Rapidly progressive glomerulonephritis overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Jogeet Singh Sekhon, M.D. [2] Nazia Fuad M.D.
Overview
Rapidly progressive glomerulonephritis (RPGN) is a disease of kidney which occurs following severe damage to the kidneys and it can lead to rapid deterioration of kidney function in a few days. It is characterized by the presence of crescents in the glomeruli and hence is also called crescentic glomerulonephritis. Patients with RPGN present with nephritic syndrome, but some may also have proteinuria. RPGN progresses to end stage renal disease if it is not treated in time. RPGN is classified into three types, all of which involve immune-mediated damage to the glomeruli. In type I RPGN, injury is caused by antibodies directed against the glomerular basement membrane. Type II RPGN is characterized by the deposition of immune complexes in the glomerulus. Type III, or pauci-immune RPGN, features antibodies directed against neutrophils (anti-neutrophil cytoplasmic antibodies, ANCA). Treatment depends on the underlying disease process. For example, plasmapheresis, corticosteroids, and cytotoxic drugs may promote recovery in Goodpasture syndrome, a cause of type I RPGN. Despite even early treatment, however, many patients with RPGN may ultimately require dialysis and possibly renal transplant.
Historical Perspective
1919 Ernst Goodpasture made case reports about glomerulnophritis and pulmonary haemorrhage. Stanton and Tait from Australia studied these case reports and then named the findings as Goodpasture syndrome in 1958. They gave the anti GBM antibodies classification and discovered RPGN in these cases. In 1960s electron microscopy and immunofluorescence helped to learn RPNG on immunological level.
Classification
Rapidly progressive glomerulonephritis can be classified on the basis of cause of glomerular injury.The immunoflourescent microspcopic findings are used in determining the cause of glomerular injury.
Pathophysiology
Rapidly progressive glomerulonephritis is a disease of the kidney in which the renal function deteriorates in a few days. Atleast 50% reduction in GFR occurs in RPGN in a few days to weeks. RPGN occurs from severe and fast damage to the GBM which results in crescent formation, the main pathological finding in RPGN. Injury can occur by anti GBM antibodies-type I RPGN, Immune complex- type II RPGN or pauci immune RPGN(ANCAs)-type III RPGN. Crescents are present in the Bowmans space. Light, immunofluoresnce and electron microscopy are used to diagnose RPGN.
Causes
Rapidly progressive glomerulonephritis can be caused by multiple factors.These include life threatening conditions such as sepsis and other preexisting renal diseases. Infections, drugs and some types of cancer also cause RPGN.
Differentiating rapildy progressive glomerulonephritis from Other Diseases
The various types of glomerulonephritides should be differentiated from each other based on associations, presence of pitting edema, hemeturia, hypertension, hemoptysis, oliguria, peri-orbital edema, hyperlipidemia, type of antibodies, light and electron microscopic features.
Epidemiology and Demographics
The incidence of RPGN is 1 per 1 million individuals per year and the incidence is affected by race and age.
Risk Factors
Common risk factors in the development of rapidly progressive glomerulonephritis may be occupational, environmental, genetic, and viral.
Screening
There is insufficient evidence to recommend routine screening for rapidly progressive glomerulonephritis.
Natural History, Complications, and Prognosis
Patients with RPGN present with flu like symptoms initially and then develop nephritic syndrome with proteinuria in some cases as well. In type III RPGN, systemic features of vasculitis are present in some cases.Pulmonary symptoms are also present in Goodpastures syndrome and Churg Strauss syndrome.The prognosis is usually poor due to rapid deterioration of renal function and is dependent on age, presence of pulmonary symptoms, serum creatinine levels and presence of ANCAs.
Diagnosis
Diagnostic Study of Choice
Determination of ANCAs can aid in the diagnosis, but positivity is not conclusive and negative ANCAs are not sufficient to reject the diagnosis. Cytoplasmic staining ANCAs that react with the enzyme proteinase 3 (cANCA) in neutrophils (a type of white blood cell) are associated with Granulomatosis with polyangiitis. If the patient has renal failure or cutaneous vasculitis, these are the most logical organs to obtain a biopsy from. Rarely, thoracoscopic lung biopsy is required.
History and Symptoms
In rapidly progressive glomerulonephritis The most common early presentation is flulike symptoms characterized by malaise, fever, arthralgias, myalgias, anorexia, and weight loss. This is seen in more than 90% of patients. Following the initial phase, the other symptoms include abdominal pain, painful cutaneous nodules or ulcerations, and a migratory polyarthropathy. When pulmonary or upper airway involvement is present, patients complain of sinusitis symptoms, cough, and hemoptysis
Physical Examination
Common physical examination findings of rapidly progressive glomerulonephritis include, hematuria, hypertension, edema, skin nodules, gastrointestinal bleeding.
Arthralgia and arthritis may be seen. Nervous system involvement is present in 30% of patients with microscopic polyangiitis and 70% of patients with Churg-Strauss diseas.
Laboratory Findings
The most important step in managing rapidly progressive glomerulonephritis is rapid diagnosis. It is essential for organ preservation. Laboratory studies include, complete blood cell count (CBC) with differential, serum electrolytes, BUN, creatinine, lactate dehydrogenase (LDH), creatine phosphokinase (CPK), and liver function tests: The most common abnormality is an increased serum creatinine level. However, the level can be normal at presentation. Tissue enzyme (ie, LDH, CPK) levels may be elevated if there is significant muscle inflammation and myalgias. Urinalysis with microscopy usually show proteinuria but is rarely greater than 2-3 g in 24 hours. Microscopic hematuria may be present and may be the only clue to renal disease at presentation. The presence of red cell casts indicates glomerulonephritis and is a very helpful clue. Erythrocyte sedimentation rate is usually elevated with active disease. C-reactive protein levels are elevated and correspond with disease activity. High antinuclear antibody (ANA) titer rises the suspicion toward systemic lupus erythematosus. More than 80% of patients with microscopic polyangiitis are ANCA-positive. The symptoms of cryoglobulinemia are very similar to those of ANCA-related disease. However, in persons with ANCA-related diseases, the cryoglobulin titer result should be negative. Hepatitis profile should be performed as hepatitis B is associated with polyarteritis nodosa and hepatitis C is associated with mixed cryoglobulinemia. Urine and serum protein electrophoresis is done in any middle-aged or elderly person presenting with rapidly progressive glomerulonephritis to exclude the presence of light-chain disease or noticeable multiple myeloma as a cause of the clinical findings
Electrocardiogram
There are no EKG findings associated with rapidly progressive glomerulonephritis
X-ray
There are no x-ray findings associated with rapidly progressive glomerulonephritis unless it is associated with anti-GBM antibody disease (Goodpasture syndrome). On chest X-ray, Goodpasture syndrome is characterized by parenchymal consolidations that are most often present in both lungs, perihilar, and bibasilar. When pulmonary hemorrhage is recurrent an interstitial pattern is observed
Echocardiography and Ultrasound
There are no EKG findings associated with rapidly progressive glomerulonephritis
Kidney ultrasound is usually done during the diagnostic biopsy. Due to its rapid progression, the renal biopsy usually shows normal-sized kidneys. Although the test is not diagnostic, its non-invasive nature and the necessity to rule out other etiologies of renal impairment are both in favor of performing a renal ultrasound
CT scan
There are no CT scan findings associated with rapidly progressive glomerulonephritis.
MRI
There are no MRI findings associated with rapidly progressive glomerulonephritis.
Other Imaging Findings
There are no other imaging findings associated with rapidly progressive glomerulonephritis
Other Diagnostic Studies
The sensitivity and the specificity of ANCA testing for pauci-immune glomerulonephritis is only 80-90%, a renal biopsy is crucial for diagnosis of rapidly progressive glomerulonephritis. It helps to determine the severity of the disease. The initiation of therapy should not be delayed for biopsy results. Renal biopsy specimens show a diffuse, proliferation, necrotizing glomerulonephritis with crescent formation. Immunofluorescence microscopy shows finding of linear deposition of immunoglobulin G (IgG) along the glomerular capillaries and occasionally the distal tubules.
Treatment
Medical Therapy
Treatment of RPGN depends on the underlying disease process. For example, plasmapheresis, corticosteroids, and cytotoxic drugs may promote recovery in Goodpasture syndrome, a cause of type I RPGN. Despite even early treatment, however, many patients with RPGN may ultimately require dialysis and possibly renal transplant.
Surgery
Surgery is not the first-line treatment option for patients with rapidly progressive glomerulonephritis. Renal transplantation is usually reserved for patients who present with undetectable circulating anti-glomerular basement antibodies in serum for 12 months and at least 6 months after stopping the use of cytotoxic agents.
Primary Prevention
There are no established measures for the primary prevention of Rapidly progressive glomerulonephritis.
Secondary Prevention
There are no established measures for the secondary prevention of Rapidly progressive glomerulonephritis.