Infection-related glomerulonephritis (IRGN) results from a recently resolved infection or an infection that is ongoing at the time of development of glomerulonephritis. IRGN is preferred to the formerly used term “postinfectious glomerulonephritis,” which adequately described classic poststreptococcal glomerulonephritis but did not address the increasingly recognized forms of glomerulonephritis that are manifestations of ongoing infection and nonstreptococcal infectious agents. Diabetes is the most common comorbidity (malignancy, immunosuppression, AIDS, alcoholism, and injection drug use are other recognized comorbidities), and older age is a key risk factor. Patients over 65 years of age account for about one third of IRGN cases in the developed world.
The incidence of poststreptococcal glomerulonephritis has declined throughout most of the world due to improvements in infection control and sanitation. The entity, however, remains a health concern in developing countries: More than 450,000 cases of poststreptococcal glomerulonephritis occur worldwide annually, resulting in approximately 5000 deaths, with >95% of these cases in less developed countries. In industrialized countries, much of the burden of IRGN has shifted from children to adults, with a decrease in IRGN attributed to streptococcal infections and an increase in IRGN cases associated with Staphylococcus aureus and gram-negative bacteria.
In the classical view of the pathogenesis of IRGN, antibodies directed at bacterial antigens form immune complexes in the circulation that subsequently deposit in the glomerulus. Additionally, however, antibodies directed at bacterial antigens planted within glomeruli can result in in situ formation of glomerular immune complexes.
The variable presentation of IRGN ranges from asymptomatic microscopic hematuria to RPGN. Proteinuria is usually subnephrotic.
In classic poststreptococcal glomerulonephritis, symptomatic patients (typically children) present with an acute nephritic syndrome of hematuria, proteinuria, hypertension, edema, and, in some cases, kidney dysfunction. The urine sediment is active with dysmorphic erythrocytes, erythrocyte casts, and leukocyturia. Hypocomplementemia is very common, with decreased C3 in up to 90% of cases. There is usually a latent period (1 to 2 weeks after upper respiratory infections; 2 to 4 weeks after skin infections) between the resolution of the streptococcal infection and the onset of the nephritic syndrome. Serologic markers of a recent streptococcal infection, including elevated antistreptolysin O, antistreptokinase, antihyaluronidase, and antideoxyribonuclease B antibody levels, are often detected. In adults, most cases of IRGN are no longer poststreptococcal, and the glomerulonephritis often coexists with the triggering infection. Low complement levels may be absent in these peri-infectious cases.
The diagnosis of IRGN can be made clinically in the appropriate setting (for example, classic nephritic presentation with low complements and clear evidence of a recent infection), although the only definitive way to make the diagnosis is by kidney biopsy. The most common finding on light microscopy is a proliferative glomerulonephritis with significant presence of infiltrating neutrophils. On electron microscopy, the classic finding in poststreptococcal glomerulonephritis is hump-shaped subepithelial electron dense deposits, although these are not required for the diagnosis of IRGN.
Treatment is typically supportive and aimed at the infectious etiology, although in some cases with severe proliferative glomerulonephritis on biopsy, a trial of glucocorticoids is used.
In children, prognosis for complete recovery is excellent, and treatment usually is supportive and aimed at the infecting organism. The prognosis of the newly recognized forms of IRGN (for example, due to S. aureus and gram-negative organisms) in adults is different, with more patients developing severe kidney dysfunction and progressing to CKD and sometimes ESKD.