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| name = Glomerulonephritis
| name = Glomerulonephritis
| image = Crescentic glomerulonephritis HE stain.JPEG
| image = Crescentic glomerulonephritis HE stain.JPEG
| caption = Photomicrograph of a [[kidney]] [[biopsy]] from a person with [[crescentic glomerulonephritis]] showing prominent fibrocellular crescent formation and moderate [[mesangium|mesangial]] proliferation in a [[glomerulus]]. [[Hematoxylin and eosin stain]].
| caption = Photomicrograph of a [[kidney]] [[biopsy]] from a person with [[crescentic glomerulonephritis]] showing prominent fibrocellular crescent formation and moderate [[mesangium|mesangial]] proliferation in a [[Glomerulus (kidney)|glomerulus]]. [[Hematoxylin and eosin stain]].
| field = [[Nephrology]]
| field = [[Nephrology]]
| pronounce =
| pronounce =
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| deaths =
| deaths =
}}
}}
'''Glomerulonephritis''' ('''GN''') is a term used to refer to several [[kidney]] diseases (usually affecting both kidneys). Many of the diseases are characterised by [[inflammation]] either of the [[glomerulus|glomeruli]] or of the small blood vessels in the kidneys, hence the name,<ref>{{DorlandsDict|four/000045097|glomerulonephritis}}</ref> but not all diseases necessarily have an inflammatory component.{{cn}}
'''Glomerulonephritis''' ('''GN''') is a term used to refer to several [[kidney]] diseases (usually affecting both kidneys). Many of the diseases are characterised by [[inflammation]] either of the [[glomerulus (kidney)|glomeruli]] or of the small blood vessels in the kidneys, hence the name,<ref>{{DorlandsDict|four/000045097|glomerulonephritis}}</ref> but not all diseases necessarily have an inflammatory component.{{cn|date=November 2023}}


As it is not strictly a single disease, its presentation depends on the specific disease entity: it may present with isolated [[hematuria]] and/or [[proteinuria]] (blood or protein in the [[urine]]); or as a [[nephrotic syndrome]], a [[nephritic syndrome]], [[acute kidney injury]], or [[chronic kidney disease]].
As it is not strictly a single disease, its presentation depends on the specific disease entity: it may present with isolated [[hematuria]] and/or [[proteinuria]] (blood or protein in the [[urine]]); or as a [[nephrotic syndrome]], a [[nephritic syndrome]], [[acute kidney injury]], or [[chronic kidney disease]].
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[[File:Gray1130.svg|thumb|left|A [[glomerulus (kidney)|glomerulus]], a functional unit that represents the first step in the filtration of [[blood]] and generation of [[urine]].]]
[[File:Gray1130.svg|thumb|left|A [[glomerulus (kidney)|glomerulus]], a functional unit that represents the first step in the filtration of [[blood]] and generation of [[urine]].]]


Glomerulonephritis refers to an inflammation of the [[glomerulus (kidney)|glomerulus]], which is the unit involved in filtration in the kidney. This inflammation typically results in one or both of the [[nephrotic syndrome|nephrotic]] or [[nephritic syndrome]]s.<ref name=DAVIDSONS2010 />{{rp|500}}
Glomerulonephritis refers to an inflammation of the [[glomerulus (kidney)|glomerulus]], which is the unit involved in filtration in the kidney. This inflammation typically results in one or both of the [[nephrotic syndrome|nephrotic]] or [[nephritic syndrome]]s.<ref name="DAVIDSONS2010" />{{rp|500}}


===Nephrotic syndrome===
===Nephrotic syndrome===
<!-- please do not move GN subtypes here, as they may result in mixed presentations -->
<!-- please do not move GN subtypes here, as they may result in mixed presentations -->
{{Main|Nephrotic syndrome}}
{{Main|Nephrotic syndrome}}
The nephrotic syndrome is characterised by the finding of [[edema]] in a person with [[proteinuria|increased protein in the urine]] and [[hypoalbuminemia|decreased protein in the blood]], with [[hyperlipidemia|increased fat in the blood]]. Inflammation that affects the cells surrounding the glomerulus, [[podocyte]]s, increases the permeability to [[protein]]s, resulting in an increase in excreted proteins. When the amount of proteins excreted in the urine exceeds the liver's ability to compensate, fewer proteins are detected in the blood – in particular [[albumin]], which makes up the majority of circulating proteins. With decreased proteins in the blood, there is a decrease in the [[oncotic pressure]] of the blood. This results in edema, as the oncotic pressure in tissue remains the same. Although decreased intravascular oncotic (i.e. osmotic) pressure partially explains the patient's edema, more recent studies have shown that extensive sodium retention in the distal nephron (collecting duct) is the predominant cause of water retention and edema in the nephrotic syndrome.<ref>The Nephrotic Syndrome
The nephrotic syndrome is characterised by the finding of [[edema]] in a person with [[proteinuria|increased protein in the urine]] and [[hypoalbuminemia|decreased protein in the blood]], with [[hyperlipidemia|increased fat in the blood]]. Inflammation that affects the cells surrounding the glomerulus, [[podocyte]]s, increases the permeability to [[protein]]s, resulting in an increase in excreted proteins. When the amount of proteins excreted in the urine exceeds the liver's ability to compensate, fewer proteins are detected in the blood – in particular [[albumin]], which makes up the majority of circulating proteins. With decreased proteins in the blood, there is a decrease in the [[oncotic pressure]] of the blood. This results in edema, as the oncotic pressure in tissue remains the same. Although decreased intravascular oncotic (i.e. osmotic) pressure partially explains the patient's edema, more recent studies have shown that extensive sodium retention in the distal nephron (collecting duct) is the predominant cause of water retention and edema in the nephrotic syndrome.<ref>{{Cite journal |vauthors=Orth SR, Ritz E |date=April 1998 |title=The nephrotic syndrome |journal=N Engl J Med |volume=338 |issue=17 |pages=1202–11 |doi=10.1056/NEJM199804233381707 |pmid=9554862}}</ref> This is worsened by the secretion of the hormone [[aldosterone]] by the adrenal gland, which is secreted in response to the decrease in circulating blood and causes [[sodium]] and [[water]] retention. [[Hyperlipidemia]] is thought to be a result of the increased activity of the liver.<ref name="ROBBINS2007" />{{rp|549}}
Stephan R. Orth, M.D., and Eberhard Ritz, M.D.
N Engl J Med 1998; 338:1202–1211 April 23, 1998 DOI: 10.1056/NEJM199804233381707</ref> This is worsened by the secretion of the hormone [[aldosterone]] by the adrenal gland, which is secreted in response to the decrease in circulating blood and causes [[sodium]] and [[water]] retention. [[Hyperlipidemia]] is thought to be a result of the increased activity of the liver.<ref name=ROBBINS2007 />{{rp|549}}


===Nephritic syndrome===
===Nephritic syndrome===
[[File:Filtration barrier.svg|thumb|right|[[Podocyte]]s, cells which line the glomerulus, are negatively charged and have small gaps, preventing the filtration of large molecules. When damaged by [[inflammation]], this can result in an increased permeability to [[protein]]s]]
[[File:Filtration barrier.svg|thumb|right|[[Podocyte]]s, cells which line the glomerulus, are negatively charged and have small gaps, preventing the filtration of large molecules. When damaged by [[inflammation]], this can result in an increased permeability to [[protein]]s]]
{{Main|Nephritic syndrome}}
{{Main|Nephritic syndrome}}
The nephritic syndrome is characterised by [[haematuria|blood in the urine]] (especially [[Urinary cast|Red blood cell casts]] with dysmorphic red blood cells) and a [[oligouria|decrease in the amount of urine]] in the presence of [[hypertension]]. In this syndrome, inflammatory damage to cells lining the glomerulus are thought to result in destruction of the [[epithelium|epithelial]] barrier, leading to blood being found in the urine. At the same time, reactive changes, e.g. proliferation of mesangial cells,{{which|date=November 2013}} may result in a decrease in kidney blood flow, resulting in a decrease in the production of urine. The [[renin–angiotensin system]] may be subsequently activated, because of the decrease in perfusion of [[juxtaglomerular apparatus]], which may result in hypertension.<ref name=ROBBINS2007 />{{rp|554}}
The nephritic syndrome is characterised by [[haematuria|blood in the urine]] (especially [[Urinary cast|Red blood cell casts]] with dysmorphic red blood cells) and a [[oligouria|decrease in the amount of urine]] in the presence of [[hypertension]]. In this syndrome, inflammatory damage to cells lining the glomerulus are thought to result in destruction of the [[epithelium|epithelial]] barrier, leading to blood being found in the urine. At the same time, reactive changes, e.g. proliferation of mesangial cells,{{which|date=November 2013}} may result in a decrease in kidney blood flow, resulting in a decrease in the production of urine. The [[renin–angiotensin system]] may be subsequently activated, because of the decrease in perfusion of [[juxtaglomerular apparatus]], which may result in hypertension.<ref name="ROBBINS2007" />{{rp|554}}


==Nonproliferative==
==Nonproliferative==
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===Minimal change disease===
===Minimal change disease===
{{Main|Minimal change disease}}
{{Main|Minimal change disease}}
[[Minimal change disease]] is characterised as a cause of [[nephrotic syndrome]] without visible changes in the glomerulus on microscopy. Minimal change disease typically presents with [[edema]], an [[proteinuria|increase in proteins passed from urine]] and decrease in blood protein levels, and an increase in circulating [[lipid]]s (i.e., [[nephrotic syndrome]]) and is the most common cause of the nephrotic syndrome in children. Although no changes may be visible by light microscopy, changes on [[electron microscopy]] within the glomeruli may show a fusion of the foot processes of the [[podocyte]]s (cells lining the basement membrane of the capillaries of glomerulus). It is typically managed with [[corticosteroid]]s and does not progress to [[chronic kidney disease]].<ref name=DAVIDSONS2010 />{{rp|500}}<ref name=ROBBINS2007/>{{rp|550}}
[[Minimal change disease]] is characterised as a cause of [[nephrotic syndrome]] without visible changes in the glomerulus on microscopy. Minimal change disease typically presents with [[edema]], an [[proteinuria|increase in proteins passed from urine]] and decrease in blood protein levels, and an increase in circulating [[lipid]]s (i.e., [[nephrotic syndrome]]) and is the most common cause of the nephrotic syndrome in children. Although no changes may be visible by light microscopy, changes on [[electron microscopy]] within the glomeruli may show a fusion of the [[podocyte foot processes|foot processes]] of the [[podocyte]]s lining the basement membrane of the capillaries of glomerulus. It is typically managed with [[corticosteroid]]s and does not progress to [[chronic kidney disease]].<ref name="DAVIDSONS2010" />{{rp|500}}<ref name=ROBBINS2007/>{{rp|550}}


===Focal segmental glomerulosclerosis===
===Focal segmental glomerulosclerosis===
{{Main|Focal segmental glomerulosclerosis}}
{{Main|Focal segmental glomerulosclerosis}}


[[Focal segmental glomerulosclerosis]] is characterised by a [[fibrosis|sclerosis]] of segments of some glomeruli. It is likely to present as a nephrotic syndrome. This form of glomerulonephritis may be associated with conditions such as [[HIV]] and [[heroin]] abuse, or inherited as [[Alport syndrome]]. The cause of about 20–30% of focal-segmental glomerulosclerosis is unknown. On microscopy, affected glomeruli may show an increase in [[hyalin]], a pink and homogenous material, [[lipid|fat cells]], an increase in the mesangial matrix and collagen. Treatment may involve [[corticosteroid]]s, but up to half of people with focal segmental glomerulonephritis continue to have progressive deterioration of kidney function, ending in kidney failure.<ref name=ROBBINS2007 />{{rp|550–551}}
[[Focal segmental glomerulosclerosis]] is characterised by a [[fibrosis|sclerosis]] of segments of some glomeruli. It is likely to present as a nephrotic syndrome. This form of glomerulonephritis may be associated with conditions such as [[HIV]] and [[heroin]] abuse, or inherited as [[Alport syndrome]]. The cause of about 20–30% of focal-segmental glomerulosclerosis is unknown. On microscopy, affected glomeruli may show an increase in [[hyalin]], a pink and homogeneous material, [[lipid|fat cells]], an increase in the mesangial matrix and collagen. Treatment may involve [[corticosteroid]]s, but up to half of people with focal segmental glomerulonephritis continue to have progressive deterioration of kidney function, ending in kidney failure.<ref name="ROBBINS2007" />{{rp|550–551}}


===Membranous glomerulonephritis===
===Membranous glomerulonephritis===
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Microscopically, MGN is characterized by a thickened [[glomerular basement membrane]] without a hyperproliferation of the glomerular cells. [[Immunofluorescence]] demonstrates diffuse granular uptake of [[Immunoglobulin G|IgG]]. The basement membrane may completely surround the granular deposits, forming a "spike and dome" pattern. Tubules also display the symptoms of a typical Type III hypersensitivity reaction, which causes the endothelial cells to proliferate, which can be seen under a light microscope with a PAS stain.<ref>{{MedlinePlus|000472|Membranous nephropathy}}</ref>
Microscopically, MGN is characterized by a thickened [[glomerular basement membrane]] without a hyperproliferation of the glomerular cells. [[Immunofluorescence]] demonstrates diffuse granular uptake of [[Immunoglobulin G|IgG]]. The basement membrane may completely surround the granular deposits, forming a "spike and dome" pattern. Tubules also display the symptoms of a typical Type III hypersensitivity reaction, which causes the endothelial cells to proliferate, which can be seen under a light microscope with a PAS stain.<ref>{{MedlinePlus|000472|Membranous nephropathy}}</ref>


Prognosis follows the rule of thirds: one-third remain with MGN indefinitely, one-third remit, and one-third progress to [[end-stage kidney failure]]. As the glomerulonephritis progresses, the tubules of the kidney become infected, leading to atrophy and hyalinisation. The kidney appears to shrink. Treatment with [[corticosteroid]]s is attempted if the disease progresses.
Prognosis follows the rule of thirds: one-third remain with MGN indefinitely, one-third remit, and one-third progress to [[end-stage kidney failure]]. As the glomerulonephritis progresses, the tubules of the kidney become infected, leading to atrophy and hyalinisation. The kidney appears to shrink. Treatment with [[corticosteroid]]s is attempted if the disease progresses.{{cn|date=November 2023}}


In extremely rare cases, the disease has been known to run in families, usually passed down through the females. This condition, similarly, is called Familial Membranous Glomerulonephritis. There have only been about nine documented cases in the world.
In extremely rare cases, the disease has been known to run in families, usually passed down through the females. This condition, similarly, is called Familial Membranous Glomerulonephritis. There have only been about nine documented cases in the world.
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{{Main|IgA nephropathy}}
{{Main|IgA nephropathy}}


[[IgA nephropathy]], also known as ''Berger's disease'', is the most common type of glomerulonephritis, and generally presents with isolated visible or occult hematuria, occasionally combined with low grade proteinuria, and rarely causes a [[nephritic syndrome]] characterised by [[proteinuria]], and visible [[hematuria|blood in the urine]]. IgA nephropathy is classically described as a self-resolving form in young adults several days after a respiratory infection. It is characterised by deposits of [[IgA]] in the [[mesangium|space between glomerular capillaries]].<ref name=DAVIDSONS2010 />{{rp|501}}<ref name=ROBBINS2007 />{{rp|554–555}}
[[IgA nephropathy]], also known as ''Berger's disease'', is the most common type of glomerulonephritis, and generally presents with isolated visible or occult hematuria, occasionally combined with low grade proteinuria, and rarely causes a [[nephritic syndrome]] characterised by [[proteinuria]], and visible [[hematuria|blood in the urine]]. IgA nephropathy is classically described as a self-resolving form in young adults several days after a respiratory infection. It is characterised by deposits of [[IgA]] in the [[mesangium|space between glomerular capillaries]].<ref name="DAVIDSONS2010" />{{rp|501}}<ref name="ROBBINS2007" />{{rp|554–555}}


[[Henoch–Schönlein purpura]] refers to a form of IgA nephropathy, typically affecting children, characterised by a rash of [[petechiae|small bruises]] affecting the buttocks and lower legs, with abdominal pain.<ref name=DAVIDSONS2010 />{{rp|501}}
[[Henoch–Schönlein purpura]] refers to a form of IgA nephropathy, typically affecting children, characterised by a rash of [[petechiae|small bruises]] affecting the buttocks and lower legs, with abdominal pain.<ref name="DAVIDSONS2010" />{{rp|501}}


===Post-infectious===
===Post-infectious===
{{Main|Post-infectious glomerulonephritis}}
{{Main|Post-infectious glomerulonephritis}}


[[Post-infectious glomerulonephritis]] can occur after essentially any infection, but classically occurs after infection with the bacteria ''[[Streptococcus pyogenes]]''. It typically occurs 1–4 weeks after a [[pharynx|pharyngeal]] infection with this bacterium, and is likely to present with malaise, a slight [[fever]], [[nausea]] and a mild [[nephritic syndrome]] of moderately increased blood pressure, gross haematuria, and smoky-brown urine. Circulating [[immune complex]]es that deposit in the glomeruli may lead to an inflammatory reaction.<ref name=ROBBINS2007>{{cite book|editor-first=Vinay |editor-last=Kumar|title=Robbins basic pathology|year=2007|publisher=Saunders/Elsevier|location=Philadelphia|isbn=978-1-4160-2973-1|edition=8th}}</ref> {{rp|554–555}}
[[Post-infectious glomerulonephritis]] can occur after essentially any infection, but classically occurs after infection with the bacteria ''[[Streptococcus pyogenes]]''. It typically occurs 1–4 weeks after a [[pharynx|pharyngeal]] infection with this bacterium, and is likely to present with malaise, a slight [[fever]], [[nausea]] and a mild [[nephritic syndrome]] of moderately increased blood pressure, gross haematuria, and smoky-brown urine. Circulating [[immune complex]]es that deposit in the glomeruli may lead to an inflammatory reaction.<ref name="ROBBINS2007">{{Cite book |title=Robbins basic pathology |publisher=Saunders/Elsevier |year=2007 |isbn=978-1-4160-2973-1 |editor-last=Kumar |editor-first=Vinay |edition=8th}}</ref> {{rp|554–555}}


Diagnosis may be made on clinical findings or through [[antistreptolysin O]] antibodies found in the blood. A biopsy is seldom done, and the disease is likely to self-resolve in children in 1–4 weeks, with a poorer prognosis if adults are affected or if the affected children are obese.<ref name=DAVIDSONS2010>{{cite book|editor-first=Nicki R. |editor-last=Colledge |editor-first2=Brian R. |editor-last2=Walker |editor-first3=Stuart H. |editor-last3=Ralston |others=illust. Robert Britton|title=Davidson's principles and practice of medicine|year=2010|publisher=Churchill Livingstone/Elsevier|location=Edinburgh|isbn=978-0-7020-3084-0|edition=21st}}</ref> {{rp|501}} <ref>{{cite journal|vauthors=Lee MN, Shaikh U, Butani L|year=2009|title=Effect of overweight/obesity on recovery after post-infectious glomerulonephritis|journal=Clin Nephrol|volume=71|issue=6|pages=632–6|doi=10.5414/cnp71632|pmid=19473631}}</ref>
Diagnosis may be made on clinical findings or through [[antistreptolysin O]] antibodies found in the blood. A biopsy is seldom done, and the disease is likely to self-resolve in children in 1–4 weeks, with a poorer prognosis if adults are affected or if the affected children are obese.<ref name="DAVIDSONS2010">{{Cite book |title=Davidson's principles and practice of medicine |publisher=Churchill Livingstone/Elsevier |others=illust. Robert Britton |year=2010 |isbn=978-0-7020-3084-0 |editor-last=Colledge |editor-first=Nicki R. |edition=21st |editor-last2=Walker |editor-first2=Brian R. |editor-last3=Ralston |editor-first3=Stuart H.}}</ref> {{rp|501}} <ref>{{Cite journal |vauthors=Lee MN, Shaikh U, Butani L |year=2009 |title=Effect of overweight/obesity on recovery after post-infectious glomerulonephritis |journal=Clin Nephrol |volume=71 |issue=6 |pages=632–6 |doi=10.5414/cnp71632 |pmid=19473631}}</ref>


===Membranoproliferative===
===Membranoproliferative===
{{Main|Membranoproliferative glomerulonephritis}}
{{Main|Membranoproliferative glomerulonephritis}}
Membranoproliferative GN (MPGN), also known as ''mesangiocapillary glomerulonephritis,''<ref name=DAVIDSONS2010 />{{rp|502}} is characterised by an increase in the number of cells in the glomerulus, and alterations in the glomerular [[basement membrane]]. These forms present with the [[nephritic syndrome]], [[hypocomplementemia]], and have a poor prognosis. Three subtypes have been proposed:<ref name=ROBBINS2007 />{{rp|552–553}}
Membranoproliferative GN (MPGN), also known as ''mesangiocapillary glomerulonephritis,''<ref name="DAVIDSONS2010" />{{rp|502}} is characterised by an increase in the number of cells in the glomerulus, and alterations in the glomerular [[basement membrane]]. These forms present with the [[nephritic syndrome]], [[hypocomplementemia]], and have a poor prognosis. Three subtypes have been proposed:<ref name="ROBBINS2007" />{{rp|552–553}}
* Type 1 MPGN is caused by immune complex deposition in the mesangium and subendothelial space, typically secondary to [[systemic lupus erythematosus]], [[hepatitis B]] and [[hepatitis C|C]], or other chronic or recurring infections. Circulating immune complexes may activate the [[complement system]], leading to inflammation and an influx of inflammatory cells.<ref name=ROBBINS2007 />{{rp|552–553}}
* Type 1 MPGN is caused by immune complex deposition in the mesangium and subendothelial space, typically secondary to [[systemic lupus erythematosus]], [[hepatitis B]] and [[hepatitis C|C]], or other chronic or recurring infections. Circulating immune complexes may activate the [[complement system]], leading to inflammation and an influx of inflammatory cells.<ref name="ROBBINS2007" />{{rp|552–553}}
* Type 2 MPGN, also known as ''Dense Deposit Disease'', is characterised by an excessive activation of the complement system. The C3 Nephritic Factor [[autoantibody]] stabilizes [[C3-convertase]], which may lead to an excessive activation of complement.<ref name=ROBBINS2007 />{{rp|553}} Type 2 MPGN is a subgroup of C3 glomerulopathy, a newly proposed diagnosis which also encompasses C3 Glomerulonephritis (C3GN).<ref>{{Cite journal|last1=Tzoumas|first1=Nikolaos|last2=Hallam|first2=Dean|last3=Harris|first3=Claire L.|last4=Lako|first4=Majlinda|last5=Kavanagh|first5=David|last6=Steel|first6=David H.W.|date=November 2020|title=Revisiting the role of factor H in age-related macular degeneration: Insights from complement-mediated renal disease and rare genetic variants|url=https://doi.org/10.1016/j.survophthal.2020.10.008|journal=Survey of Ophthalmology|volume=66|issue=2|pages=378–401|doi=10.1016/j.survophthal.2020.10.008|pmid=33157112|s2cid=226274874|issn=0039-6257}}</ref><ref>{{Cite web|title=What is C3 Glomerulopathy?|url=https://www.atypicalhus.co.uk/c3g/what-is-c3-glomerulopathy/|access-date=2021-02-04|website=National Renal Complement Therapeutics Centre|language=en-GB}}</ref>
* Type 2 MPGN, also known as ''Dense Deposit Disease'', is characterised by an excessive activation of the complement system. The C3 Nephritic Factor [[autoantibody]] stabilizes [[C3-convertase]], which may lead to an excessive activation of complement.<ref name="ROBBINS2007" />{{rp|553}} Type 2 MPGN is a subgroup of C3 glomerulopathy, a newly proposed diagnosis which also encompasses C3 Glomerulonephritis (C3GN).<ref>{{Cite journal |last=Tzoumas |first=Nikolaos |last2=Hallam |first2=Dean |last3=Harris |first3=Claire L. |last4=Lako |first4=Majlinda |last5=Kavanagh |first5=David |last6=Steel |first6=David H.W. |date=November 2020 |title=Revisiting the role of factor H in age-related macular degeneration: Insights from complement-mediated renal disease and rare genetic variants |url=https://doi.org/10.1016/j.survophthal.2020.10.008 |journal=Survey of Ophthalmology |volume=66 |issue=2 |pages=378–401 |doi=10.1016/j.survophthal.2020.10.008 |pmid=33157112 |s2cid=226274874}}</ref><ref>{{Cite web |title=What is C3 Glomerulopathy? |url=https://www.atypicalhus.co.uk/c3g/what-is-c3-glomerulopathy/ |url-status=dead |archive-url=https://web.archive.org/web/20201020021746/https://www.atypicalhus.co.uk/c3g/what-is-c3-glomerulopathy/ |archive-date=2020-10-20 |access-date=2021-02-04 |website=National Renal Complement Therapeutics Centre |language=en-GB}}</ref>
* Type 3 MPGN, which is caused by immune complex deposition in the subepithelial space.
* Type 3 MPGN, which is caused by immune complex deposition in the subepithelial space.


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[[Image:Crescentic_glomerulonephritis_PAS_and_IF.png|thumb|[[Crescentic glomerulonephritis]] induced by infective [[endocarditis]] on [[Periodic acid-Schiff stain|PAS staining]] and [[immunofluorescence]]. PAS staining (left) demonstrated circumferential and cellular crescent formation with interstitial nephritis. Immunofluorescence (right) demonstrated [[Complement component 3|C3]] positive staining in [[Mesangium|mesangial area]].]]
[[Image:Crescentic_glomerulonephritis_PAS_and_IF.png|thumb|[[Crescentic glomerulonephritis]] induced by infective [[endocarditis]] on [[Periodic acid-Schiff stain|PAS staining]] and [[immunofluorescence]]. PAS staining (left) demonstrated circumferential and cellular crescent formation with interstitial nephritis. Immunofluorescence (right) demonstrated [[Complement component 3|C3]] positive staining in [[Mesangium|mesangial area]].]]
[[Image:Crescentic glomerulonephritis Periodic acid silver methanamine stain.JPEG|thumb|Photomicrograph of [[renal biopsy]] showing crescent formation and tuft narrowing. [[Periodic acid silver methenamine stain]].]]
[[Image:Crescentic glomerulonephritis Periodic acid silver methanamine stain.JPEG|thumb|Photomicrograph of [[renal biopsy]] showing crescent formation and tuft narrowing. [[Periodic acid silver methenamine stain]].]]
[[Rapidly progressive glomerulonephritis]], also known as ''crescentic GN'', is characterised by a rapid, progressive deterioration in kidney function. People with rapidly progressive glomerulonephritis may present with a [[nephritic syndrome]]. In management, [[steroid]] therapy is sometimes used, although the prognosis remains poor.<ref name=COUSER1999 /> Three main subtypes are recognised:<ref name=ROBBINS2007 />{{rp|557–558}}
[[Rapidly progressive glomerulonephritis]], also known as ''crescentic GN'', is characterised by a rapid, progressive deterioration in kidney function. People with rapidly progressive glomerulonephritis may present with a [[nephritic syndrome]]. In management, [[steroid]] therapy is sometimes used, although the prognosis remains poor.<ref name="COUSER1999" /> Three main subtypes are recognised:<ref name="ROBBINS2007" />{{rp|557–558}}
* Type 1 is [[Goodpasture syndrome]], an [[autoimmune disease]] also affecting the [[lung]]. In Goodpasture syndrome, [[Immunoglobulin G|IgG]] antibodies directed against the glomerular [[basement membrane]] trigger an inflammatory reaction, causing a [[nephritic syndrome]] and [[haemoptysis|the coughing up of blood]].<ref name=ROBBINS2007 />{{rp|557}} High dose immunosuppression is required (intravenous [[methylprednisolone]]) and cyclophosphamide, plus plasmapheresis. Immunohistochemistry staining of tissue specimens shows linear IgG deposits.
* Type 1 is [[Goodpasture syndrome]], an [[autoimmune disease]] also affecting the [[lung]]. In Goodpasture syndrome, [[Immunoglobulin G|IgG]] antibodies directed against the glomerular [[basement membrane]] trigger an inflammatory reaction, causing a [[nephritic syndrome]] and [[haemoptysis|the coughing up of blood]].<ref name="ROBBINS2007" />{{rp|557}} High dose immunosuppression is required (intravenous [[methylprednisolone]]) and cyclophosphamide, plus plasmapheresis. Immunohistochemistry staining of tissue specimens shows linear IgG deposits.
* Type 2 is characterised by immune-complex-mediated damage, and may be associated with [[systemic lupus erythematosus]], post-infective glomerulonephritis, IgA nephropathy, and [[Henoch–Schönlein purpura|IgA vasculitis]].<ref name=ROBBINS2007 />{{rp|558}}
* Type 2 is characterised by immune-complex-mediated damage, and may be associated with [[systemic lupus erythematosus]], post-infective glomerulonephritis, IgA nephropathy, and [[Henoch–Schönlein purpura|IgA vasculitis]].<ref name="ROBBINS2007" />{{rp|558}}
* Type 3 rapidly progressive glomerulonephritis, also called ''pauciimmune type'', is associated with causes of [[vasculitides|vascular inflammation]] including [[granulomatosis with polyangiitis]] (GPA) and [[microscopic polyangiitis]]. No immune deposits can be seen on staining, however blood tests may be positive for the [[Anti-neutrophil cytoplasmic antibody|ANCA]] antibody.<ref name=ROBBINS2007 />{{rp|558–559}}
* Type 3 rapidly progressive glomerulonephritis, also called ''pauciimmune type'', is associated with causes of [[vasculitides|vascular inflammation]] including [[granulomatosis with polyangiitis]] (GPA) and [[microscopic polyangiitis]]. No immune deposits can be seen on staining, however blood tests may be positive for the [[Anti-neutrophil cytoplasmic antibody|ANCA]] antibody.<ref name="ROBBINS2007" />{{rp|558–559}}


Histopathologically, the majority of glomeruli present "crescents". Formation of crescents is initiated by passage of fibrin into the Bowman space as a result of increased permeability of glomerular basement membrane. Fibrin stimulates the proliferation of endothelial cells of Bowman capsule, and an influx of monocytes. Rapid growing and fibrosis of crescents compresses the capillary loops and decreases the Bowman space, which leads to kidney failure within weeks or months. {{citation needed|date=November 2013}}
Histopathologically, the majority of glomeruli present "crescents". Formation of crescents is initiated by passage of fibrin into the Bowman space as a result of increased permeability of glomerular basement membrane. Fibrin stimulates the proliferation of endothelial cells of Bowman capsule, and an influx of monocytes. Rapid growing and fibrosis of crescents compresses the capillary loops and decreases the Bowman space, which leads to kidney failure within weeks or months. {{citation needed|date=November 2013}}


==Diagnosis==
==Diagnosis==
[[File:Ultrasonography of chronic renal disease caused by glomerulonephritis.jpg|thumb|[[Renal ultrasonography]] of chronic renal disease caused by glomerulonephritis with increased echogenicity and reduced cortical thickness. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.<ref name=Hansen2015>Content initially copied from: {{cite journal|last1=Hansen|first1=Kristoffer|last2=Nielsen|first2=Michael|last3=Ewertsen|first3=Caroline|title=Ultrasonography of the Kidney: A Pictorial Review|journal=Diagnostics|volume=6|issue=1|year=2015|pages=2|issn=2075-4418|doi=10.3390/diagnostics6010002|pmid=26838799|pmc=4808817|doi-access=free}} [https://creativecommons.org/licenses/by/4.0/ (CC-BY 4.0)]</ref>]]
[[File:Ultrasonography of chronic renal disease caused by glomerulonephritis.jpg|thumb|[[Renal ultrasonography]] of chronic renal disease caused by glomerulonephritis with increased echogenicity and reduced cortical thickness. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.<ref name="Hansen2015">Content initially copied from: {{Cite journal |last=Hansen |first=Kristoffer |last2=Nielsen |first2=Michael |last3=Ewertsen |first3=Caroline |year=2015 |title=Ultrasonography of the Kidney: A Pictorial Review |journal=Diagnostics |volume=6 |issue=1 |pages=2 |doi=10.3390/diagnostics6010002 |pmc=4808817 |pmid=26838799 |doi-access=free}}</ref>]]
Some forms of glomerulonephritis are diagnosed clinically, based on findings on history and examination. Other tests may include:<ref name=COUSER1999>{{cite journal|last=COUSER|first=W|title=Glomerulonephritis|journal=The Lancet|date=1 May 1999|volume=353|issue=9163|pages=1509–1515|doi=10.1016/S0140-6736(98)06195-9|pmid=10232333|s2cid=208793555}}</ref>
Some forms of glomerulonephritis are diagnosed clinically, based on findings on history and examination. Other tests may include:<ref name="COUSER1999">{{Cite journal |last=Couser |first=W. |date=May 1999 |title=Glomerulonephritis |journal=Lancet |volume=353 |issue=9163 |pages=1509–15 |doi=10.1016/S0140-6736(98)06195-9 |pmid=10232333 |s2cid=208793555}}</ref>
* Urine examination
* Urine examination
* Blood tests investigating the cause, including [[complete blood count|FBC]], [[inflammatory marker]]s, and special tests (including [[Anti-streptolysin O|ASLO]], [[Anti-neutrophil cytoplasmic antibody|ANCA]], [[Anti-GBM]], [[Complement system|Complement]] levels, [[Anti-nuclear antibody|Anti-nuclear antibodies]])
* Blood tests investigating the cause, including [[complete blood count|FBC]], [[inflammatory marker]]s, and special tests (including [[Anti-streptolysin O|ASLO]], [[Anti-neutrophil cytoplasmic antibody|ANCA]], [[Anti-GBM]], [[Complement system|Complement]] levels, [[Anti-nuclear antibody|Anti-nuclear antibodies]])

Latest revision as of 13:51, 22 September 2024

Not to be confused with glomerulonephrosis.
Glomerulonephritis
Other namesGlomerular nephritis
Photomicrograph of a kidney biopsy from a person with crescentic glomerulonephritis showing prominent fibrocellular crescent formation and moderate mesangial proliferation in a glomerulus. Hematoxylin and eosin stain.
SpecialtyNephrology

Glomerulonephritis (GN) is a term used to refer to several kidney diseases (usually affecting both kidneys). Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name,[1] but not all diseases necessarily have an inflammatory component.[citation needed]

As it is not strictly a single disease, its presentation depends on the specific disease entity: it may present with isolated hematuria and/or proteinuria (blood or protein in the urine); or as a nephrotic syndrome, a nephritic syndrome, acute kidney injury, or chronic kidney disease.

They are categorized into several different pathological patterns, which are broadly grouped into non-proliferative or proliferative types. Diagnosing the pattern of GN is important because the outcome and treatment differ in different types. Primary causes are intrinsic to the kidney. Secondary causes are associated with certain infections (bacterial, viral or parasitic pathogens), drugs, systemic disorders (SLE, vasculitis), or diabetes.

Signs and symptoms

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A glomerulus, a functional unit that represents the first step in the filtration of blood and generation of urine.

Glomerulonephritis refers to an inflammation of the glomerulus, which is the unit involved in filtration in the kidney. This inflammation typically results in one or both of the nephrotic or nephritic syndromes.[2]: 500 

Nephrotic syndrome

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Main article: Nephrotic syndrome

The nephrotic syndrome is characterised by the finding of edema in a person with increased protein in the urine and decreased protein in the blood, with increased fat in the blood. Inflammation that affects the cells surrounding the glomerulus, podocytes, increases the permeability to proteins, resulting in an increase in excreted proteins. When the amount of proteins excreted in the urine exceeds the liver's ability to compensate, fewer proteins are detected in the blood – in particular albumin, which makes up the majority of circulating proteins. With decreased proteins in the blood, there is a decrease in the oncotic pressure of the blood. This results in edema, as the oncotic pressure in tissue remains the same. Although decreased intravascular oncotic (i.e. osmotic) pressure partially explains the patient's edema, more recent studies have shown that extensive sodium retention in the distal nephron (collecting duct) is the predominant cause of water retention and edema in the nephrotic syndrome.[3] This is worsened by the secretion of the hormone aldosterone by the adrenal gland, which is secreted in response to the decrease in circulating blood and causes sodium and water retention. Hyperlipidemia is thought to be a result of the increased activity of the liver.[4]: 549 

Nephritic syndrome

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Podocytes, cells which line the glomerulus, are negatively charged and have small gaps, preventing the filtration of large molecules. When damaged by inflammation, this can result in an increased permeability to proteins
Main article: Nephritic syndrome

The nephritic syndrome is characterised by blood in the urine (especially Red blood cell casts with dysmorphic red blood cells) and a decrease in the amount of urine in the presence of hypertension. In this syndrome, inflammatory damage to cells lining the glomerulus are thought to result in destruction of the epithelial barrier, leading to blood being found in the urine. At the same time, reactive changes, e.g. proliferation of mesangial cells,[which?] may result in a decrease in kidney blood flow, resulting in a decrease in the production of urine. The renin–angiotensin system may be subsequently activated, because of the decrease in perfusion of juxtaglomerular apparatus, which may result in hypertension.[4]: 554 

Nonproliferative

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This is characterised by forms of glomerulonephritis in which the number of cells is not changed. These forms usually result in the nephrotic syndrome. Causes include:

Minimal change disease

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Main article: Minimal change disease

Minimal change disease is characterised as a cause of nephrotic syndrome without visible changes in the glomerulus on microscopy. Minimal change disease typically presents with edema, an increase in proteins passed from urine and decrease in blood protein levels, and an increase in circulating lipids (i.e., nephrotic syndrome) and is the most common cause of the nephrotic syndrome in children. Although no changes may be visible by light microscopy, changes on electron microscopy within the glomeruli may show a fusion of the foot processes of the podocytes lining the basement membrane of the capillaries of glomerulus. It is typically managed with corticosteroids and does not progress to chronic kidney disease.[2]: 500 [4]: 550 

Focal segmental glomerulosclerosis

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Main article: Focal segmental glomerulosclerosis

Focal segmental glomerulosclerosis is characterised by a sclerosis of segments of some glomeruli. It is likely to present as a nephrotic syndrome. This form of glomerulonephritis may be associated with conditions such as HIV and heroin abuse, or inherited as Alport syndrome. The cause of about 20–30% of focal-segmental glomerulosclerosis is unknown. On microscopy, affected glomeruli may show an increase in hyalin, a pink and homogeneous material, fat cells, an increase in the mesangial matrix and collagen. Treatment may involve corticosteroids, but up to half of people with focal segmental glomerulonephritis continue to have progressive deterioration of kidney function, ending in kidney failure.[4]: 550–551 

Membranous glomerulonephritis

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Main article: Membranous glomerulonephritis

Membranous glomerulonephritis may cause either nephrotic or a nephritic picture. About two-thirds are associated with auto-antibodies to phospholipase A2 receptor, but other associations include cancers of the lung and bowel, infections such as hepatitis B and malaria, drugs including penicillamine, and connective tissue diseases such as systemic lupus erythematosus. Individuals with cerebral shunts are at risk of developing shunt nephritis, which frequently produces MGN.[citation needed]

Microscopically, MGN is characterized by a thickened glomerular basement membrane without a hyperproliferation of the glomerular cells. Immunofluorescence demonstrates diffuse granular uptake of IgG. The basement membrane may completely surround the granular deposits, forming a "spike and dome" pattern. Tubules also display the symptoms of a typical Type III hypersensitivity reaction, which causes the endothelial cells to proliferate, which can be seen under a light microscope with a PAS stain.[5]

Prognosis follows the rule of thirds: one-third remain with MGN indefinitely, one-third remit, and one-third progress to end-stage kidney failure. As the glomerulonephritis progresses, the tubules of the kidney become infected, leading to atrophy and hyalinisation. The kidney appears to shrink. Treatment with corticosteroids is attempted if the disease progresses.[citation needed]

In extremely rare cases, the disease has been known to run in families, usually passed down through the females. This condition, similarly, is called Familial Membranous Glomerulonephritis. There have only been about nine documented cases in the world.

Thin basement membrane disease

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Main article: Thin basement membrane disease

Thin basement membrane disease is an autosomal dominant inherited disease characterized by thin glomerular basement membranes on electron microscopy. It is a benign condition that causes persistent microscopic hematuria. This also may cause proteinuria which is usually mild and overall prognosis is excellent. [citation needed]

Fibronectin glomerulopathy

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Fibronectin glomerulopathy is a rare form of glomerulopathy characterised by enlarged glomeruli with deposits in the mesangium and subendothelial space. The deposits have been shown to be fibronectin. This condition is inherited in an autosomal dominant fashion. About 40% of cases are due to mutations in the fibronectin (FN1) gene located on chromosome 2 (2q34).

Proliferative

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Proliferative glomerulonephritis is characterised by an increased number of cells in the glomerulus. These forms usually present with a triad of blood in the urine, decreased urine production, and hypertension, the nephritic syndrome. These forms usually progress to end-stage kidney failure (ESKF) over weeks to years (depending on type).

IgA nephropathy

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Main article: IgA nephropathy

IgA nephropathy, also known as Berger's disease, is the most common type of glomerulonephritis, and generally presents with isolated visible or occult hematuria, occasionally combined with low grade proteinuria, and rarely causes a nephritic syndrome characterised by proteinuria, and visible blood in the urine. IgA nephropathy is classically described as a self-resolving form in young adults several days after a respiratory infection. It is characterised by deposits of IgA in the space between glomerular capillaries.[2]: 501 [4]: 554–555 

Henoch–Schönlein purpura refers to a form of IgA nephropathy, typically affecting children, characterised by a rash of small bruises affecting the buttocks and lower legs, with abdominal pain.[2]: 501 

Post-infectious

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Main article: Post-infectious glomerulonephritis

Post-infectious glomerulonephritis can occur after essentially any infection, but classically occurs after infection with the bacteria Streptococcus pyogenes. It typically occurs 1–4 weeks after a pharyngeal infection with this bacterium, and is likely to present with malaise, a slight fever, nausea and a mild nephritic syndrome of moderately increased blood pressure, gross haematuria, and smoky-brown urine. Circulating immune complexes that deposit in the glomeruli may lead to an inflammatory reaction.[4] : 554–555 

Diagnosis may be made on clinical findings or through antistreptolysin O antibodies found in the blood. A biopsy is seldom done, and the disease is likely to self-resolve in children in 1–4 weeks, with a poorer prognosis if adults are affected or if the affected children are obese.[2] : 501  [6]

Membranoproliferative

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Main article: Membranoproliferative glomerulonephritis

Membranoproliferative GN (MPGN), also known as mesangiocapillary glomerulonephritis,[2]: 502  is characterised by an increase in the number of cells in the glomerulus, and alterations in the glomerular basement membrane. These forms present with the nephritic syndrome, hypocomplementemia, and have a poor prognosis. Three subtypes have been proposed:[4]: 552–553 

  • Type 1 MPGN is caused by immune complex deposition in the mesangium and subendothelial space, typically secondary to systemic lupus erythematosus, hepatitis B and C, or other chronic or recurring infections. Circulating immune complexes may activate the complement system, leading to inflammation and an influx of inflammatory cells.[4]: 552–553 
  • Type 2 MPGN, also known as Dense Deposit Disease, is characterised by an excessive activation of the complement system. The C3 Nephritic Factor autoantibody stabilizes C3-convertase, which may lead to an excessive activation of complement.[4]: 553  Type 2 MPGN is a subgroup of C3 glomerulopathy, a newly proposed diagnosis which also encompasses C3 Glomerulonephritis (C3GN).[7][8]
  • Type 3 MPGN, which is caused by immune complex deposition in the subepithelial space.

Rapidly progressive glomerulonephritis

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Main article: Rapidly progressive glomerulonephritis
Crescentic glomerulonephritis induced by infective endocarditis on PAS staining and immunofluorescence. PAS staining (left) demonstrated circumferential and cellular crescent formation with interstitial nephritis. Immunofluorescence (right) demonstrated C3 positive staining in mesangial area.
Photomicrograph of renal biopsy showing crescent formation and tuft narrowing. Periodic acid silver methenamine stain.

Rapidly progressive glomerulonephritis, also known as crescentic GN, is characterised by a rapid, progressive deterioration in kidney function. People with rapidly progressive glomerulonephritis may present with a nephritic syndrome. In management, steroid therapy is sometimes used, although the prognosis remains poor.[9] Three main subtypes are recognised:[4]: 557–558 

Histopathologically, the majority of glomeruli present "crescents". Formation of crescents is initiated by passage of fibrin into the Bowman space as a result of increased permeability of glomerular basement membrane. Fibrin stimulates the proliferation of endothelial cells of Bowman capsule, and an influx of monocytes. Rapid growing and fibrosis of crescents compresses the capillary loops and decreases the Bowman space, which leads to kidney failure within weeks or months. [citation needed]

Diagnosis

[edit]
Renal ultrasonography of chronic renal disease caused by glomerulonephritis with increased echogenicity and reduced cortical thickness. Measurement of kidney length on the US image is illustrated by '+' and a dashed line.[10]

Some forms of glomerulonephritis are diagnosed clinically, based on findings on history and examination. Other tests may include:[9]

Treatment

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Antibiotic therapy to prevent streptococcal infection (prophylaxis). Steroids to suppress inflammation. Provide high calories & low protein, sodium & potassium diet. Monitor for sign of kidney failure, heart failure, and hypertensive encephalopathy.

See also

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References

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  1. ^ "glomerulonephritis" at Dorland's Medical Dictionary
  2. ^ a b c d e f Colledge, Nicki R.; Walker, Brian R.; Ralston, Stuart H., eds. (2010). Davidson's principles and practice of medicine. illust. Robert Britton (21st ed.). Churchill Livingstone/Elsevier. ISBN 978-0-7020-3084-0.
  3. ^ Orth SR, Ritz E (April 1998). "The nephrotic syndrome". N Engl J Med. 338 (17): 1202–11. doi:10.1056/NEJM199804233381707. PMID 9554862.
  4. ^ a b c d e f g h i j k l m Kumar, Vinay, ed. (2007). Robbins basic pathology (8th ed.). Saunders/Elsevier. ISBN 978-1-4160-2973-1.
  5. ^ MedlinePlus Encyclopedia: Membranous nephropathy
  6. ^ Lee MN, Shaikh U, Butani L (2009). "Effect of overweight/obesity on recovery after post-infectious glomerulonephritis". Clin Nephrol. 71 (6): 632–6. doi:10.5414/cnp71632. PMID 19473631.
  7. ^ Tzoumas, Nikolaos; Hallam, Dean; Harris, Claire L.; Lako, Majlinda; Kavanagh, David; Steel, David H.W. (November 2020). "Revisiting the role of factor H in age-related macular degeneration: Insights from complement-mediated renal disease and rare genetic variants". Survey of Ophthalmology. 66 (2): 378–401. doi:10.1016/j.survophthal.2020.10.008. PMID 33157112. S2CID 226274874.
  8. ^ "What is C3 Glomerulopathy?". National Renal Complement Therapeutics Centre. Archived from the original on 2020-10-20. Retrieved 2021-02-04.
  9. ^ a b Couser, W. (May 1999). "Glomerulonephritis". Lancet. 353 (9163): 1509–15. doi:10.1016/S0140-6736(98)06195-9. PMID 10232333. S2CID 208793555.
  10. ^ a b Content initially copied from: Hansen, Kristoffer; Nielsen, Michael; Ewertsen, Caroline (2015). "Ultrasonography of the Kidney: A Pictorial Review". Diagnostics. 6 (1): 2. doi:10.3390/diagnostics6010002. PMC 4808817. PMID 26838799.
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