Glomerulonephritis Associated with Nonstreptococcal Infection

Most glomerular diseases associated with infection are mediated by immune complexes. The classic example observed in poststreptococcal GN involves an antigen-antibody reaction, which may occur in the circulation or in the glomerulus. Deposition in the glomerulus results in activation of the complement cascade, which may involve either the classic or alternative pathway. The immune complexes may activate endogenous glomerular cells. The reduction of chemotactic factors results in the accumulation of leukocytes and platelets within the glomerulus and, consequently, the inflammatory response.

The pathogenesis of glomerulonephritis related to staphylococcal infection is not fully understood. Bacterial superantigens may play a key role in the pathological change. A staphylococcal antigen (eg, enterotoxins C and A and toxic shock syndrome toxin [TSST]-1) act as a superantigen and it can bind directly to the major histocompatibility complex (MHC) class II molecules on antigen-presenting cells. This complex then binds to the T-cell receptor without MHC restriction. The interaction results in massive T-cell activation and a subsequent cytokine burst. The cytokines cause polyclonal B-cell activation that induces the production of IgA, IgG, and IgM. These components have a natural specificity for staphylococcal antigens such as those on the cell envelope. ^[4]

Several possible pathogenic events occur in viral diseases associated with glomerular injury, including the following:

• Formation of circulating immune complexes involving viral antigens and antibodies
• Formation of circulating immune complexes induced by the release of antigens following virally induced cellular injury
• Formation of in situ antigen-antibody reactions or cell-mediated injury
• Autoimmune reactions to glomerular structures induced by the virus

In protozoal infections, such as malaria, antibodies are formed against malarial antigens. The circulating immune complexes activate complement and macrophages. The complexes are primarily deposited in subendothelial areas. A cell-mediated immune response may also occur.

Postinfectious glomerulonephritis (PIGN) may occur in association with bacterial, viral, protozoal, and helminthic or fungal infections. See Table 1. below.

Table 1. Infectious agents associated with PIGN (Open Table in a new window)

Bacterial endocarditis: PIGN occurs more commonly in subacute rather than acute endocarditis. Currently, S aureus is the most common pathogen recognized. ^[13]  Shunt nephritis may be associated with ventriculovascular, ventriculoperitoneal, peritoneovascular, or vascular shunts. ^[14]

The various causes of infection-related GN have different prevalence rates. In endocarditis, associated GN may occur in up to 20% of cases. ^[15] Staphylococcus aureus has become a more common cause of GN than Streptococcus in developed countries. ^[4] GN associated with hepatitis C is becoming a far more commonly recognized cause of GN. ^{[16, 17]} It is estimated that 35–60% of patients with chronic hepatitis C will develop renal manifestations including type I membranoproliferative glomerulonephritis (MPGN), mesangial glomerulonephritis, and focal and segmental glomerulonephritis. ^[18]  

Although specific incidence statistics are not available, in certain developing areas of the world, hepatitis B, HIV disease, malaria, and schistosomiasis are major causes of glomerulopathy. The incidence of GN in malaria is estimated to be around 18%. ^[11] GN is present in approximately 15% of patients with schistosomiasis. ^[12]

In most GNs associated with infection, no racial or sexual predilection exists. However, HIV-associated GN is far more common in males. Although classic postinfectious GN primarily occurs in childhood, it has been documented in all age groups. Glomerulonephritis associated with methicillin-resistant Staphylococcus aureus (MRSA) infection is 3 times more common in older patients in developed countries. ^[4]

Depending on the etiology, the outcome of GN associated with infection can be quite variable. Complete recovery occurs in most patients, even those patients with crescents observed in kidney biopsy tissue. The outcome depends on the duration of infection before specific antibacterial or other antiinfective therapy is initiated.  

The prognosis for shunt nephritis is good with early diagnosis and treatment of the infection. Approximately 30% of ventriculovascular shunts  become infected and GN develops in 0.7–2% of the infected shunts. Ventriculoperitoneal shunts are rarely complicated with GN. Staphylococcus epidermidis or S aureus are the most common pathogens. A late diagnosis delays antibiotic therapy and removal of the shunt, resulting in a worse renal prognosis. ^[3]

In schistosomal infections, progression of renal disease is common, even after treatment.

Age >65 years and comorbid diabetes are independent risk factors of poor prognosis for GN related to staphylococcal infection. ^[4]

In GN associated with bacterial endocarditis, renal function returns after treatment with antibiotics. The GN usually resolves after the infection has cleared, with renal function beginning to improve within 1-2 weeks, complement levels normalizing within 6 weeks, and hematuria normalizing in approximately 6 months. ^[15]

The course of GNs associated with viral infection is more variable, although patients with HIV nephropathy commonly progress to end-stage renal disease. ^[19]