Rapidly progressive glomerulonephritis

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Rapidly progressive glomerulonephritis
Other namesCrescentic glomerulonephritis [1]
Crescentic glomerulonephritis (2).jpg
Histopathological image of crescentic glomerulonephritis in a patient with MPO-ANCA positive rapid progressive glomerulonephritis. Hematoxylin & eosin stain.
Specialty Nephrology
Symptoms Hematuria [2]
TypesType I, II and III [3]
Diagnostic method Serum analysis [2]
TreatmentCorticosteroids

Rapidly progressive glomerulonephritis (RPGN) is a syndrome of the kidney that is characterized by a rapid loss of kidney function, [4] [5] (usually a 50% decline in the glomerular filtration rate (GFR) within 3 months) [5] with glomerular crescent formation seen in at least 50% [5] or 75% [4] of glomeruli seen on kidney biopsies. If left untreated, it rapidly progresses into acute kidney failure [6] and death within months. In 50% of cases, RPGN is associated with an underlying disease such as Goodpasture syndrome, systemic lupus erythematosus or granulomatosis with polyangiitis; the remaining cases are idiopathic. Regardless of the underlying cause, RPGN involves severe injury to the kidneys' glomeruli, with many of the glomeruli containing characteristic glomerular crescents (crescent-shaped scars). [7]

Contents

Signs and symptoms

Most types of RPGN are characterized by severe and rapid loss of kidney function with marked hematuria; red blood cell casts in the urine; and proteinuria sometimes exceeding three grams in twenty-four hours, a range associated with nephrotic syndrome. Some patients also experience hypertension and edema. Severe disease is characterized by pronounced oliguria or anuria, which portends a poor prognosis. [2]

Pathophysiology

P anca.jpg

It is thought that antineutrophil cytoplasmic antibodies (ANCA) interact with antigens in the cytoplasm of neutrophils to cause an early[ citation needed ] degranulation, triggering the release of lytic enzymes at the site of injury [8] and leading to the formation of glomerular crescents that consist primarily of parietal epithelial cells from Bowman's capsule and in some cases podocytes. [9]

Diagnosis

Serum analysis often aids in the diagnosis of a specific underlying disease. The presence of anti-glomerular basement membrane (GBM) antibodies suggests type I RPGN; antinuclear antibodies (ANA) may support a diagnosis of systemic lupus erythematosus and type II RPGN; and type III and idiopathic RPGN are frequently associated with anti-neutrophil cytoplasmic antibodies (ANCA)-positive serum. [2]

Impaired kidney function in an individual who has had the condition for fewer than three months is characteristic of RPGN. An ultrasonographic examination of the abdomen should be obtained. Although the presence of sediment in the urine on examination can indicate proliferative glomerulonephritis, many cases of rapidly progressive glomerulonephritis need a renal biopsy to make a diagnosis. [10]

Classification

Crescentic glomerulonephritis Crescentic glomerulonephritis (1).jpg
Crescentic glomerulonephritis

RPGN can be classified into three types, based upon the immunofluorescence patterns: [3]

Type I

Accounting for approximately 3 [11] % of RPGN, type I RPGN, also called anti-GBM glomerulonephritis, is characterized by the presence of autoantibodies directed against type IV collagen (specifically, the noncollagenous region of its α3 chain) [2] in the glomerular basement membrane (GBM). Some cases are associated with antibodies directed against the basement membrane of lung alveoli, producing Goodpasture syndrome. The majority of type I disease, however, features anti-GBM antibodies alone; these cases are considered idiopathic. [2]

Type II

Characterized by deposition of immune complexes in glomerular tissues, type II RPGN accounts for 40 [11] % of cases. Any immune complex disease—including systemic lupus erythematosus, acute proliferative glomerulonephritis, Henoch–Schönlein purpura, and IgA nephropathy—that involves the glomerulus may progress to RPGN if severe enough. [2]

Type III

Also known as pauci-immune RPGN, type III RPGN accounts for 55% of RPGN and features neither immune complex deposition nor anti-GBM antibodies. Instead, the glomeruli are damaged in an undefined manner, perhaps through the activation of neutrophils in response to ANCA. Type III RPGN may be isolated to the glomerulus (primary, or idiopathic) or associated with a systemic disease (secondary). In most cases of the latter, the systemic disease is an ANCA-associated vasculitis such as granulomatosis with polyangiitis, microscopic polyangiitis or eosinophilic granulomatosis with polyangiitis. [2]

Treatment

Therapy consists of a combination of rituximab, [12] corticosteroids, and cyclophosphamide, with a substitution of azathioprine for cyclophosphamide after a ninety-day initial period being another option. [12] When remission is achieved, immunosuppressants are still used, [13] usually corticosteroids with azathioprine or rituximab infusions. [13]

Epidemiology

The incidence rate of rapidly progressive glomerulonephritis is approximately 3.9 individuals per million. [14]

Related Research Articles

<span class="mw-page-title-main">Nephrotic syndrome</span> Symptoms resulting from kidney damage

Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy urine. Complications may include blood clots, infections, and high blood pressure.

<span class="mw-page-title-main">Nephritis</span> Inflammation of the kidneys

Nephritis is inflammation of the kidneys and may involve the glomeruli, tubules, or interstitial tissue surrounding the glomeruli and tubules. It is one of several different types of nephropathy.

<span class="mw-page-title-main">Vasculitis</span> Medical disorders that destroy blood vessels by inflammation

Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis. Vasculitis is primarily caused by leukocyte migration and resultant damage. Although both occur in vasculitis, inflammation of veins (phlebitis) or arteries (arteritis) on their own are separate entities.

<span class="mw-page-title-main">Granulomatosis with polyangiitis</span> Medical condition

Granulomatosis with polyangiitis (GPA), previously known as Wegener's granulomatosis (WG), after the German physician Friedrich Wegener, is a rare long-term systemic disorder that involves the formation of granulomas and inflammation of blood vessels (vasculitis). It is an autoimmune disease and a form of vasculitis that affects small- and medium-size vessels in many organs but most commonly affects the upper respiratory tract, lungs and kidneys. The signs and symptoms of GPA are highly varied and reflect which organs are supplied by the affected blood vessels. Typical signs and symptoms include nosebleeds, stuffy nose and crustiness of nasal secretions, and inflammation of the uveal layer of the eye. Damage to the heart, lungs and kidneys can be fatal.

<span class="mw-page-title-main">Eosinophilic granulomatosis with polyangiitis</span> Medical condition

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as allergic granulomatosis, is an extremely rare autoimmune condition that causes inflammation of small and medium-sized blood vessels (vasculitis) in persons with a history of airway allergic hypersensitivity (atopy).

<span class="mw-page-title-main">Glomerulonephritis</span> Term for several kidney diseases

Glomerulonephritis (GN) is a term used to refer to several kidney diseases. Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component.

<span class="mw-page-title-main">Anti-neutrophil cytoplasmic antibody</span> Group of autoantibodies

Anti-neutrophil cytoplasmic antibodies (ANCAs) are a group of autoantibodies, mainly of the IgG type, against antigens in the cytoplasm of neutrophils and monocytes. They are detected as a blood test in a number of autoimmune disorders, but are particularly associated with systemic vasculitis, so called ANCA-associated vasculitides (AAV).

<span class="mw-page-title-main">Membranous glomerulonephritis</span> Kidney disease

Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people.

<span class="mw-page-title-main">Nephritic syndrome</span> Symptoms resulting from kidney inflammation

Nephritic syndrome is a syndrome comprising signs of nephritis, which is kidney disease involving inflammation. It often occurs in the glomerulus, where it is called glomerulonephritis. Glomerulonephritis is characterized by inflammation and thinning of the glomerular basement membrane and the occurrence of small pores in the podocytes of the glomerulus. These pores become large enough to permit both proteins and red blood cells to pass into the urine. By contrast, nephrotic syndrome is characterized by proteinuria and a constellation of other symptoms that specifically do not include hematuria. Nephritic syndrome, like nephrotic syndrome, may involve low level of albumin in the blood due to the protein albumin moving from the blood to the urine.

Microscopic polyangiitis is an autoimmune disease characterized by a systemic, pauci-immune, necrotizing, small-vessel vasculitis without clinical or pathological evidence of granulomatous inflammation.

<span class="mw-page-title-main">Membranoproliferative glomerulonephritis</span> Medical condition

Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating the complement system and damaging the glomeruli.

<span class="mw-page-title-main">Mesangial proliferative glomerulonephritis</span> Medical condition

Mesangial proliferative glomerulonephritis (MesPGN) is a morphological pattern characterized by a numerical increase in mesangial cells and expansion of the extracellular matrix within the mesangium of the glomerulus. The increase in the number of mesangial cells can be diffuse or local and immunoglobulin and/or complement deposition can also occur. MesPGN is associated with a variety of disease processes affecting the glomerulus, though can be idiopathic. The clinical presentation of MesPGN usually consists of hematuria or nephrotic syndrome. Treatment is often consistent with the histologic pattern of and/or disease process contributing to mesangial proliferative glomerulonephritis, and usually involves some form of immunosuppressant.

Pulmonary-renal syndrome (PRS) is a rare medical syndrome in which respiratory failure involving bleeding in the lungs and kidney failure (glomerulonephritis) occur. PRS is associated with a high rate of morbidity and death. The term was first used by Goodpasture in 1919 to describe the association of respiratory and kidney failure.

Glomerulonephrosis is a non-inflammatory disease of the kidney (nephrosis) presenting primarily in the glomerulus as nephrotic syndrome. The nephron is the functional unit of the kidney and it contains the glomerulus, which acts as a filter for blood to retain proteins and blood lipids. Damage to these filtration units results in important blood contents being released as waste in urine. This disease can be characterized by symptoms such as fatigue, swelling, and foamy urine, and can lead to chronic kidney disease and ultimately end-stage renal disease, as well as cardiovascular diseases. Glomerulonephrosis can present as either primary glomerulonephrosis or secondary glomerulonephrosis.

Pauci-immune vasculitis is a form of vasculitis that is associated with minimal evidence of hypersensitivity upon immunofluorescent staining for IgG. Often, this is discovered in the setting of the kidney.

<span class="mw-page-title-main">Systemic vasculitis</span> Medical condition

Necrotizing vasculitis, also called systemic necrotizing vasculitis, is a general term for the inflammation of veins and arteries that develops into necrosis and narrows the vessels.

Diffuse proliferative glomerulonephritis (DPGN) is a type of glomerulonephritis that is the most serious form of renal lesions in SLE and is also the most common, occurring in 35% to 60% of patients. In absence of SLE, DPGN pathology looks more like Membranoproliferative glomerulonephritis

Ronald Jonathan Falk, MD, FACP, FASN is the Nan and Hugh Cullman Eminent Professor and Chair of the Department of Medicine at the University of North Carolina-Chapel Hill (UNC). He is a clinical nephrologist and internationally recognized expert in anti-neutrophil cytoplasmic autoantibody (ANCA)-induced vasculitis and autoimmune kidney disease. His career as a translational physician-scientist spans more than three decades. His clinical practice and translational research focus on characterizing the cell, tissue and physiologic changes in the development of specific autoimmune kidney diseases and developing new approaches for studying autoimmunity, inflammation and basic neutrophil/monocyte biology. He was Chief of the UNC Division of Nephrology and Hypertension from 1993-2015. He co-founded the UNC Kidney Center in 2005 and continues as Co-Director. Falk is a Past-President of the American Society of Nephrology (ASN). Since 2015, he has served as Chair of the Department of Medicine at UNC.

<span class="mw-page-title-main">IgM nephropathy</span> Medical condition

IgM nephropathy or immunoglobulin M nephropathy (IgMN) is a kind of idiopathic glomerulonephritis that is marked by IgM diffuse deposits in the glomerular mesangium. IgM nephropathy was initially documented in 1978 by two separate teams of researchers.

<span class="mw-page-title-main">J. Charles Jennette</span> Doctor, academic, and author

J. Charles Jennette is a physician, nephropathologist, academic, and author. He served as Kenneth M. Brinkhous Distinguished Professor and Chair of Pathology and Laboratory Medicine at the University of North Carolina at Chapel Hill School of Medicine, and Chief of Pathology and Laboratory Medicine Services at UNC Hospitals from 1999 to 2019.

References

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  6. "rapidly progressive glomerulonephritis" at Dorland's Medical Dictionary
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  10. Bhowmik, Dipankar (January 2011). "Clinical Approach to Rapidly Progressive Renal Failure" (PDF). Journal of the Association of Physicians of India. 59: 38–41. PMID   21751663 . Retrieved 31 October 2015.
  11. 1 2 "Table:Classification of Rapidly Progressive Glomerulonephritis Based on Immunofluorescence Microscopy". MSD Manual Professional Edition.
  12. 1 2 Greenhall, George H.B.; Salama, Alan D. (2015). "What is new in the management of rapidly progressive glomerulonephritis?". Clinical Kidney Journal. 8 (2): 143–150. doi:10.1093/ckj/sfv008. ISSN   2048-8505. PMC   4370308 . PMID   25815169.
  13. 1 2 Jennette, J. Charles; Nachman, Patrick H. (2017-10-06). "ANCA Glomerulonephritis and Vasculitis". Clinical Journal of the American Society of Nephrology. 12 (10): 1680–1691. doi: 10.2215/CJN.02500317 . ISSN   1555-9041. PMC   5628710 . PMID   28842398.
  14. Hedger, Neil; Stevens, Judith; Drey, Nick; Walker, Sarah; Roderick, Paul (2000-10-01). "Incidence and outcome of pauci‐immune rapidly progressive glomerulonephritis in Wessex, UK: a 10‐year retrospective study". Nephrology Dialysis Transplantation. 15 (10): 1593–1599. doi: 10.1093/ndt/15.10.1593 . ISSN   0931-0509. PMID   11007827.

Further reading