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| {{SI}} | | {{Focal segmental glomerulosclerosis}} |
| {{CMG}}; '''Associate Editor-In-Chief:’’’ {{CZ}}
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| ==Overview==
| | '''For patient information on this page, click [[Focal segmental glomerulosclerosis (patient information)|here]]''' |
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| '''Focal segmental glomerulosclerosis''' (FSGS) is a cause of [[nephrotic syndrome]] in children and adolescents, as well as an important cause of [[kidney failure]] in adults.<ref name=Robbins_2005>{{cite book | author = Kumar V, Fausto N, Abbas A (editors) | title = Robbins & Cotran Pathologic Basis of Disease | edition = 7th | pages= pp. 982-3 | publisher = Saunders | year = 2003 | id = ISBN 978-0-721-60187-8 }}</ref> [[Minimal change disease]] (MCD) is by far the most common cause of nephrotic syndrome in children: MCD and primary FSGS may have a similar cause.<ref name=Robbins_2005 />
| | {{CMG}} {{APM}}; {{AE}}; {{MKA}}; {{MKK}}; {{OO}}; {{CZ}}; {{HK}}; {{SK}} FSGS |
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| The individual components of the name refer to the appearance of the kidney tissue on [[biopsy]]: ''focal'' - only some of the [[glomerulus|glomeruli]] are involved (as opposed to diffuse), ''segmental'' - only part of an entire glomerulus is involved (as opposed to global), ''glomerulosclerosis'' - refers to scarring of the [[glomerulus]] (a part of the [[nephron]] (the functional unit of the [[kidney]]))
| | == [[Focal segmental glomerulosclerosis overview|Overview]] == |
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| ==Symptoms & Signs== | | == [[Focal segmental glomerulosclerosis historical perspective|Historical Perspective]] == |
| In children and some adults, FSGS presents as a [[nephrotic syndrome]] (which is characterized by [[edema]] (associated with weight gain), [[hypoalbuminemia]] (low [[human serum albumin|serum albumin]] (a [[protein]]) in the blood), [[hyperlipidemia]] and [[hypertension]] (high blood pressure)). In adults it may also present as [[kidney failure]] and [[proteinuria]], without a full-blown [[nephrotic syndrome]].
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| == Classification == | | == [[Focal segmental glomerulosclerosis classification|Classification]] == |
| Depending on the cause it is broadly classified as
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| *Primary, when no underlying cause is found; usually presents as [[nephrotic syndrome]]
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| *Secondary, when an underlying cause is identified; usually presents with [[kidney failure]] and [[proteinuria]]. This is actually a heterogeneous group including a myriad causes such as
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| **Infections such as [[HIV]] (known as HIV-Associated Nephropathy)
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| **Toxins and drugs such as [[heroin]] and [[pamidronate]]
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| **Familial forms
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| **Secondary to [[nephron]] loss and hyperfiltration, such as with chronic [[pyelonephritis]] and [[reflux]], morbid [[obesity]], [[diabetes mellitus]]
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| There are many other classification schemes also.
| | == [[Focal segmental glomerulosclerosis pathophysiology|Pathophysiology]] == |
| ===Pathologic variants=== | |
| Five mutually exclusive variants of focal segmental glomerulosclerosis may be distinguished by the pathologic findings seen on renal biopsy:<ref name=thomas>Thomas DB, Franceschini N, Hogan SL, Ten Holder S, Jennette CE, Falk RJ, Jennette JC. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int. 2006 Mar;69(5):920-6. PMID 16518352</ref>
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| # Collapsing variant
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| # Glomerular tip lesion variant
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| # Cellular variant
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| # Perihilar variant
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| # Not otherwise specified (NOS) variant.
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| Recognition of these variants may have prognostic value in individuals with primary focal segmental glomerulosclerosis (i.e. where no underlying cause is identified). The collapsing variant is associated with higher rate of progression to end-stage renal disease, whereas glomerular tip lesion variant has low rate of progression to end-stage renal disease in most patients.<ref name=thomas/> Cellular variant shows similar clinical presentation to collapsing and glomerular tip variant but has intermediate outcomes between these two variants. However, because collapsing and glomerular tip variant show overlapping pathologic features with cellular variant, this intermediate difference in clinical outcomes may reflect sampling bias in cases of cellular focal segmental glomerulosclerosis (i.e. unsampled collapsing variant or glomerular tip variant). The prognostic significance of perihilar and NOS variants has not yet been determined. The NOS variant is the most common subtype.<ref name=thomas/>
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| ==Causes== | | == [[Focal segmental glomerulosclerosis causes|Causes]] == |
| There are currently three known genetic causes of the hereditary forms of FSGS.
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| * The first gene involved with this disorder is ACTN4, which encodes alpha-actinin 4. This protein crosslinks bundles of actin filaments and is present in the [[podocyte]]. Mutations in this protein associated with FSGS result in increased affinity for actin binding, formation of intracellular aggregates, and decreased protein half-life. While it is unclear how these effects might lead to FSGS there are a number of theories. Firstly, protein aggregation may have a toxic affect on the podocyte. Secondly, decreased protein half-life or increased affinity for actin binding may alter actin polymerization and thereby affect the podocytes cytoskeletal architecture.<ref name=Mukerji_2007>{{cite journal |author=Mukerji N, Damodaran TV, Winn MP |title=TRPC6 and FSGS: The latest TRP channelopathy |journal= |volume= |issue= |pages= |year=2007 |pmid=17459670}}</ref>
| | == [[Focal segmental glomerulosclerosis differential diagnosis|Differentiating Focal segmental glomerulosclerosis from other Diseases]] == |
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| * A second gene associated with FSGS is [[TRPC6]], which encodes a member of the canonical family of [[Transient receptor potential|TRP channel]]s. This family of ion channels conduct cations in a largely non-selective manner. As with ACTN4, TRPC6 is expressed in [[podocyte]]s. While TRP channels can be activated through a variety of methods, TRPC6 is known to be activated by [[phospholipase C]] stimulation. There are at least 6 mutations in this channel, located throughout the channel. At least one of these mutations, P112Q, leads to increased intracellular calcium influx. It is unclear how this might lead to FSGS, though it has been proposed that it may result in alteration of podocyte dynamics or podocytopenia.<ref name=Mukerji_2007/>
| | == [[Focal segmental glomerulosclerosis epidemiology and demographics|Epidemiology and Demographics]] == |
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| * The final gene known to be involved in hereditary forms of FSGS is the p130(Cas) ligand. The mouse homologue of this protein, CD2, is located in podocytes where it interacts with [[fyn (biochemistry)|fyn]] and synaptopodin. Mutations in this gene associated with FSGS occur at [[Splicing (genetics)|splice sites]] and lead to altered protein translation. This has been theorized to result in altered actin binding and, thus, alteration of the cytoskeletal podocyte architecture.<ref name=Mukerji_2007/>
| | == [[Focal segmental glomerulosclerosis risk factors|Risk Factors]] == |
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| ==Diagnosis== | | == [[Focal segmental glomerulosclerosis natural history, complications and prognosis|Natural History, Complications and Prognosis]] == |
| *[[urinalysis]]
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| *[[blood tests]] - cholesterol
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| *kidney [[Needle aspiration biopsy|biopsy]]
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| ==Differential Diagnosis== | | == Diagnosis == |
| *[[Minimal change disease]], especially in children
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| *several others
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| ==Treatment==
| | [[Focal segmental glomerulosclerosis history and symptoms|History and Symptoms]] | [[Focal segmental glomerulosclerosis physical examination|Physical Examination]] | [[Focal segmental glomerulosclerosis laboratory findings|Laboratory Findings]] | [[Focal segmental glomerulosclerosis chest x ray|Chest X Ray]] | [[Focal segmental glomerulosclerosis CT|CT]] | [[Focal segmental glomerulosclerosis MRI|MRI]] | [[Focal segmental glomerulosclerosis ultrasound|Ultrasound]] | [[Focal segmental glomerulosclerosis other imaging findings|Other Imaging Findings]] | [[Focal segmental glomerulosclerosis other diagnostic studies|Other Diagnostic Studies]] |
| * Salt restriction and [[diuretics]] (water pills), such as [[furosemide]], for edema
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| * Antihypertensives (especially [[ACE inhibitors|ACEI]]s) - if the blood pressure is too high
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| * treat present [[hyperlipidemia]] (e.g. [[statin]]s, [[fibrate]]s)
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| * [[Corticosteroid]]s, such as [[prednisone]] - based on the clinical judgment of [[physician]] (no broad consensus/guideline)
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| * [[Cytotoxic]]s, such as [[cyclophosphamide]] may be used to induce remission in patients presenting with FSGS refractory to corticosteroids, or in patients who do not tolerate steroids.
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| * [[Plasmapheresis]] - blood cleansing using a machine to remove the patient's [[blood plasma]] and replacing it with donor plasma.
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| *None - sometimes none of the above works and the patient will required [[dialysis]] with possibly later [[transplantation]] of a new kidney.
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| ==References== | | == Treatment == |
| {{Reflist|2}}
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| | [[Focal segmental glomerulosclerosis medical therapy|Medical Therapy]] | [[Focal segmental glomerulosclerosis surgery|Surgery]] | [[Focal segmental glomerulosclerosis primary prevention|Primary Prevention]] | [[Focal segmental glomerulosclerosis secondary prevention|Secondary Prevention]] | [[Focal segmental glomerulosclerosis cost-effectiveness of therapy| Cost-Effectiveness of Therapy]] | [[Focal segmental glomerulosclerosis future or investigational therapies|Future or Investigational Therapies]] |
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| | ==Case Studies== |
| | [[Focal segmental glomerulosclerosis case study one|Case #1]] |
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| {{Nephrology}} | | {{Nephrology}} |
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| [[Category:Disease]] | | [[Category:Nephrology]] |
| [[Category:Kidney diseases]]
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| [[Category: Channelopathy]]
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| [[ja:巣状糸球体硬化症]] | | [[ja:巣状糸球体硬化症]] |
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| {{WH}} | | {{WH}} |
| {{WS}} | | {{WS}} |
| | [[Category:Up-To-Date]] |
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| | [[Category:Medicine]] |
| | [[Category:Nephrology]] |