Glomerular deposition disease: Difference between revisions
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The exact pathogenesis of light chain deposition disease is not fully understood. Accumulation of monoclonal [[light chains]] and [[matrix protein]]<nowiki/>s → ↑ quantity and activity of transforming growth factor-beta ([[TGF-beta]]). | The exact pathogenesis of light chain deposition disease is not fully understood. Accumulation of monoclonal [[light chains]] and [[matrix protein]]<nowiki/>s → ↑ quantity and activity of transforming growth factor-beta ([[TGF-beta]]). | ||
* TGF-beta → inhibit [[mesangial cell]] proliferation and ↑ [[matrix protein]] production | * TGF-beta → inhibit [[mesangial cell]] proliferation and ↑ [[matrix protein]] production | ||
* ↑ [[matrix protein]]<nowiki/>s accumulation → compress the [[Glomerular capillaries|glomerular]] capillaryies → [[renal failure]] <ref name="pmid7639331">{{cite journal |vauthors=Zhu L, Herrera GA, Murphy-Ullrich JE, Huang ZQ, Sanders PW |title=Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-beta |journal=Am. J. Pathol. |volume=147 |issue=2 |pages=375–85 |date=August 1995 |pmid=7639331 |pmc=1869812 |doi= |url=}}</ref>. | |||
* ↑ [[matrix protein]]<nowiki/>s accumulation → compress the [[Glomerular capillaries|glomerular]] capillaryies → [[renal failure]] <ref name="pmid7639331">{{cite journal |vauthors=Zhu L, Herrera GA, Murphy-Ullrich JE, Huang ZQ, Sanders PW |title=Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-beta |journal=Am. J. Pathol. |volume=147 |issue=2 |pages=375–85 |date=August 1995 |pmid=7639331 |pmc=1869812 |doi= |url=}}</ref>. | |||
Accumulation of [[light chain]]<nowiki/>s→ [[tubular]] casts→ interstitial [[inflammation]]→ [[renal failure]] <ref name="pmid10919389">{{cite journal |vauthors=Herrera GA |title=Renal manifestations of plasma cell dyscrasias: an appraisal from the patients' bedside to the research laboratory |journal=Ann Diagn Pathol |volume=4 |issue=3 |pages=174–200 |date=June 2000 |pmid=10919389 |doi= |url=}}</ref>. | |||
== Microscopic Pathology == | |||
On [[Light microscope|light microscop]]<nowiki/>y: | |||
* No [[glomerular]] and [[vascular]] abnormality | |||
* Some [[tubular]] dilation with flattened [[epithelium]]→ suggest [[Acute tubular insufficiency|acute tubular]] injury | |||
On [[Electron-micrograph|electron]] microscopy: | |||
* electron-dense deposits in the [[Mesangial cells|mesangia]]<nowiki/>l and the [[endothelial]] of the [[glomerular basement membrane]]. Also, in [[renal tubule]]<nowiki/>s if there is [[Tubular|tubular involvement]]. | |||
== Genetics == | == Genetics == | ||
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The incidence of LCDD is unknown. Most of the patients are men with the mean age of 58 years <ref name="pmid146551862">{{cite journal |vauthors=Pozzi C, D'Amico M, Fogazzi GB, Curioni S, Ferrario F, Pasquali S, Quattrocchio G, Rollino C, Segagni S, Locatelli F |title=Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors |journal=Am. J. Kidney Dis. |volume=42 |issue=6 |pages=1154–63 |date=December 2003 |pmid=14655186 |doi= |url=}}</ref>. | The incidence of LCDD is unknown. Most of the patients are men with the mean age of 58 years <ref name="pmid146551862">{{cite journal |vauthors=Pozzi C, D'Amico M, Fogazzi GB, Curioni S, Ferrario F, Pasquali S, Quattrocchio G, Rollino C, Segagni S, Locatelli F |title=Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors |journal=Am. J. Kidney Dis. |volume=42 |issue=6 |pages=1154–63 |date=December 2003 |pmid=14655186 |doi= |url=}}</ref>. | ||
Renal involvement is the most common cause of mortality and morbidity in these patients. | Renal involvement is the most common cause of mortality and morbidity in these patients. Survival varies between months to 10 years <ref name="pmid11423577">{{cite journal |vauthors=Lin J, Markowitz GS, Valeri AM, Kambham N, Sherman WH, Appel GB, D'Agati VD |title=Renal monoclonal immunoglobulin deposition disease: the disease spectrum |journal=J. Am. Soc. Nephrol. |volume=12 |issue=7 |pages=1482–92 |date=July 2001 |pmid=11423577 |doi= |url=}}</ref>. | ||
==Risk Factors== | ==Risk Factors== | ||
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==Screening== | ==Screening== | ||
There is insufficient evidence to recommend routine screening for | There is insufficient evidence to recommend routine screening for LCDD. | ||
==Natural History, Complications, and Prognosis== | ==Natural History, Complications, and Prognosis== | ||
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==Diagnosis== | ==Diagnosis== | ||
===Diagnostic Study of Choice=== | ===Diagnostic Study of Choice=== | ||
* Complete blood test | * Complete [[Blood tests|blood test]] | ||
* Urine and serum electrophoresis | * Urine and serum [[electrophoresis]] | ||
* | * Serum and urine immunoglobulin free [[light chain]] assays <ref name="pmid25296094">{{cite journal |vauthors=Yadav P, Leung N, Sanders PW, Cockwell P |title=The use of immunoglobulin light chain assays in the diagnosis of paraprotein-related kidney disease |journal=Kidney Int. |volume=87 |issue=4 |pages=692–7 |date=April 2015 |pmid=25296094 |pmc=4863638 |doi=10.1038/ki.2014.333 |url=}}</ref> | ||
* [[Biopsy]] | |||
===History and Symptoms=== | ===History and Symptoms=== | ||
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* [[Proteinuria]] (30-50% of cases have [[nephrotic syndrome]])<ref name="pmid2106817">{{cite journal |vauthors=Buxbaum JN, Chuba JV, Hellman GC, Solomon A, Gallo GR |title=Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis |journal=Ann. Intern. Med. |volume=112 |issue=6 |pages=455–64 |date=March 1990 |pmid=2106817 |doi= |url=}}</ref> | * [[Proteinuria]] (30-50% of cases have [[nephrotic syndrome]])<ref name="pmid2106817">{{cite journal |vauthors=Buxbaum JN, Chuba JV, Hellman GC, Solomon A, Gallo GR |title=Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis |journal=Ann. Intern. Med. |volume=112 |issue=6 |pages=455–64 |date=March 1990 |pmid=2106817 |doi= |url=}}</ref> | ||
* [[Hematuria]] (usually microscopic) | * [[Hematuria]] (usually microscopic) | ||
===Electrocardiogram=== | ===Electrocardiogram=== | ||
[[Arrhythmia]] like [[atrial fibrillation]] ( in heart involving type). | |||
===X-ray=== | ===X-ray=== | ||
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==Treatment== | ==Treatment== | ||
'''Medical therapy:''' | |||
70% of cases without therapy will have [[ESRD]]. There is no standard treatment for LCDD. Medical therapy options are: | |||
* [[Chemotherapy]] with [[Bortezomib]] | |||
[ | |||
* High-dose [[melphalan]] in conjunction with [[autologous]] [[stem cell transplantation]] | |||
===Surgery=== | ===Surgery=== | ||
Revision as of 22:55, 6 June 2018
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]
Synonyms and keywords: light chain deposition disease
Overview
Light chain deposition disease (LCDD) is a rare blood cell disease which is characterized by deposition of fragments of infection-fighting immunoglobulins, called light chains, in the body. These light chain deposits damage organs and cause disease. The kidneys are almost always affected and this often leads to Chronic renal failure. About half of people with light chain deposition disease also have multiple myeloma. Unlike in AL Amyloidosis, in which light chains are laid down in characteristic amyloid deposits, in LCDD, light chains are deposited in non-amyloid granules. Light chains in LCDD are kappa light chains in granular shape[1].
Classification
There is no established system for the classification of LCDD.
Pathophysiology
Pathogenesis:
The exact pathogenesis of light chain deposition disease is not fully understood. Accumulation of monoclonal light chains and matrix proteins → ↑ quantity and activity of transforming growth factor-beta (TGF-beta).
- TGF-beta → inhibit mesangial cell proliferation and ↑ matrix protein production
- ↑ matrix proteins accumulation → compress the glomerular capillaryies → renal failure [2].
Accumulation of light chains→ tubular casts→ interstitial inflammation→ renal failure [3].
Microscopic Pathology
On light microscopy:
- No glomerular and vascular abnormality
- Some tubular dilation with flattened epithelium→ suggest acute tubular injury
On electron microscopy:
- electron-dense deposits in the mesangial and the endothelial of the glomerular basement membrane. Also, in renal tubules if there is tubular involvement.
Genetics
There exact genetic association for LCDD is unknown.
Causes
The specific etiology is unknown.
Differentiating from Other Diseases
- Amyloidosis
- Diabetic Nephropathy
- IgA Nephropathy
- Multiple Myeloma
- Cryoglobulinemia
Epidemiology and Demographics
The incidence of LCDD is unknown. Most of the patients are men with the mean age of 58 years [4].
Renal involvement is the most common cause of mortality and morbidity in these patients. Survival varies between months to 10 years [5].
Risk Factors
There are no established risk factors for [disease name].
OR
The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
OR
Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
Screening
There is insufficient evidence to recommend routine screening for LCDD.
Natural History, Complications, and Prognosis
Prognostic factors at presentation [1]:
- Age
- underlying hematologic disease
- Light chain deposition in other organs
- Renal function
- other medical diseases like diabetic nephropathy
The median time to progression to chronic renal failure is 2.7 years. After 5 years, about 37% of patients with LCDD are alive and do not have end stage renal disease.
Diagnosis
Diagnostic Study of Choice
- Complete blood test
- Urine and serum electrophoresis
- Serum and urine immunoglobulin free light chain assays [6]
- Biopsy
History and Symptoms
All organs can be effected by LCDD. Most of the time kidney is involved [7]. Usually patients are asymptomatic in early stages. Rapidly progressive glomerulonephritis or acute tubulointerstitial nephritis cause renal failure in these patients. Other than the kidneys, liver and heart are the most commonly involved organs. Deposition of light chains in the liver may lead to hepatomegaly, an enlarged liver, or rarely portal hypertension or liver failure. The heart is affected in up to 80% of patients with LCDD, and may cause arrhythmias restrictive cardiomyopathy, cardiomegaly, and congestive heart failure [8].
Physical Examination
- Depends on involvement of the organ you may find organomegaly like hepatomegaly
- Polyneuropathy
Laboratory Findings
- Proteinuria (30-50% of cases have nephrotic syndrome)[9]
- Hematuria (usually microscopic)
Electrocardiogram
Arrhythmia like atrial fibrillation ( in heart involving type).
X-ray
There are no x-ray findings associated with [disease name].
OR
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with [disease name].
OR
Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
CT scan
There are no CT scan findings associated with [disease name].
OR
[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
MRI
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Other Imaging Findings
There are no other imaging findings associated with [disease name].
OR
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
Other Diagnostic Studies
There are no other diagnostic studies associated with [disease name].
OR
[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR
Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
Treatment
Medical therapy:
70% of cases without therapy will have ESRD. There is no standard treatment for LCDD. Medical therapy options are:
- Chemotherapy with Bortezomib
- High-dose melphalan in conjunction with autologous stem cell transplantation
Surgery
Surgical intervention is not recommended for the management of [disease name].
OR
Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
OR
The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
OR
The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
OR
Surgery is the mainstay of treatment for [disease or malignancy].
Primary Prevention
There are no established measures for the primary prevention of [disease name].
OR
There are no available vaccines against [disease name].
OR
Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
OR
[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].
Secondary Prevention
There are no established measures for the secondary prevention of [disease name].
OR
Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
References
- ↑ 1.0 1.1 Pozzi C, D'Amico M, Fogazzi GB, Curioni S, Ferrario F, Pasquali S, Quattrocchio G, Rollino C, Segagni S, Locatelli F (December 2003). "Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors". Am. J. Kidney Dis. 42 (6): 1154–63. PMID 14655186.
- ↑ Zhu L, Herrera GA, Murphy-Ullrich JE, Huang ZQ, Sanders PW (August 1995). "Pathogenesis of glomerulosclerosis in light chain deposition disease. Role for transforming growth factor-beta". Am. J. Pathol. 147 (2): 375–85. PMC 1869812. PMID 7639331.
- ↑ Herrera GA (June 2000). "Renal manifestations of plasma cell dyscrasias: an appraisal from the patients' bedside to the research laboratory". Ann Diagn Pathol. 4 (3): 174–200. PMID 10919389.
- ↑ Pozzi C, D'Amico M, Fogazzi GB, Curioni S, Ferrario F, Pasquali S, Quattrocchio G, Rollino C, Segagni S, Locatelli F (December 2003). "Light chain deposition disease with renal involvement: clinical characteristics and prognostic factors". Am. J. Kidney Dis. 42 (6): 1154–63. PMID 14655186.
- ↑ Lin J, Markowitz GS, Valeri AM, Kambham N, Sherman WH, Appel GB, D'Agati VD (July 2001). "Renal monoclonal immunoglobulin deposition disease: the disease spectrum". J. Am. Soc. Nephrol. 12 (7): 1482–92. PMID 11423577.
- ↑ Yadav P, Leung N, Sanders PW, Cockwell P (April 2015). "The use of immunoglobulin light chain assays in the diagnosis of paraprotein-related kidney disease". Kidney Int. 87 (4): 692–7. doi:10.1038/ki.2014.333. PMC 4863638. PMID 25296094.
- ↑ Ronco PM, Alyanakian MA, Mougenot B, Aucouturier P (July 2001). "Light chain deposition disease: a model of glomerulosclerosis defined at the molecular level". J. Am. Soc. Nephrol. 12 (7): 1558–65. PMID 11423587.
- ↑ Koopman P, Van Dorpe J, Maes B, Dujardin K (December 2009). "Light chain deposition disease as a rare cause of restrictive cardiomyopathy". Acta Cardiol. 64 (6): 821–4. doi:10.2143/AC.64.6.2044752. PMID 20128164.
- ↑ Buxbaum JN, Chuba JV, Hellman GC, Solomon A, Gallo GR (March 1990). "Monoclonal immunoglobulin deposition disease: light chain and light and heavy chain deposition diseases and their relation to light chain amyloidosis. Clinical features, immunopathology, and molecular analysis". Ann. Intern. Med. 112 (6): 455–64. PMID 2106817.