Postinfectious Glomerulonephritis (PIGN)

Postinfectious glomerulonephritis (PIGN), a nephritic syndrome Overview of Nephritic Syndrome Nephritic syndrome is defined by hematuria, variable degrees of proteinuria, usually dysmorphic red blood cells (RBCs), and often RBC casts on microscopic examination of urinary sediment. Often... read more , is the most common cause of a glomerular disorder in children between 5 and 15 years; it is rare in children < 2 years and uncommon in adults > 40 years.

Most cases are caused by nephritogenic strains of group A beta-hemolytic streptococci, most notably type 12 (which causes pharyngitis Tonsillopharyngitis Tonsillopharyngitis is acute infection of the pharynx, palatine tonsils, or both. Symptoms may include sore throat, odynophagia, cervical lymphadenopathy, and fever. Diagnosis is clinical, supplemented... read more ) and type 49 (which causes impetigo Impetigo and Ecthyma Impetigo is a superficial skin infection with crusting or bullae caused by streptococci, staphylococci, or both. Ecthyma is an ulcerative form of impetigo. Diagnosis is clinical. Treatment is... read more ); an estimated 5 to 10% of patients with streptococcal pharyngitis and about 25% of those with impetigo develop PIGN. A latency period of 6 to 21 days between infection and glomerulonephritis onset is typical, but latency may extend up to 6 weeks.

Less common pathogens are nonstreptococcal bacteria, viruses, parasites, rickettsiae, and fungi (see table Causes of Glomerulonephritis Causes of Glomerulonephritis ). Bacterial endocarditis Infective Endocarditis Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more and ventriculoatrial shunt Treatment Hydrocephalus is accumulation of excessive amounts of CSF, causing cerebral ventricular enlargement and/or increased intracranial pressure. Manifestations can include enlarged head, bulging... read more infections are additional important conditions in which PIGN develops; ventriculoperitoneal shunts are more resistant to infection.

The mechanism is unknown, but microbial antigens are thought to bind to the glomerular basement membrane and activate primarily the alternate complement pathway both directly and via interaction with circulating antibodies, causing glomerular damage, which may be focal or diffuse. Alternatively, circulating immune complexes could precipitate on the glomerular basement membrane.

Symptoms and signs range from asymptomatic hematuria (in about 50%) and mild proteinuria to full-blown nephritis with microscopic or gross hematuria (cola-colored, brown, smoky, or frankly bloody urine), proteinuria (sometimes nephrotic-range), oliguria, edema, hypertension, and renal insufficiency. Fever is unusual and suggests persistent infection.

Renal failure that causes fluid overload with heart failure and severe hypertension requiring dialysis affects 1 to 2% of patients.

Uncommonly, nephrotic syndrome may persist after resolution of severe disease.

Clinical manifestations of nonstreptococcal PIGN may mimic other disorders (eg, polyarteritis nodosa, renal emboli, antimicrobial drug–induced acute interstitial nephritis).

Streptococcal postinfectious glomerulonephritis (PIGN) is suggested by history of pharyngitis Tonsillopharyngitis Tonsillopharyngitis is acute infection of the pharynx, palatine tonsils, or both. Symptoms may include sore throat, odynophagia, cervical lymphadenopathy, and fever. Diagnosis is clinical, supplemented... read more or impetigo Impetigo and Ecthyma Impetigo is a superficial skin infection with crusting or bullae caused by streptococci, staphylococci, or both. Ecthyma is an ulcerative form of impetigo. Diagnosis is clinical. Treatment is... read more plus either typical symptoms of PIGN or incidental findings on urinalysis. Demonstration of hypocomplementemia is essentially confirmatory.

Tests done to confirm the diagnosis depend on clinical findings. Antistreptolysin O, antihyaluronidase, and antideoxyribonuclease (anti-DNAase) antibodies are commonly measured. Serum creatinine and complement levels (C3 and total hemolytic complement activity) are also usually measured; however, in patients with typical clinical findings, some tests can be omitted. Sometimes other tests are done. Biopsy confirms the diagnosis but is rarely necessary.

Antistreptolysin O level, the most common laboratory evidence of recent streptococcal infection, increases and remains elevated for several months in about 75% of patients with pharyngitis and in about 50% of patients with impetigo, but it is not specific. The streptozyme test, which additionally measures antihyaluronidase, antideoxyribonuclease, and other titers detects 95% of recent streptococcal pharyngitis and 80% of skin infections.

Urinalysis typically shows proteinuria (0.5 to 2 g/m²/day); dysmorphic RBCs; WBCs; renal tubular cells; and possibly RBC, WBC, and granular casts. Random (spot) urinary protein/creatinine ratio is usually between 0.2 and 2 (normal, < 0.2) but may occasionally be in the nephrotic range (≥ 3).

Serum creatinine may rise rapidly but usually peaks below a level requiring dialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more .

C3 and total hemolytic complement activity (CH50) levels fall during active disease and return to normal within 6 to 8 weeks in 80% of PIGN cases; C1q, C2, and C4 levels are only minimally decreased or remain normal. Cryoglobulinemia may appear and persist for several months, whereas circulating immune complexes are detectable for only a few weeks.

Biopsy specimens show enlarged and hypercellular glomeruli, initially with neutrophilic infiltration and later with mononuclear infiltration. Epithelial cell hyperplasia is a common early, transient feature. Microthrombosis may occur; if damage is severe, hemodynamic changes due to cellular proliferation and edema of the glomerulus cause oliguria, occasionally accompanied by epithelial crescents (formed within Bowman space from epithelial cell hyperplasia). Endothelial and mesangial cells multiply, and the mesangial regions often are greatly expanded by edema and contain neutrophils, dead cells, cellular debris, and subepithelial deposits of electron-dense material.

Immunofluorescence microscopy usually shows immune complex deposition with IgG and complement in a granular pattern. On electron microscopy, these deposits are semilunar or hump-shaped and are located in the subepithelial area. The presence of these deposits and of small subendothelial and mesangial deposits initiates a complement-mediated inflammatory reaction that leads to glomerular damage. The major antigen is probably Zymogen cysteine proteinase exotoxin B (Zymogen/SPE B).

Normal renal function is retained or regained by 85 to 95% of patients. Glomerular filtration rate (GFR) usually returns to normal over 1 to 3 months, but proteinuria may persist for 6 to 12 months and microscopic hematuria for several years. Transient changes in urinary sediment may recur with minor upper respiratory infections. Renal cellular proliferation disappears within weeks, but residual sclerosis is common. In 10% of adults and 1% of children, postinfectious glomerulonephritis evolves into rapidly progressive glomerulonephritis Rapidly Progressive Glomerulonephritis (RPGN) Rapidly progressive glomerulonephritis is acute nephritic syndrome accompanied by microscopic glomerular crescent formation with progression to renal failure within weeks to months. Diagnosis... read more .

Treatment is supportive and may include restriction of dietary protein, sodium, and fluid and, in more severe cases, treatment of edema Treatment Edema is swelling of soft tissues due to increased interstitial fluid. The fluid is predominantly water, but protein and cell-rich fluid can accumulate if there is infection or lymphatic obstruction... read more and hypertension Treatment Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more . Dialysis Hemodialysis In hemodialysis, a patient’s blood is pumped into a dialyzer containing 2 fluid compartments configured as bundles of hollow fiber capillary tubes or as parallel, sandwiched sheets of semipermeable... read more is occasionally necessary. Antimicrobial therapy is preventive only when given within 36 hours of infection and before glomerulonephritis becomes established.