Postinfectious Glomerulonephritis

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Jan A. Bruijn

Introduction/Clinical Setting

Acute postinfectious glomerulonephritis is a kidney disease that follows after an infection. The most common and best understood form of acute postinfectious glomerulonephritis is poststreptococcal glomerulonephritis. Less is known about the other forms of postinfectious glomerulonephritis. In addition, there are glomerulonephritides that occur during persistent bacterial infections such as bacterial endocarditis, deep abscesses, and infected atrioventricular shunts in hydrocephalus (1).

A large number of bacterial, viral, and mycotic infections may be followed by acute glomerulonephritis. Especially after bacterial and viral infections, a proliferative form of glomerulonephritis occurs (2). In parasitic infections membranous or membranoproliferative forms are seen more often, with in general a worse prognosis. However, most cases of acute postinfectious glomerulonephritis are caused by group A streptococci and follow upper airway infections, such as pharyngitis or tonsillitis, by 14 to 21 days (3). Especially in warmer climates acute glomerulonephri-tis may also follow after skin infections. In recent decades the number of patients with poststreptococcal glomerulonephritis has decreased considerably in the United States and Europe. In the Western world, staphylococ-cus or gram-negative bacteria are now more often the cause of acute postinfectious glomerulonephritis than is streptococcus (4). In other parts of the world the incidence of poststreptococcal glomerulonephritis has remained high. In addition to the declining incidence, the number of biopsies with acute glomerulonephritis decreases because the clinician is less inclined to take a biopsy in a patient with classical or typical symptoms of acute postinfectious glomerulonephritis. The disease occurs especially in children between the ages of 2 and 12 years and young adults, and more often in men than in women (5-7). Clinically the disease is characterized by an acute nephritic syndrome (acute glomerulonephritis). The symptoms include an abrupt onset of macroscopic hematuria, oliguria, acute renal failure manifested by a sudden decrease in the glomerular filtration rate, and fluid retention manifested by edema and hypertension (3). Edema probably results from renal sodium retention caused by the sudden decrease in the glomerular filtration rate, rather than occurring as a consequence of hypoalbuminemia as in the nephrotic syndrome (6). Laboratory studies are directed at the urine sediment, proteinuria, renal function, and proving the immune response to streptococcal (antistreptolysin O, streptozyme) or viral antigens (3,8). Complement abnormalities include a large reduction in total serum hemolytic complement CH50 and C3 concentrations in many cases with normal C4, suggesting complement activation primarily via the alternative pathway (3).

Pathologic Findings Light Microscopy

In acute glomerulonephritis usually all glomeruli are affected ("diffuse") and all to a similar extent ("global"). The glomerular capillaries are dilated and hypercellular, without necrosis. In addition to an increase of endothe-lial and mesangial cells, influx of inflammatory cells is present, especially neutrophilic granulocytes and monocytes (Fig. 5.1). Because of the large numbers of granulocytes the term exudative glomerulonephritis is used. Eosinophils and lymphocytes may occur, but they are usually scarce. The glomerular capillary walls are sometimes slightly thickened locally. In some biopsies using high magnification, small nodules may be seen on the epithelial side of the glomerular capillary walls, especially in the trichrome or toluidine-blue stains. These correspond to the subepithelial deposits ("humps") that are seen electron microscopically (see below). In severe cases extracapillary proliferation with formation of crescents and/or adhesions (synechiae) can be seen. In Bowman's space erythrocytes and some-

Figure 5.1. Diffusely hypercellular glomerulus in acute postinfectious glomerulonephritis with massive influx of neutrophilic polymorphonuclear granulocytes (Jones silver stain).

Jones Silver Stain Normal Glomeruli

Figure 5.1. Diffusely hypercellular glomerulus in acute postinfectious glomerulonephritis with massive influx of neutrophilic polymorphonuclear granulocytes (Jones silver stain).

times granulocytes may be present. In renal biopsies taken a few weeks after the first clinical symptoms occurred, the picture is often more quiet. The number of granulocytes has decreased, the glomerular capillary walls have shrunk, the number of humps decreases, and the capillary walls are slender. In this stage diffuse mesangial hypercellularity may still be seen, and this can remain for several months. Evidence of resolving or largely healed postinfectious glomerulonephritis may be overlooked (9). This substantiates the contention that postinfectious glomerulonephritis occurs more frequently than is clinically appreciated (10).

Tubular changes are less prominent than glomerular alterations. When proteinuria occurs, reabsorption droplets can be seen in the proximal tubular epithelial cells. In the lumen of tubules protein cylinders, erythro-cytes and sometimes granulocytes may be present. Tubular atrophy seldom occurs. The extent of interstitial damage varies, but is usually not extensive. Interstitial edema may be present with some mixed inflammatory infiltrate. Arteries and arterioles are usually unaffected.

Due to the combination of expansion of glomerular lobules, hypercellu-larity of the glomerular capillaries, and focal thickening of the capillary walls, postinfectious glomerulonephritis may be hard to distinguish from membranoproliferative glomerulonephritis light microscopically. Using immunofluorescence and electron microscopy a distinction between the two diseases can usually be made. However, a continuous, garland-type immunofluorescence pattern, although often considered typical for mem-branoproliferative glomerulonephritis, can also occur in postinfectious glomerulonephritis and is then related to a worse prognosis.

Immunofluorescence Microscopy

Immunofluorescence studies in biopsies taken during the first 2 to 3 weeks of the diseases most often show diffuse, irregular, coarse granular deposits of immunoglobulin G (IgG) and C3 along the glomerular capillary walls (Fig. 5.2). In large, confluent deposits the pattern may in places become continuous. In more than half of the cases IgM is also present, while IgA, IgE, and C1q are most often absent. Based on the distribution pattern of the immune complexes the morphology of postinfectious glomerulonephri-tis has been divided into several histologic subtypes, but these are not clearly related to clinical behavior or prognosis (11). Nasr and coworkers (12) described several cases of IgA-dominant acute poststaphylococcal glomerulonephritis complicating diabetic nephropathy.

Electron Microscopy

In acute glomerulonephritis, swelling of glomerular endothelial and mesan-gial cells is often seen electron microscopically. The glomerular basement membranes are usually of normal contour and thickness, although locally some thickening may occur. The glomerular basement membrane may also

Figure 5.2. Immunofluorescence showing distribution of IgG in a "punctate" pattern in acute postinfectious glomerulonephritis.

contain electron-lucent areas, possibly representing "resolving" deposits. The glomerular endothelium is often damaged and denuded. The most consistent classic change, however, is the presence of glomerular subepi-thelial cone-shaped electron dense deposits, referred to as "humps." These are especially numerous during the first weeks of acute glomerulonephritis and their number decreases thereafter (Fig. 5.3). The humps are sometimes separated from the lamina densa by a lucent zone, which is in continuity with the lamina rara externa. Epithelial cell pedicles overlying the

Meningioma Cell Line Picture
Figure 5.3. Electron microscopy showing large subepithelial electron dense deposits ("humps") and obliteration of visceral epithelial pedicles in acute postinfectious glomerulonephritis. Note absence of glomerular basement membrane (GBM) thickenings and spikes.

humps are often obliterated, with condensation of cytoplasmic microfilaments. In addition, some small irregular electron-dense deposits may be seen in the lamina densa, the mesangium, subendothelially, and sometimes along Bowman's capsule.


Poststreptococcal nephritis is an immunologically mediated disease, in which both humoral and cellular immune mechanisms seem to play a role. In general, immune complexes deposited in the glomeruli could consist of either streptococcal antigen-antibody complexes or autologous antigen-antibody complexes. Over the years a large number of streptococcal anti-genic fractions have been proposed as the putative target antigen, but only a few of these are still under active study (1). These include a protein fraction antigenically similar to streptokinase, and a cationic proteinase (13). Increasing evidence now points to an in situ antigen-antibody reactivity in poststreptococcal glomerulonephritis, as in a number of other glomerulo-nephritides (6,14,15). The cationic proteinase, due to its charge, is well able to pass the glomerular basement membrane and therefore should be able to induce subepithelial immune complex formation. The immune complexes induce further damage with the participation of the complement system and inflammatory cells as described in more detail in the chapters on membranous and lupus nephritides. The acute, nephritic, and endocap-illary proliferative nature of poststreptococcal glomerulonephritis is probably related to the early phase of the disease, usually preceding the time of biopsy, during which immune complexes are present subendothelially. Subsequently, the immune complexes dissociate and transmigrate through the glomerular basement membrane to reassociate and form complexes subepithelially. The search for a genetic marker of the disease has been unsuccessful, although familial incidence of poststreptococcal glomerulo-nephritis is almost 40% (13).

Clinicopathologic Correlations

The prognosis of postinfectious glomerulonephritis with respect to renal function is in general good, with over 95% of patients recovering spontaneously with return to normal renal function within 3 to 4 weeks and with no long-term sequelae, even when renal failure is severe enough to need dialysis (3). The prognosis becomes worse when crescents are present, and in patients with severe proliferative glomerulonephritis the symptoms may progress to oliguria or anuria (5). The presence of proteinuria is prognosti-cally a bad sign as well (16). The reported incidence of chronic renal insufficiency ranges from 0% to 20% (6). Novel molecular biologic techniques may allow more accurate determination of prognosis (17).


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2. Sotsiou F. Postinfectious glomerulonephritis. Nephrol Dial Transplant 16(suppl 6):68-70, 2001.

3. Couser WG. Glomerulonephritis. Lancet 353:1509-1515, 1999.

4. Montseny JJ, Meyrier A, Kleinknecht D, Callard P. The current spectrum of infectious glomerulonephritis. Experience with 76 patients and review of the literature. Medicine (Baltimore) 74:63-73, 1995.

5. Kline Bolton W, Sturgill BC. Proliferative glomerulonephritis: postinfectious, noninfectious, and crescentic forms. In: Tisher CC, Brenner BM, eds. Renal Pathology. Philadelphia: Lippincott, 1989:156-195.

6. Hricik DE, Chung-Park M, Sedor JR. Glomerulonephritis. N Engl J Med 339:888-900, 1998.

7. Matsukura H, Ohtsuki A, Fuchizawa T, Miyawaki T. Acute poststreptococcal glomerulonephritis mimicking Henoch-Schönleinpurpura. ClinNephrol 59: 6465, 2003.

8. Mori Y, Yamashita H, Umeda Y, et al. Association of parvovirus B19 infection with acute glomerulonephritis in healthy adults: case report and review of the literature. Clin Nephrol 57:69-73, 2002.

9. Haas M. Incidental healed postinfectious glomerulonephritis: a study of 1012 renal biopsy specimens examined by electron microscopy. Hum Pathol 34:310, 2003.

10. Ruiz P, Soares M. Acute postinfectious glomerulonephritis: an immune response gone bad? Hum Pathol 34:1-2, 2003.

11. Edelstein CL, Bates WD. Subtypes of acute postinfectious glomerulonephritis: a clinico-pathological correlation. Clin Nephrol 38:311-317, 1992.

12. Nasr AH, Markowitz GS, Whelan JD, et al. IgA-dominant acute poststaphy-lococcal glomerulonephritis complicating diabetic nephropathy. Hum Pathol 34:1235-1241, 2003.

13. Rodriguez-Iturbe B. Glomerulonephritis associated with infection. In: Massry SG, Glassock RJ, eds. Textbook of Nephrology, 3rd ed. Baltimore: Williams & Wilkins, 1995:698-710.

14. Bruijn JA, Hoedemaeker PJ. Nephritogenic immune reactions involving native renal antigens. In: Massry SG, Glassock RJ, eds. Textbook of Nephrology, 3rd ed. Baltimore: Williams & Wilkins, 1995:627-631.

15. Bruijn JA, de Heer E, Hoedemaeker PJ. Immune mechanisms in injury to glomeruli and tubulo-interstitial tissue. In: Jones TC, ed. Monographs on Pathology of Laboratory Animals. Urinary System, 2nd ed. New York: Springer-Verlag, 1998:199-224.

16. Rodriguez-Iturbe B. Postinfectious glomerulonephritis. Am J Kidney Dis 35: xlvi-xlviii, 2000.

17. Eikmans M, Baelde JJ, de Heer E, Bruijn JA. RNA expression profiling as prognostic tool in renal patients: toward nephrogenomics. Kidney Int 62:11251135, 2002.

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