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 infection. [44] 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).
A study by Ayoob and Schwaderer indicated that a small subset of children with acute poststreptococcal glomerulonephritis may demonstrate features similar to those found in systemic lupus erythematosus nephritis, including acute kidney injury, antinuclear antibody positivity, and hematologic anomalies. [45]
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. [46] 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. [47, 48, 49, 50, 51] 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. [50] Males are 2 times more likely to have this condition compared with females; the reason this difference in sex prevalence is not known. [47, 50, 51] 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 2-4% of cases. [47] . 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. [52, 53]
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. [52]
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, 54] Numerous case reports describe children who present with extreme manifestations, usually hypertensive encephalopathy, who do not display the typical urinary findings at presentation. [55] 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.
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Schematic representation of proposed mechanisms involved in the development of acute poststreptococcal glomerulonephritis (APSGN).MES: mesangial cell; END: endothelial cell; PMN: polymorphonuclear cell; MΦ: macrophage; T: T lymphocyte; GMB: glomerular basement membrane; C: complement; Anti-NAPlr-Ab: Anti-NAPlr-antibody. 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.
