Acute glomerulonephritis (AGN)

Definition:
is active inflammation in the glomeruli. Each kidney is composed of about 1 million microscopic filtering "screens" known as glomeruli that selectively remove uremic waste products. The inflammatory process usually begins with an infection or injury (e.g., burn, trauma), then the protective immune system fights off the infection, scar tissue forms, and the process is complete. There are many diseases that cause an active inflammation within the glomeruli. Some of these diseases are systemic (i.e., other parts of the body are involved at the same time) and some occur solely in the glomeruli. When there is active inflammation within the kidney, scar tissue may replace normal, functional kidney tissue and cause irreversible renal impairment. The severity and extent of glomerular damagefocal (confined) or diffuse (widespread) determines how the disease is manifested. Glomerular damage can appear as subacute renal failure, progressive chronic renal failure (CRF); or simply a urinary abnormality such as hematuria (blood in the urine) or proteinuria (excess protein in the urine).

History

A thorough history should focus on the identification of an underlying systemic disease (if any) or recent infection. Most often, the patient is a boy, aged 2-14 years, who suddenly develops puffiness of the eyelids and facial edema in the setting of a poststreptococcal infection. The urine is dark and scanty, and the blood pressure may be elevated. Onset of symptoms is usually abrupt. Nonspecific symptoms include weakness, fever, abdominal pain, and malaise. In the setting of a postinfectious acute nephritis, a latent period of up to 3 weeks occurs before onset of symptoms. However, the latent period may vary; typically 1-2 weeks for postpharyngitis cases and 2-4 weeks for cases of postdermal infection (ie, pyoderma). Onset of nephritis within 1-4 days of streptococcal infection suggests preexisting renal disease. Symptoms of acute glomerulonephritis include the following: Hematuria is a universal finding, even if it is microscopic. Gross hematuria is reported in 30% of pediatric patients. Oliguria Edema (peripheral or periorbital) is reported in approximately 85% of pediatric patients; edema may be mild (involving only the face) to severe, bordering on a nephrotic appearance. Headache may occur secondary to hypertension; confusion secondary to malignant hypertension may be seen in as many as 5% of patients. Shortness of breath or dyspnea on exertion secondary to heart failure or pulmonary edema; usually uncommon, particularly in children. Possible flank pain secondary to stretching of the renal capsule.

Patients may also present with symptoms specific to an underlying systemic disease that can precipitate an acute glomerulonephritis. These disease entities are briefly described in Causes. Classic presentations include the following: Triad of sinusitis, pulmonary infiltrates, and nephritis suggesting Wegener granulomatosis Nausea/vomiting, abdominal pain, and purpura observed with Henoch-Schnlein purpura Arthralgias associated with systemic lupus erythematosus (SLE) Hemoptysis occurring with Goodpasture syndrome or idiopathic progressive glomerulonephritis Skin rashes observed with a hypersensitivity vasculitis or systemic lupus erythematosus; also possibly due to the purpura that can occur in hypersensitivity vasculitis, cryoglobulinemia, and Henoch-Schnlein purpura

Causes In diffuse glomerulonephritis (GN), all of the glomeruli are aggressively attacked, leading to acute renal failure (ARF). Disorders that attack several organs and cause diffuse GN are referred to as secondary causes. Secondary causes of diffuse GN include the following:

Cryoglobulinemia Goodpasteurs syndrome (membranous antiglomerular basement membrane disease) Lupus nephritis Schnlein-Henoch purpura Vasculitis (e.g., Wegener's granulomatosis, periarteritis nodosa)

Primary diseases that solely affect the kidneys and cause AGN, include the following:

Immunoglobulin A nephropathy (IgA nephropathy, Bergers disease) Membranoproliferative nephritis (type of kidney inflammation) Postinfectious GN (GN that results after an infection)

Causes
Causes of acute glomerulonephritis include postinfectious, renal, and systemic etiologies. Each is described briefly.

Postinfectious etiologies o The most common cause is postinfectious Streptococcus species (ie, group A, beta-hemolytic). Two types have been described as (1) attributed to serotype 12, poststreptococcal nephritis due to an upper respiratory infection occurring primarily in the winter months, and (2) attributed to serotype 49, poststreptococcal nephritis due to a skin infection usually observed in the summer and fall and more prevalent in southern regions of the United States.

Other specific agents include viruses and parasites, systemic and renal disease, visceral abscesses, endocarditis, infected grafts or shunts, and pneumonia. o Bacterial causes other than group A streptococci may be diplococcal, streptococcal, staphylococcal, or mycobacterial. Salmonella typhosa, Brucella suis, Treponema pallidum, Corynebacterium bovis, and actinobacilli have also been identified. 2 o Cytomegalovirus, coxsackievirus, Epstein-Barr virus, hepatitis B, rubella, rickettsial scrub typhus, and mumps are accepted as viral causes only if it can be documented that a recent group A beta-hemolytic streptococcal infection did not occur. Acute glomerulonephritis has been documented as a rare complication of hepatitis A.3 o Fungal and parasitic: Attributing glomerulonephritis to a parasitic or fungal etiology requires the exclusion of a streptococcal infection. Identified organisms include Coccidioides immitis and the following parasites: Plasmodium malariae, Plasmodium falciparum, Schistosoma mansoni, Toxoplasma gondii, filariasis, trichinosis, and trypanosomes. Systemic causes o Vasculitis (ie, Wegener granulomatosis causes glomerulonephritis that combines upper and lower granulomatous nephritides). o Collagen vascular diseases (ie, systemic lupus erythematosus causes glomerulonephritis through renal deposition of immune complexes). o Hypersensitivity vasculitis encompasses a heterogeneous group of disorders featuring small vessel and skin disease. o Cryoglobulinemia causes abnormal quantities of cryoglobulin in plasma that result in repeated episodes of widespread purpura and cutaneous ulcerations upon crystallization. o Polyarteritis nodosa causes nephritis from a vasculitis involving the renal arteries. o Henoch-Schnlein purpura causes a generalized vasculitis resulting in glomerulonephritis. o Goodpasture syndrome causes circulating antibodies to type IV collagen and often results in a rapidly progressive oliguric renal failure (weeks to months). o Drug-induced (ie, gold, penicillamine) Renal diseases o Membranoproliferative glomerulonephritis is due to the expansion and proliferation of mesangial cells as a consequence of the deposition of complements. o Type I refers to the granular deposition of C3; type II refers to an irregular process. o Berger disease (IgG-immunoglobulin A [IgA] nephropathy) glomerulonephritis results from a diffuse mesangial deposition of IgA and IgG. o Idiopathic rapidly progressive glomerulonephritis is a form of glomerulonephritis characterized by the presence of glomerular crescents. Three types have been distinguished. Type I is an antiglomerular basement membrane disease, type II is mediated by immune complexes, and type III is identified by antineutrophil cytoplasmic antibody.

Signs and Symptoms Patients who have secondary causes of AGN often exhibit these symptoms:

Cough with blood-tinged sputum Fever Joint or muscle pain Rash

Diagnosis Patients with acute glomerulonephritis (AGN) have an active urinary sediment. This means that signs of active kidney inflammation can be detected when the urine is examined under the microscope. Such signs include red blood cells, white blood cells, proteinuria (blood proteins in the urine), and "casts" of cells that have leaked through the glomeruli and have reached the tubule, where they develop into cylindrical forms. A kidney biopsy is essential to establish a diagnosis of AGN, determine the cause, and create an effective treatment plan. Treatment The goal of treatment is to stop the ongoing inflammation and lessen the degree of scarring that ensues. Depending on the diagnosis, there are different treatment strategies. Often the treatment warrants a regimen of immunosuppressive drugs to limit the immune systems activity. This decreases the degree of inflammation and subsequent irreversible scarring.

Pathophysiology
Glomerular lesions in acute glomerulonephritis are the result of glomerular deposition or in situ formation of immune complexes. On gross appearance, the kidneys may be enlarged up to 50%. Histopathologic changes include swelling of the glomerular tufts and infiltration with polymorphonucleocyte. Immunofluorescence reveals deposition of immunoglobulins and complement. With the exception of poststreptococcal glomerulonephritis, the exact triggers for the formation of the immune complexes are unclear. In streptococcal infection, involvement of derivatives of streptococcal proteins has been reported. A streptococcal neuraminidase may alter host immunoglobulin G (IgG). IgG combines with host antibodies. IgG/anti-IgG immune complexes are formed and then collect in the glomeruli. In addition, elevations of antibody titers to other antigens, such as antistreptolysin O or antihyaluronidase, DNAase-B, and streptokinase, provide evidence of a recent streptococcal infection.