Glomerular deposition disease: Difference between revisions
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The specific etiology that cause extra production of fibrills and chains in the | The specific etiology that cause extra production of fibrills and chains in the glomerular depositional diseases is unknown. | ||
==Differentiating from Other Diseases== | ==Differentiating from Other Diseases== | ||
Revision as of 15:18, 8 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], Aida Javanbakht, M.D.
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
Glomerular deposition diseases are classified in 5 types of diseases:
- Amyloidosis
- LCDD
- Fabry's disease
- Fibrillary immuno-tactoid glumerulopathy: The diagnosis is based on pathology finding. Infiltration of fibrills make glomerular structures in the kidney. Fibrills are larger than amyloid fibrils. Patients usually asymtomatic but, sometimes have proteinuria and hematuria. Prognosis is poor and ESRD will happen in half of the patients [2].
- Collagenofibrotic glomerulopathy: A rare disease and the diagnosis is based on pathology finding. Type III collagen fibers deposit in the subendothelial and mesangium in the kidney. Negetive with Congo red and thioflavin stains. There is no specific threatment for it[3] .
Pathophysiology
Pathogenesis:
The exact pathogenesis of LCDD 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 [4].
Accumulation of light chains→ tubular casts→ interstitial inflammation→ renal failure [5].
Microscopic Pathology
On light microscopy in LCDD:
- No glomerular and vascular abnormality
- Some tubular dilation with flattened epithelium→ suggest acute tubular injury
- negative Congo Red stain
On electron microscopy in LCDD:
- ground-pepper–like 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 that cause extra production of fibrills and chains in the glomerular depositional diseases is unknown.
Differentiating from Other Diseases
- Amyloidosis
- Diabetic Nephropathy
- IgA Nephropathy
- Fibrillary immuno-tactoid glumerulopathy
- Multiple Myeloma
- Fabry's disease
- Collagenofibrotic glomerulopathy
- Cryoglobulinemia
Epidemiology and Demographics
The incidence of LCDD is unknown. Most of the patients are men with the mean age of 58 years [1].
Renal involvement is the most common cause of mortality and morbidity in these patients. Survival varies between months to 10 years [6].
Risk Factors
There are no established risk factors for LCDD.
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 [7]
- Biopsy is the gold standard test
History and Symptoms
All organs can be effected by LCDD. Most of the time kidney is involved [8]. Usually patients are asymptomatic in early stages. Symptoms are nonspecific like fatigue and weight loss. 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, portal hypertension and 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 [9].
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)[10]
- Hematuria (usually microscopic)
- Abnormal liver enzyme ( in case of liver involvement)
Electrocardiogram
Arrhythmia like atrial fibrillation ( in case of heart involvement).
X-ray
There are no pathognomonic and specific x-ray findings associated with LCDD.
Echocardiography or Ultrasound
- Echocardiography:
In case of heart involvement: ↓ EF, diffuse hypokinesia, left ventricular concentric hypertrophy, ↓ diastolic compliance [11]
- Ultrasound:
No finding findings associated with renal LCDD.
CT scan
- In severe cases the size of the organ will ↑.
- No pathognomonic and specific finding associated with LCDD.
MRI
- In severe cases the size of the organ will ↑.
- No pathognomonic and specific finding associated with LCDD.
Other Imaging Findings
There are no other imaging findings associated with LCDD.
Other Diagnostic Studies
There are no other diagnostic studies associated with LCDD.
Treatment
Medical therapy:
70% of cases without therapy will have ESRD. There is no standard treatment for LCDD. Medical therapy options are:
- Symptomatic treatment for renal dysfunction like ACE inhibitors
- Chemotherapy with Bortezomib
- High-dose melphalan in conjunction with autologous stem cell transplantation
- If patient has LCDD and Multiple Myeloma (MM), should receive treatment per MM guideline
Surgery
In case of ESRD→ Kidney transplant
Primary Prevention
There are no established measures for the primary prevention of LCDD.
Secondary Prevention
There are no established measures for the secondary prevention of LCDD.
References
- ↑ 1.0 1.1 1.2 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.
- ↑ Alpers CE, Kowalewska J (January 2008). "Fibrillary glomerulonephritis and immunotactoid glomerulopathy". J. Am. Soc. Nephrol. 19 (1): 34–7. doi:10.1681/ASN.2007070757. PMID 18045849.
- ↑ Nimmagadda S, Mukku K, Devaraju SR, Uppin MS (2017). "Unusual cause of glomerular deposition disease: Collagenofibrotic glomerulopathy". Indian J Nephrol. 27 (1): 62–65. doi:10.4103/0971-4065.179300. PMC 5255993. PMID 28182050.
- ↑ 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.
- ↑ 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.
- ↑ Mohan M, Gokden M, Gokden N, Schinke C (March 2016). "A Case of Cardiac Light Chain Deposition Disease in a Patient with Solitary Plasmacytoma". Am J Case Rep. 17: 173–6. PMC 4801155. PMID 26988342.