AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Background

The classic association of glomerulonephritis (GN) with infection is poststreptococcal GN, usually developing after streptococcal pharyngitis (see Glomerulonephritis, Poststreptococcal). However, a number of glomerular diseases are associated with other bacterial, viral, fungal, and parasitic diseases.

Pathophysiology

Most glomerular diseases associated with infection are mediated by the immune complex. 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.

Several possible pathogenic events occur in viral diseases associated with glomerular injury. These may include the 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, and 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.

Frequency

United States

The various causes of infection-related GN have different prevalence rates. In endocarditis, associated GN may occur in up to 20% of cases. Staphylococcus aureus has become a more common cause of GN than Streptococcus in developed countries. GN associated with hepatitis C is becoming a far more commonly recognized cause of GN.

International

Although specific numbers for incidence statistics are not available, in certain developing areas of the world, hepatitis B, HIV disease, malaria, and schistosomiasis are major causes of glomerulopathy.

Mortality/Morbidity

Depending on the etiology, the outcome of GN associated with infection can be quite variable.

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

Race

This condition is not limited to any particular race.

Sex

In most GNs associated with infection, no sexual predilection exists. However, HIV-associated GN is far more common in males.

Age

This type of GN can occur at any age.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

History

Presentation may vary from asymptomatic hematuria to a full-blown acute nephritic syndrome consisting of proteinuria, edema, hypertension, and renal failure.

• Hematuria may be gross or microscopic.
• Patients may have evidence of edema.
• Patients may report fever, night sweats, and rigors.
• Weight loss is a possible complaint.
• Patients may report arthralgias.
• Abdominal, chest, or back pain may be caused by a visceral abscess.
• Patients may have history of shunt placement for hydrocephalus, or they may have a vascular graft that has become infected.
• Patients with hepatitis B or C may have a history of intravenous drug abuse, needle stick injury, blood transfusions, or sexual promiscuity.
• Patients with HIV infection may have history of intravenous drug abuse, hemophilia, history of blood transfusion from 1977-1985, unprotected sex with multiple partners, or tuberculosis.

Physical

• Hypertension may be due to renal failure.
• Edema due to nephrotic syndrome is unusual but can develop in as many as 30% of cases associated with shunt nephritis.
• Rash may be maculopapular or purpuric.
• Lymphadenopathy is a reported finding.
• Patients may have hepatosplenomegaly.
• Findings of subacute bacterial endocarditis (SBE) may include the following:
• • Heart murmur
  • Purpura
  • Roth spots
  • Janeway lesions

Causes

Infections with bacteria, viruses, protozoa, and helminths can cause postinfectious GN (PIGN).

• Bacterial endocarditis: PIGN occurs more commonly in subacute rather than acute endocarditis. S aureus is now the most common pathogen recognized.
• Shunt nephritis: This may be associated with ventriculovascular, ventriculoperitoneal, peritoneovascular, or vascular shunts.
• Visceral abscesses: These may occur with abdominal, pulmonary, or retroperitoneal abscesses.
• Syphilis
• Hepatitis B
• Hepatitis C
• Human immunodeficiency virus
• Cytomegalovirus
• Parvovirus B19
• Hantavirus
• Malaria
• Schistosomiasis
• Leishmaniasis
• Filariasis
• Hydatid disease
• Toxoplasmosis
• Aspergillosis

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Type 1 membranoproliferative GN other than that due to infectious causes
Mixed cryoglobulinemia
Atheroembolic disease and hemolytic uremic syndrome: These are examples of nonimmune complex–mediated diseases that may mimic GN.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• Urinalysis: This may reveal hematuria, pyuria, red blood cell casts, and proteinuria. Findings are very helpful for determining if GN is primarily of a nephrotic or nephritic type.
• CBC count: The neutrophil count may be elevated in patients with an acute bacterial infection. Eosinophilia may be observed in patients with GN associated with SBE or a parasitic infection. Depending on the duration of disease and severity of renal dysfunction, anemia may be observed due to chronic kidney disease.
• BUN and creatinine: BUN and serum creatinine levels are commonly elevated in patients with infection-related GN. However, levels may be normal early in the course of these disorders.
• Electrolytes: Hyperkalemia or evidence of metabolic acidosis may be observed if the patient presents with chronic renal insufficiency.
• Liver function tests: The aspartate aminotransferase level is commonly elevated in patients with hepatitis-associated GN.
• Rheumatoid factor: The results commonly are positive in patients with GN associated with bacterial endocarditis.
• Serum complement levels (C3, C4, CH50): Complement levels commonly are low in patients with infection-related GN, more so in those with certain diseases. Low complement levels indicate an immune complex disease and are not necessarily diagnostic because they can be present in patients with other immune complex diseases (eg, lupus nephritis).
• Hepatitis panel (hepatitis B surface antigen, hepatitis C antibody): Hepatitis is a common cause of infection-related GN.
• Cryoglobulins: These are commonly present in patients who have GN associated with hepatitis C.
• VDRL test: Findings are positive in patients with GN associated with syphilis.
• HIV testing: This should be performed on all patients with GN and risk factors for HIV infection.
• Viral titers (cytomegalovirus, parvovirus B19, mumps, varicella, Epstein-Barr virus, Hantavirus): Depending on the clinical presentation, drawing blood for viral titers may be important in order to help identify the cause of the GN.
• Stool for ova and parasites: This should be performed if the patient has been in areas endemic to diseases such as schistosomiasis or filariasis.
• Antistreptolysin-O titer, antineutrophil cytoplasmic antibodies, antiglomerular basement membrane antibody, serum protein electrophoresis, and urine protein electrophoresis: Depending on the clinical presentation, these tests may be performed as part of the evaluation to help identify the cause of the GN.
• Other evaluations: In appropriate clinical circumstances, peripheral blood smears to test for malaria may be helpful.

Imaging Studies

• Renal ultrasound: This is routinely obtained in patients presenting with abnormal renal function to help rule out obstructive causes of nephropathy, and findings demonstrate certain anatomic abnormalities. It is also useful to confirm the presence of 2 functioning kidneys prior to performing percutaneous renal biopsy.
• CT scan of the chest, abdomen, or pelvis: This may be indicated if visceral abscess is suggested.
• Echocardiogram: A transthoracic echocardiogram should be performed if bacterial endocarditis is a possible cause. If findings are inconclusive, a transesophageal echocardiogram is indicated to help rule out valvular vegetations.

Procedures

• Kidney biopsy and other biopsies: These may be helpful depending on the clinical presentation.

Histologic Findings

Depending on the cause, a number of different renal lesions may be seen, as follows:

• Syphilis - Membranous or diffuse proliferative GN
• Hepatitis B - Membranous, membranoproliferative, or mesangial proliferative GN
• Hepatitis C - Membranoproliferative GN (most common), membranous GN (also seen)
• HIV - Focal segmental glomerulosclerosis (classic lesion), membranoproliferative GN or minimal change disease (less common)
• Parvovirus B19 - Focal segmental glomerulosclerosis
• Hantavirus - Mesangial GN
• Schistosomiasis - Mesangial proliferative GN, focal segmental glomerulosclerosis, membranoproliferative GN, or membranous GN
• Leishmaniasis - Mesangial or focal proliferative GN
• Hydatid - Mesangiocapillary GN, membranous GN
• Toxoplasmosis - Mesangioproliferative GN

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical Care

In most cases, the treatment of GN associated with infection is based on treating the underlying infection. In certain instances, immunosuppressive agents such as corticosteroids may be employed to reduce glomerular inflammation.

• Viral
• • Chronic hepatitis B: Treatment is indicated if associated liver dysfunction is present. The usual regimen is interferon alfa-2b at 5 million U/d for 4 months or 10 million U 3 times a week for 4 months. The efficacy of pegylated interferon in regard to hepatitis B related renal disease is unclear at this time. Lamivudine can also be used.
  • Chronic hepatitis C: Treatment is with recombinant human interferon alfa at 3 million U 3 times a week for 24 weeks. The pegylated form is long acting and slightly more effective. Preferably, interferon is given along with ribavirin, but this cannot be given in the presence of renal insufficiency.
  • HIV: Highly active antiretroviral therapy (HAART) is the standard of care for patients with HIV, with or without nephropathy. Treatment is based on findings from viral titers, the history of previous therapy, and, preferably on the advice of an infectious diseases specialist. There is evidence that HAART therapy may slow the progression of HIV associated nephropathy to end-stage renal disease.
  • Other viral agents: Cytomegalovirus, parvovirus, and polyomavirus associated nephropathy are observed in immunocompromised individuals and those who have undergone renal transplantation. Treatment is with specific antiviral agents (ie, ganciclovir for cytomegalovirus and cidofovir for polyomavirus [JC and BK virus]) and temporary withdrawal of immunosuppression therapy.
• Syphilis: Nephropathy is usually observed in secondary syphilis because this phase is associated with high levels of immune complexes. If CNS or ocular involvement is not present, treatment is similar to primary syphilis (ie, single IM dose of benzathine penicillin 2.4 million U). If the patient is allergic to penicillin, use doxycycline (100 mg PO bid) or erythromycin (500 mg PO qid) for 2 weeks.
• Endocarditis: Treatment of shunt infections and visceral abscesses is usually is based on culture sensitivity results.
• Paracytic
• • Malaria: Even though falciparum malaria can cause acute tubular necrosis due to acute hemolysis, hypotension chronic-progressive nephropathy is observed with Plasmodium malariae infection. In comparison with falciparum malaria, P malariae infection is a more indolent form of infection, which affects only 25% of erythrocytes and tends to cause chronic progressive immune complex–mediated nephropathy. Treatment with chloroquine is effective for P malariae infection because resistance is uncommon. However, treatment of the infection does not usually slow the progression of nephropathy, and most patients progress to end-stage renal disease in 3-5 years.
  • Schistosomiasis: Usually, treatment with praziquantel does not slow the progression of nephropathy. Sometimes, if schistosomiasis is associated with co-infection with Salmonella species, treatment of the Salmonella infection improves the nephropathy.
  • Others: Agents used in leishmaniasis treatment include antimony compounds (eg, sodium stibogluconate) and amphotericin B, pentamidine, and paromomycin. Diethylcarbamazepine and ivermectin are used for treating filariasis.
• Fungal: For aspergillosis, treatment is based on the site of infection and usually includes amphotericin.

Surgical Care

If bacterial endocarditis or a shunt infection does not respond to antibiotics, then surgical intervention is indicated.

Consultations

• Consultation with a nephrologist is indicated in patients with GN associated with infection.
• Consultation with an infectious diseases specialist may be appropriate if the infectious etiology is unclear.

Diet

• Salt restriction for is indicated for patients with hypertension.

Activity

• Activity can be performed as tolerated by the patient.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Antibiotic, antiprotozoal, antiviral, or antifungal agents are used, depending on the cause of infection.

Drug Category: Antibiotics

Therapy must be comprehensive and should cover all likely pathogens in the context of this clinical setting.

Drug Category: Interferons

Naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Used for treating hepatitis B and hepatitis C.

Drug Category: Anthelmintics

Parasite biochemical pathways are sufficiently different from the human host to allow selective interference by chemotherapeutic agents in relatively small doses.

Drug Category: Antiviral agents

These agents are nucleoside analogs that inhibit viral replication.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• Inpatient care depends on the severity of infection, and the need for hospitalization depends on the clinical condition of the patient (eg, the patient may require dialytic support or IV fluids and antibiotics).

Further Outpatient Care

• Oral antibiotics can be continued in an outpatient setting, with frequent monitoring of kidney function. Outpatient dialysis, if necessary, may need to be arranged.

In/Out Patient Meds

• Oral antibiotics can be continued in an outpatient setting.

Complications

• Deterioration of kidney function may require dialytic support.

Prognosis

• Complete recovery occurs in most patients, even those patients with crescents observed in kidney biopsy tissue.
• The outcome is based on the duration of infection before specific antibacterial or other antiinfective therapy is initiated.
• In schistosomal infections, progression of renal disease is common, even after treatment.
• Nephrotic-range proteinuria may persist for 6 months. A mild increase in protein excretion may be present in 15% of patients at 3 years and in 2-7% of patients at 10 years.
• Microscopic hematuria may persist for 3-6 months after resolution of the syndrome.

Patient Education

• For excellent patient education resources, visit eMedicine's Hepatitis Center, Liver, Gallbladder, and Pancreas Center, and Kidneys and Urinary System Center. Also, see eMedicine's patient education articles Hepatitis B, Hepatitis C, and Blood in the Urine.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to accurately diagnose

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Barsoum R. The changing face of schistosomal glomerulopathy. Kidney Int. Dec 2004;66(6):2472-84.
• Chadban SJ, Atkins RC. Glomerulonephritis. Lancet. May 21-27 2005;365(9473):1797-806.
• Conlon PJ, Jefferies F, Krigman HR, et al. Predictors of prognosis and risk of acute renal failure in bacterial endocarditis. Clin Nephrol. Feb 1998;49(2):96-101. [Medline].
• Haffner D, Schindera F, Aschoff A, et al. The clinical spectrum of shunt nephritis [see comments]. Nephrol Dial Transplant. Jun 1997;12(6):1143-8. [Medline].
• Jefferson JA, Johnson RJ. Treatment of hepatitis C-associated glomerular disease. Semin Nephrol. May 2000;20(3):286-92. [Medline].
• Lu TC, Ross M. HIV-associated nephropathy: a brief review. Mt Sinai J Med. May 2005;72(3):193-9.
• Sorger K. Postinfectious glomerulonephritis. Subtypes, clinico-pathological correlations, and follow-up studies. Veroff Pathol. 1986;DA - 19870219:1-105. [Medline].
• Tang S, Lai FM, Lui YH. Lamivudine in hepatitis B-associated membranous nephropathy. Kidney Int. Oct 2005;68(4):1750-8.

Article Last Updated: May 22, 2006