Practice Essentials
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).
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.
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.
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.
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.
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.
In addition, nontypeable group A streptococci are frequently isolated from the skin or throat of patients with glomerulonephritis, representing presumably unclassified nephritogenic strains.
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 protein and the site of infection. The risk of developing nephritis infection by M type protein 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.
Diagnosis and treatment
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. A urinalysis is helpful, as microscopic hematuria is typically present in children with acute poststreptococcal glomerulonephritis. The disease is most common in children 4-12 years of age and rare before 2 years of age or in those individuals older than 18 years. The latency period from infection may vary from 1 to 2 weeks after pharyngitis to 3 to 6 weeks after skin infections.
The classic triad of gross hematuria, edema, and hypertension are the most common presenting symptoms. However, some patients may have a subclinical presentation with microscopic hematuria, minimal or no edema, and normal or just mildly elevated blood pressure. Hematuria is almost a universal finding with about one third of patients having gross hematuria. The dark urine is due to the oxidation of hemoglobin that turns brown after a prolonged time in an acidic environment. Gross hematuria may last up to 10 days and recur after a febrile illness. Edema occurs in about 65 -90% of patients and ascites is typically absent. Edema tends to last between 7-10 days. Pulmonary edema is uncommon except in the very severe cases. Hypertension occurs in about 60-80% of cases, present in the acute phase of the disease and is usually transient, lasting about 10 days. Hypertensive encephalopathy has been reported in about 11% of patients untreated in developing countries. Scanty urine or oliguria is seen in less than 50% of patients. Nonspecific symptoms included malaise, weakness, nausea and dull flank pain.
Recent poststreptococcal infection is most commonly demonstrated by serologic markers for elevated antibodies to extracellular streptococcal antigens.
By the time the child with acute poststreptococcal glomerulonephritis 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. This includes management of edema, hypertension, hyperkalemia, and impaired kidney function.
Initial management of edema and hypertension include some degree of fluid and salt restriction along with enhanced diuresis. Thiazides are the diuretics of choice as they lead not only to diuresis but also effective control of hypertension. However, they are not effective if the glomerular filtration rate drops to less than 30mls/min/1.73 sq. meters. When more significant edema is present or pulmonary edema, loop diuretics need to be used in high intravenous doses.
For more effective control of hypertension, use of B Blockers or calcium ion antagonist may be considered. The former can lead to hyperkalemia and the latter to fluid retention and should be closely monitored. Angiotensin converting enzyme antagonists and receptor blockers may be used but need to be closely monitored, especially in patients with declining kidney function as these agents may worsen glomerular filtration and lead to hyperkalemia.
Hyperkalemia is managed according to standard protocols. In patients with deteriorating kidney function (urea >35.7 mmol/l, intractable hyperkalemia and severe fluid overload with oligo-anuria, dialysis is indicated. The type of dialysis is dependent on the local expertise and by access to the various forms of therapy.
See also Acute Glomerulonephritis, Emergent Management of Acute Glomerulonephritis, and Rheumatic Heart Disease.