Renal amyloidosis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2] Omer Kamal, M.D. [2]
Synonyms and keywords:
Overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Omer Kamal, M.D. [2]
Overview
Nicolaus Fontanus was the first to describe amyloidosis based on the result of an autopsy while Rudolph Virchow was the first to introduce the term amyloidosis. Renal amyloidosis can be classified according to the site of amyloid deposition into glomerular, vascular, and tubular amyloidosis. Suggested mechanisms of renal involvement include abnormal protein production or hereditary mutation. If left untreated, renal amyloidosis may progress into end stage renal disease. Common complications include chronic renal failure and nephrotic syndrome. After a few years, renal amyloidosis eventually leads to end stage renal disease and it may be progressed in presence of certain factors such as steroid administration, renal vein thrombosis, infections and surgery. There is insufficient evidence to recommend routine screening for renal amyloidosis. Renal biopsy is the gold standard test for the diagnosis of renal diagnosis. The mainstay of treatment for renal amyloidosis is to decrease the production or increase clearing of amyloid. Pharmacologic medical therapies for renal amyloidosis include colchicine, azathioprine, dimethylsulfoxide, chlorambucil, methotrexate, cyclophosphamide and TNF-alpha antagonists (ie, etanercept, infliximab, and adalimumab).
Historical Perspective
Nicolaus Fontanus was the first to describe amyloidosis based on the result of an autopsy while Rudolph Virchow was the first to introduce the term amyloidosis.
Classification
Renal amyloidosis can be classified according to the site of amyloid deposition into glomerular, vascular, and tubular amyloidosis.
Pathophysiology
Suggested mechanisms of renal involvement include abnormal protein production or hereditary mutation.
Causes
Most common causes of renal amyloidosis include primary and secondary amyloidosis. Other causes include transthyretin and fibrinogen amyloid deposition.
Differentiating Renal amyloidosis from Other Diseases
Epidemiology and Demographics
The incidence is 97 to 140 cases per 100,000 individuals. The incidence of renal amyloidosis increases with age; the median age at diagnosis is 65 years.
Risk Factors
Common risk factors in the development of renal amyloidosis may be environmental and genetic such as heterozygous mutations in the genes for lysozyme, apolipoprotein AI, apolipoprotein AII, or fibrinogen A alpha-chain.
Screening
There is insufficient evidence to recommend routine screening for renal amyloidosis.
Natural History, Complications, and Prognosis
If left untreated, renal amyloidosis may progress into end stage renal disease. Common complications include chronic renal failure and nephrotic syndrome. After a few years, renal amyloidosis eventually leads to end stage renal disease and it may be accelerated by some factors such as steroid administration, renal vein thrombosis, infections and surgery.
Diagnosis
Diagnostic Study of Choice
Renal biopsy is the gold standard test for the diagnosis of renal diagnosis
History and Symptoms
The majority of patients with renal amyloidosis have proteinuria. Swelling is very common in lower limbs. Numbness or tingling in hands or feet (carpal tunnel syndrome) is a less common finding.
Physical Examination
Physical examination of patients with renal amyloidosis is usually remarkable for swelling, hepatosplenomegaly, facial or neck purpura and macroglossia. Fatigue and unintentional weight loss, are common in patients with AL amyloidosis. Tachycardia/bradycardia depends on the accompanying complication. Pulmonary fine crackles, faint pulmonary auscultation, suggestive of pleural effusion, decreased tactile fremitus and dull percussion.
Laboratory Findings
In patients with secondary amyloidosis, urinalysis should be routinely examined. Laboratory findings consistent with the diagnosis of renal amyloidosis include proteinuria and increased serum creatinine
Electrocardiogram
There are no ECG findings associated with renal amyloidosis.
X-ray
There are no definitive findings on x-ray associated with renal amyloidosis.
Echocardiography and Ultrasound
There are no echocardiography/ultrasound findings associated with renal amyloidosis
CT scan
There are no CT scan findings associated with renal amyloidosis
MRI
There are no MRI findings associated with renal amyloidosis.
Other Imaging Findings
There are no other imaging findings associated with renal amyloidosis
Other Diagnostic Studies
Kidney biopsy can represent amyloid deposition as vascular, tubulo-interstitial and/or glomerular deposits. All types of amyloidogenic proteins show affinity for Congo red dye.
Treatment
Medical Therapy
The mainstay of treatment for renal amyloidosis is to decrease the production or increase clearing of amyloid. Pharmacologic medical therapies for renal amyloidosis include colchicine, azathioprine, dimethylsulfoxide, chlorambucil, methotrexate, cyclophosphamide and TNF-alpha antagonists (ie, etanercept, infliximab, and adalimumab).
Surgery
In renal amyloidosis, surgery is usually reserved for patients developed with end stage renal disease. The patients with renal amyloidosis are good candidates for transplantation. In primary amyloidosis, renal transplantation is considered and it will improve long-term survival and quality of life.
Primary Prevention
There are no established measures for the primary prevention of renal amyloidosis.
Secondary Prevention
Treatment of the primary disease and underlying cause will provide favorable renal outcome. Template:WikiDoc Sources
Historical Perspective
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
Nicolaus Fontanus was the first to describe amyloidosis based on the result of an autopsy while Rudolph Virchow was the first to intoduce the term amyloidosis.
Historical Perspective
- In 1639, Nicolaus Fontanus autopsied a young man who had ascitis, jaundice, liver abscess and splenomegaly and his report has been the first description of amyloidosis.[1]
- In 1854, Rudolph Virchow introduced the term of amyloid as an macroscopic abnormality in some tissues.[2]
- In 1969, Finnish-type familial amyloidosis (FAF) was first described as one of the causes of renal amyloidosis.[3]
References
- ↑ Kyle RA (June 2011). “Amyloidosis: a brief history”. Amyloid. 18 Suppl 1: 6–7. doi:10.3109/13506129.2011.574354001. PMID 21838413.
- ↑ Sipe JD, Cohen AS (June 2000). “Review: history of the amyloid fibril”. J. Struct. Biol. 130 (2–3): 88–98. doi:10.1006/jsbi.2000.4221. PMID 10940217.
- ↑ Yamanaka S, Miyazaki Y, Kasai K, Ikeda S, Kiuru-Enari S, Hosoya T (April 2013). “Hereditary renal amyloidosis caused by a heterozygous G654A gelsolin mutation: a report of two cases”. Clin Kidney J. 6 (2): 189–93. doi:10.1093/ckj/sft007. PMC 4432447. PMID 26019848.
Classification
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
Renal amyloidosis can be classified according to the site of amyloid deposition into glomerular, vascular, and tubular amyloidosis.
Classification
Renal amyloidosis may be classified according to site of amyloid deposition into 3 subtypes:[1]
- Glomerular amyloid deposition (more common and have a poorer prognosis)
- Vascular amyloid deposition
- Tubular amyloid deposition
Renal amyloidosis may be classified according to type of amyloidogenic protein into 3 subtypes:[2]
| Amyloidosis type | Amyloidogenic protein | |
|---|---|---|
| Common types | AL/AHL/AH
(Primary amyloidosis) |
Ig light chains (AL) |
| Fragments of Ig heavy chains and light chains (AHL) | ||
| Fragments of heavy chains only (AH) | ||
| AA
(Secondary amyloidosis) |
Serum amyloid A | |
| Rare types | AFib | Fibrinogen A α chain |
| AApo AI/AII/AIV | Apo AI, Apo AII, or Apo AIV | |
| ATTR | Transthyretin | |
| ALys | Lysozyme | |
| AGel | Gelsolin | |
| ALECT2 | Leukocyte chemotactic factor 2 |
References
- ↑ Bilginer Y, Akpolat T, Ozen S (August 2011). “Renal amyloidosis in children”. Pediatr. Nephrol. 26 (8): 1215–27. doi:10.1007/s00467-011-1797-x. PMC 3119800. PMID 21360109.
- ↑ Said SM, Sethi S, Valeri AM, Leung N, Cornell LD, Fidler ME, Herrera Hernandez L, Vrana JA, Theis JD, Quint PS, Dogan A, Nasr SH (September 2013). “Renal amyloidosis: origin and clinicopathologic correlations of 474 recent cases”. Clin J Am Soc Nephrol. 8 (9): 1515–23. doi:10.2215/CJN.10491012. PMC 3805078. PMID 23704299.
Pathophysiology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
The kidney is the most involved organ in systemic amyloiosis. Suggested mechanisms of renal involvement include abnormal protein production or hereditary mutation.
Pathophysiology
Pathogenesis
- In systemic amyloidosis (AL/AH/AHL is much more common than AA) kidney is the most frequently involved organ.[1]
- In renal amyloidosis, the mechanisms of amyloidogenesis may include:[2]
- Abnormal protein production
- Overproduction wild-type proteins
- Decreased excretion of wild-type proteins
- Hereditary mutation
- In multiple myeloma, the cast nephropathy in distal tubules of nephrons results in renal impairment and deposition of AL amyloid protein in glomeruli can cause massive fibrillar involvement.[3]
Genetics
Hereditary amyloidosis due to amyloidogenic mutations:[4]
- Transthyretin (TTR) (most common inherited mutation)
- Fibrinogen
- Apolipoprotein A1
- Apolipoprotein A2
- Lysozyme
- Gelsolin genes
Associated Conditions
Gross Pathology
On gross pathology, amyloid looks “waxy” or “lardaceous” [7]
Microscopic Pathology
Microscopic Pathology of all types of amyloid after Congo red dye staining include: [2]
- Orange-red appearance by normal light microscopy
- Apple-green birefringence upon polarized light
For more general information about amyloidosis, click here.
References
- ↑ Said SM, Sethi S, Valeri AM, Leung N, Cornell LD, Fidler ME, Herrera Hernandez L, Vrana JA, Theis JD, Quint PS, Dogan A, Nasr SH (September 2013). “Renal amyloidosis: origin and clinicopathologic correlations of 474 recent cases”. Clin J Am Soc Nephrol. 8 (9): 1515–23. doi:10.2215/CJN.10491012. PMC 3805078. PMID 23704299.
- ↑ 2.0 2.1 Khalighi MA, Dean Wallace W, Palma-Diaz MF (April 2014). “Amyloid nephropathy”. Clin Kidney J. 7 (2): 97–106. doi:10.1093/ckj/sfu021. PMC 4377792. PMID 25852856.
- ↑ Hajra A, Bandyopadhyay D (2016). “An interesting case of renal amyloidosis”. Indian J Nephrol. 26 (6): 467–469. doi:10.4103/0971-4065.177143. PMC 5131391. PMID 27942184.
- ↑ Mahmood S, Palladini G, Sanchorawala V, Wechalekar A (February 2014). “Update on treatment of light chain amyloidosis”. Haematologica. 99 (2): 209–21. doi:10.3324/haematol.2013.087619. PMC 3912950. PMID 24497558.
- ↑ Ghiso J, Frangione B (December 2002). “Amyloidosis and Alzheimer’s disease”. Adv. Drug Deliv. Rev. 54 (12): 1539–51. PMID 12453671.
- ↑ Head E, Lott IT (April 2004). “Down syndrome and beta-amyloid deposition”. Curr. Opin. Neurol. 17 (2): 95–100. PMID 15021233.
- ↑ Kyle RA (September 2001). “Amyloidosis: a convoluted story”. Br. J. Haematol. 114 (3): 529–38. PMID 11552976.
Causes
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
The exact cause of renal amyloidiosis has not been identified. Most commonly causes of majority of the cases in renal amyloidosis idiopathic. Other causes include amyloidosis secondary to diseases such as tuberculosis, familial Mediterranean fever, rheumatoid arthritis, multiple myeloma or amyloidic mutations of transthyretin and fibrinogen protein.
Causes
Common Causes
In renal amyloidosis, most common causes include:[1]
- Idiopathic ( Primary (AL) amyloidosis )
- Amyloidosis secondary to:
Less Common Causes
In renal amyloidosis, less common causes include:[2]
- .Hereditary amyloidosis due to amyloidogenic mutations:
References
- ↑ Said SM, Sethi S, Valeri AM, Leung N, Cornell LD, Fidler ME, Herrera Hernandez L, Vrana JA, Theis JD, Quint PS, Dogan A, Nasr SH (September 2013). “Renal amyloidosis: origin and clinicopathologic correlations of 474 recent cases”. Clin J Am Soc Nephrol. 8 (9): 1515–23. doi:10.2215/CJN.10491012. PMC 3805078. PMID 23704299.
- ↑ Mahmood S, Palladini G, Sanchorawala V, Wechalekar A (February 2014). “Update on treatment of light chain amyloidosis”. Haematologica. 99 (2): 209–21. doi:10.3324/haematol.2013.087619. PMC 3912950. PMID 24497558.
Differentiating Renal amyloidosis from other Diseases
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
Differentiating [Disease name] from other Diseases
[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].
OR
[Disease name] must be differentiated from [differential dx1], [differential dx2], and [differential dx3].
OR
As [disease name] manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. [Subtype name 1] must be differentiated from other diseases that cause [clinical feature 1], such as [differential dx1] and [differential dx2]. In contrast, [subtype name 2] must be differentiated from other diseases that cause [clinical feature 2], such as [differential dx3] and [differential dx4].
Differentiating [disease name] from other diseases on the basis of [symptom 1], [symptom 2], and [symptom 3]
On the basis [symptom 1], [symptom 2], and [symptom 3], [disease name] must be differentiated from [disease 1], [disease 2], [disease 3], [disease 4], [disease 5], and [disease 6].
| Diseases | Clinical manifestations | Para-clinical findings | Gold standard | Additional findings | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Symptoms | Physical examination | ||||||||||||||
| Lab Findings | Imaging | Histopathology | |||||||||||||
| Symptom 1 | Symptom 2 | Symptom 3 | Physical exam 1 | Physical exam 2 | Physical exam 3 | Lab 1 | Lab 2 | Lab 3 | Imaging 1 | Imaging 2 | Imaging 3 | ||||
| Differential Diagnosis 1 | |||||||||||||||
| Differential Diagnosis 2 | |||||||||||||||
| Differential Diagnosis 3 | |||||||||||||||
| Diseases | Symptom 1 | Symptom 2 | Symptom 3 | Physical exam 1 | Physical exam 2 | Physical exam 3 | Lab 1 | Lab 2 | Lab 3 | Imaging 1 | Imaging 2 | Imaging 3 | Histopathology | Gold standard | Additional findings |
| Differential Diagnosis 4 | |||||||||||||||
| Differential Diagnosis 5 | |||||||||||||||
| Differential Diagnosis 6 | |||||||||||||||
References
Epidemiology and Demographics
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2] Omer Kamal, M.D. [2]
Overview
The incidence is 0.97 to 1.4 cases per 100,000 person-years. The prevalence of AL amyloidosis was 40.5 in 2015, an annual percentage change (APC) of 12%. In renal amyloidosis, is usually first diagnosed in average age of 65 years and it is uncommon before age of 40.
Epidemiology and Demographics
Incidence
The incidence is 0.97 to 1.4 cases per 100,000 person-years.[1]
Prevalence
The prevalence of AL amyloidosis was 40.5 in 2015, an annual percentage change (APC) of 12%. [1]
Mortality rate
- AL has higher mortality than AA type[2]
Age
- The incidence of renal amyloidosis increases with age; the median age at diagnosis is 65 years.[3][4]
Race
- There is no racial predilection to renal amyloidosis.
Gender
- Males are are more commonly affected by renal amyloidosis.
- The male to female ratio is approximately 2 to 1.[3]
Region
- ALECT2 is more frequent in the United States area.[5]
- AFib cases are most reported in Europe countries.
References
- ↑ 1.0 1.1 Quock TP, Yan T, Chang E, Guthrie S, Broder MS (May 2018). “Epidemiology of AL amyloidosis: a real-world study using US claims data”. Blood Adv. 2 (10): 1046–1053. doi:10.1182/bloodadvances.2018016402. PMC 5965052. PMID 29748430.
- ↑ Bollée G, Guery B, Joly D, Snanoudj R, Terrier B, Allouache M, Mercadal L, Peraldi MN, Viron B, Fumeron C, Elie C, Fakhouri F (March 2008). “Presentation and outcome of patients with systemic amyloidosis undergoing dialysis”. Clin J Am Soc Nephrol. 3 (2): 375–81. doi:10.2215/CJN.02470607. PMC 2390937. PMID 18184882.
- ↑ 3.0 3.1 Khalighi MA, Dean Wallace W, Palma-Diaz MF (April 2014). “Amyloid nephropathy”. Clin Kidney J. 7 (2): 97–106. doi:10.1093/ckj/sfu021. PMC 4377792. PMID 25852856.
- ↑ Hajra A, Bandyopadhyay D (2016). “An interesting case of renal amyloidosis”. Indian J Nephrol. 26 (6): 467–469. doi:10.4103/0971-4065.177143. PMC 5131391. PMID 27942184.
- ↑ Said SM, Sethi S, Valeri AM, Leung N, Cornell LD, Fidler ME, Herrera Hernandez L, Vrana JA, Theis JD, Quint PS, Dogan A, Nasr SH (September 2013). “Renal amyloidosis: origin and clinicopathologic correlations of 474 recent cases”. Clin J Am Soc Nephrol. 8 (9): 1515–23. doi:10.2215/CJN.10491012. PMC 3805078. PMID 23704299.
Risk Factors
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Omer Kamal, M.D. [2]
Overview
Common risk factors in the development of renal amyloidosis include genetic mutations such as heterozygous mutations in the genes for lysozyme, apolipoprotein AI, apolipoprotein AII, or fibrinogen A alpha-chain.
Risk Factors
The most potent risk factor in the development of renal amyloidosis are genetic mutations which include:[1][2]
- SAA1 gene mutaions
- Point mutations in the apoAI gene
- Point mutations in the apoAII gene
- Heterozygous mutations in the genes for lysozyme, apolipoprotein AI, apolipoprotein AII,, or fibrinogen A alpha-chain
References
- ↑ Obici L, Raimondi S, Lavatelli F, Bellotti V, Merlini G (October 2009). “Susceptibility to AA amyloidosis in rheumatic diseases: a critical overview”. Arthritis Rheum. 61 (10): 1435–40. doi:10.1002/art.24735. PMID 19790131.
- ↑ Booth DR, Booth SE, Gillmore JD, Hawkins PN, Pepys MB (December 1998). “SAA1 alleles as risk factors in reactive systemic AA amyloidosis”. Amyloid. 5 (4): 262–5. PMID 10036584.
Screening
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
There is insufficient evidence to recommend routine screening for renal amyloidosis.
Screening
There is insufficient evidence to recommend routine screening for renal amyloidosis.
References
Natural History, Complications and Prognosis
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shaghayegh Habibi, M.D.[2]
Overview
If left untreated, renal amyoidosis may progress into end stage renal disease. Common complications include chronic renal failure and nephrotic syndrome. After a few years, renal amyloidosis eventually leads to end stage renal disease and it may be accelerated by some factors such as steroid administration, renal vein thrombos, iInfections and surgery.
Natural History, Complications, and Prognosis
Natural History
If renal amyloidosis left untreated it usually manifests as nephrotic range proteinuria and then progresses to acute kidney injury and then end stage renal disease.[1]
Complications
Common complications of renal amyloidosis include:[2][3]
- ESRD
- Systemic organ involvement
Prognosis
After a few years, renal amyloidosis eventually leads to end stage renal disease. Disease progression is worsened in presence of certain factors such as:[4]
- Steroid administration
- Renal vein thrombosis
- Infections
- Surgery
References
- ↑ Lohani S, Schuiteman E, Garg L, Yadav D, Zarouk S (2016). “Apolipoprotein C-II Deposition Amyloidosis: A Potential Misdiagnosis as Light Chain Amyloidosis”. Case Rep Nephrol. 2016: 8690642. doi:10.1155/2016/8690642. PMC 5093243. PMID 27840752.
- ↑ Bilginer Y, Akpolat T, Ozen S (August 2011). “Renal amyloidosis in children”. Pediatr. Nephrol. 26 (8): 1215–27. doi:10.1007/s00467-011-1797-x. PMC 3119800. PMID 21360109.
- ↑ Hajra A, Bandyopadhyay D (2016). “An interesting case of renal amyloidosis”. Indian J Nephrol. 26 (6): 467–469. doi:10.4103/0971-4065.177143. PMC 5131391. PMID 27942184.
- ↑ Kaaroud H, Ben Moussa F, Goucha R, Abderrahim E, Ben Hamida F, Ben Hamida F, Ben Hamida F, Kheder A, Ben Miaz H (May 1999). “Influence of surgery on renal amyloidosis”. Kidney Int. 55 (5): 2117–2133. doi:10.1046/j.1523-1755.1999.00455.x. PMID 10231478.
Diagnosis
Diagnosis
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Treatment
Treatment
Medical Therapy | Surgery | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
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