Curtailment of fluid to amounts consistent with insensible losses helps to minimize vascular overload and hypertension. Limited activity is probably indicated during the early phase of the disease, particularly if hypertension is present. Bedrest may lessen the degree and duration of gross hematuria if present; however, longer periods of bedrest do not appear to influence the course or long-term prognosis; therefore, they are generally not recommended.

Inpatient Management
General management begins with a decision to admit the child with acute glomerulonephritis to the hospital or merely have him or her undergo frequent outpatient examinations. Hospitalization is indicated if the child has significant hypertension or a combination of oliguria, generalized edema, and elevation of serum creatinine or potassium.

Severe hypertension
Severe hypertension, or that associated with signs of cerebral dysfunction, demands immediate attention. Debate exists regarding the agent that is most effective in patients with severe hypertension. Three drugs are commonly cited as having a high benefit-to-risk ratio: labetalol (0.5-2 mg/kg/h intravenously [IV]), diazoxide, and nitroprusside (0.5-2 mcg/kg/min IV; in patients with severe hypertension that is refractory to the previous agents). In combination with any of these agents, the simultaneous IV administration of furosemide at doses of 2 mg/kg may be merited. Diazoxide use for blood pressure (BP) control is limited because, once administered, no further control of pressure is possible, unlike labetalol or nitroprusside.

Severe hypertension without encephalopathy can be treated in the manner described above or, more commonly, by administration of vasodilator drugs, such as hydralazine or nifedipine. The doses of these drugs can be administered either by injection or by mouth and can be repeated every 10-20 minutes until a suitable response is obtained. For most children, the need for more than 2-3 doses is unusual.

Mild-to-moderate hypertension
Mild-to-moderate hypertension does not warrant emergency management and is treated most effectively with bedrest, fluid restriction, and less-frequent doses of the medications mentioned above. The use of loop diuretics, such as furosemide (1-3 mg/kg/d oral [PO], administered 1-2 times daily), may hasten resolution of the hypertension. For patients resistant to treatment, either hydralazine or nifedipine is indicated. Angiotensin-converting enzyme (ACE) inhibitors are effective, although these agents have the potential to produce hyperkalemia and usually are not first-line drugs in acute glomerulonephritis. Edema and circulatory congestion are usually not sufficiently marked to produce more than minimal discomfort. Restriction of fluids to those amounts needed to replace insensible losses is the best treatment for edema and circulatory congestion. Loop diuretics (furosemide) administered PO have been reported to reduce the length of hospitalization in children who are edematous. If congestion is marked, administer furosemide parenterally (2 mg/kg). Phlebotomy, rotating tourniquets, dialysis, or digitalization is rarely necessary.

Anuria or oliguria
Anuria or severe and persistent oliguria may occur in 3-6% of children with acute glomerulonephritis and may necessitate hospitalization. Fortunately, both of these conditions are usually transient. Because they may be ototoxic, avoid large doses of furosemide in children with symptoms of anuria or severe and persistent oliguria. In addition, osmotic diuretics, such as mannitol, are contraindicated, as they might increase vascular volume.

Other medical management strategies

A course of penicillin can be administered to avoid contamination of contacts with a nephritogenic strain of streptococci; however, in most instances, these contacts do not develop overt acute glomerulonephritis.[37] Such therapy may not influence the course of the disease in the index patient, but it may alter the response that confers type-specific immunity. To date, only one report suggests that patients with APSGN who receive antibiotic treatment have a milder clinical course. [62]Throat cultures of immediate family members might detect patients who are asymptomatic but infected. The diagnosis of streptococcal pharyngitis on clinical grounds alone is uncertain, and only 10-20% of the patients who present with sore throat in general clinical practice have a positive culture for group A streptococci.[63] Several clinical scoring systems have been developed to increase the accuracy of diagnosis for the prescription of antibiotics. The most commonly used is that of Centor et al [64] and McIsaac et al.[65] These have a range of 1-4 and incorporate age as a risk factor. The following is the McIsaac score, showing each criterion and its corresponding score: Temperature higher than 38 C and no cough - 1 point Tender anterior cervical adenopathy - 1 point Tonsillar swelling or exudates - 1 point Age between 3 and 14 years - 1 point

Age 15-44 years is assigned no points, and age older than or equal to 44 years garners -1 point. Based on the scoring systems, it is recommended that antibiotic treatment is administered based on clinical grounds alone when the score is 4, antibiotic treatment is not recommended (and culture is unnecessary) when the score is 0 or 1, and culture should be obtained and treatment given only when the result is positive if the score is 2 or 3. Rapid test for streptococcal antigen detection may be used as a confirmatory test for children with tonsillar exuduate.[66] However, the sensitivity is too low to support use without culture confirmation of negative results.[67] In resource-limited settings, the author is of the view that all patients with acute APSGN be treated as though they have active streptococcal infection. This recommendation is based on the finding of positive cultures for Streptococcus in patients with APSGN in whom upper respiratory tract or skin infections are not clinically evident. Steroid therapy is indicated only in patients with severe crescentic glomerulonephritis or in those with rapidly progressive glomerulonephritis. Selected patients with Henoch-Schnlein purpura (HSP) nephritis and membranoproliferative glomerulonephritis (MPGN) also may benefit from such agents. An experienced nephrologist should make decisions regarding the indication for such treatment.

Medication Summary
The need for medicines in acute poststreptococcal glomerulonephritis (ASPGN) is usually limited in scope and in length. Administer antibiotics (penicillin or erythromycin) for 10 days to ensure eradication of the streptococcus if the disease is believed to be acute poststreptococcal glomerulonephritis and if risk of contamination is present. Some clinicians use this treatment only when evidence suggests an active infection. Antihypertensives are usually not necessary after the child leaves the hospital, although mild hypertension may persist for as many as 6 weeks. The medications that can be used span the entire range of antihypertensives, such as vasodilators (eg, hydralazine), calcium channel-blocking agents (eg, long-acting nifedipine, amlodipine), or angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril). Carefully monitor blood pressure (BP) for at least 1 week after the drug is discontinued to ensure that rebound hypertension does not occur. Diuretic agents (eg, furosemide) are rarely necessary after the first 2 days; hypertension persisting beyond the first week may suggest a diagnosis other than acute glomerulonephritis.

Antihypertensives
Class Summary
Antihypertensive agents are commonly used during initial phase of acute glomerulonephritis.
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Amlodipine (Norvasc)
Amlodipine is generally regarded as a dihydropyridine, although experimental evidence suggests that it may also bind to the nondihydropyridine binding sites. Amlodipine blocks postexcitation release of calcium ions into cardiac and vascular smooth muscle, thereby inhibiting the activation of ATPase on myofibril contraction. The overall effect is reduced intracellular calcium levels in cardiac and smooth muscle cells of the coronary and peripheral vasculature, resulting in dilatation of the coronary and peripheral arteries. This drug may also potentiate angiotensinconverting enzyme (ACE) inhibitor effects. During depolarization, amlodipine inhibits calcium ions from entering the slow channels and voltagesensitive areas of vascular smooth muscle and myocardium, which benefits nonpregnant patients with systolic dysfunction, hypertension, or arrhythmias. This agent a substantially longer half-life than nifedipine and diltiazem and is administered once daily.
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Diazoxide (Proglycem)
Diazoxide is a diuretic benzothiazine antihypertensive agent that may be indicated for emergency reduction of severe hypertension. This drug should only be administered intravenously (IV). Diazoxide produces direct smooth muscle relaxation of peripheral arterioles, which decreases BP.
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Furosemide (Lasix)
Furosemide is a loop diuretic that is useful in patients with acute glomerulonephritis who are edematous. This agent also has some BP-lowering effect by increasing excretion of salt and water via interfering with

the chloride-binding cotransport system in the ascending loop of Henle. In acute hypertensive states, administer furosemide intravenously (IV).
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Labetalol (Trandate)
Labetalol blocks beta1-adrenergic, alpha-adrenergic, and beta2-adrenergic receptor sites, thereby decreasing BP.
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Hydralazine
Hydralazine decreases systemic resistance through direct vasodilation of arterioles.
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Nifedipine (Adalat, Procardia, Nifediac)

Nifedipine relaxes coronary smooth muscle and produces coronary vasodilation, which, in turn, improves myocardial oxygen delivery.
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Nitroprusside (Nitropress)
Nitroprusside produces vasodilation and increases the inotropic activity of the heart. However, higher dosages may exacerbate myocardial ischemia by increasing the heart rate.

Antibiotics
Class Summary
Administer antibiotics for 10 days to ensure eradication of streptococci, if the disease is believed to be poststreptococcal acute glomerulonephritis and risk of contamination is present.
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Penicillin VK
Penicillin VK inhibits biosynthesis of cell wall mucopeptide and is bactericidal against sensitive organisms when adequate concentrations are reached. This agent is most effective during the stage of active multiplication.
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Erythromycin base (E.E.S., EryPed, Ery-Tab, Erythrocin)

Erythromycin inhibits bacterial growth, possibly by blocking the dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest