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. In patients with oliguric acute kidney injury, potassium intake should be restricted to prevent hyperkalemia.
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.
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:
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Severe hypertension
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Severe oliguria
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Severe edema
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Nephrotic-range proteinuria
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Azotemia (moderate to marked)
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Recurrent episodes of gross hematuria
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Persistently depressed C3 (past 8-10 wk)
For failure of expected resolution of clinical signs, consultation is indicated for the following:
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Gross hematuria within the preceding 10-14 days
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Microscopic hematuria within 1 year
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Edema within 2 weeks
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Proteinuria (>50 mg/dL) within 6 months
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Azotemia within 1 week
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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:
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Hypertension has been controlled.
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Edema has started to resolve.
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Gross hematuria has resolved.
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Azotemia has resolved.
Follow up at 8-10 weeks after onset to assess the following:
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Azotemia has subsided.
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Anemia has been corrected.
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Hypertension has resolved.
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C3 and C4 concentrations have returned to normal.
Follow up at 3, 6, and 9 months after onset to check the following:
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Hematuria and proteinuria are subsiding gradually.
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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. [64] A 26-valent vaccine has 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.
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). Recently, sodium nitroprusside has been replaced by the use of nicardipine in the United States and much of Western Europe (start at 5 mg/h intravenously [IV], increase by 2.5 mg/h every 5-15 min as needed, maximum dose 15 mg/h). Discontinue if hypotension or tachycardia is present (may restart at 3-5 mg/h IV). 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. [38] 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. [65] 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. [66] 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 [67] and McIsaac et al. [68] 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:
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Temperature higher than 38º C and no cough - 1 point
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Tender anterior cervical adenopathy - 1 point
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Tonsillar swelling or exudates - 1 point
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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 exudate. [69] However, the sensitivity is too low to support use without culture confirmation of negative results. [70]
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-Schönlein 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.
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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.
