Glomerular deposition disease
Synonyms and keywords: light chain deposition disease, LCDD

# Overview
Localized deposition of fibrils and proteins in glumerole is called glomerular deposition disease.
Light chain deposition disease (LCDD) is one of the glomerular deposition disease. It's 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.

# Classification
Glomerular deposition disease may be classified according to pathology findings into into 5 groups: 
- LCDD
- Amyloidosis
- Fabry's disease
- Fibrillary immuno-tactoid glumerulopathy
- Collagenofibrotic glomerulopathy

# Pathophysiology

## Pathogenesis:
Deposits of abnormal or extra production of proteins, lipids and fibrills in the glomeruls cause glomerular deposition diseases.
-In LCDD:
light chains are small polypeptides produced by B lymphocytes.They are sub units of antibodies. Kappa and Lambda are two types of light chains. Excess production of Kappa chain and accumulation in the renal glumerulus cause LCDD. The exact mechanism of increase production of light chains and reason that renal attracts them is unknown. These chains can deposit in all parts of renal glumeruls and tubuls.
Accumulation of monoclonal light chains and matrix proteins cause increase quantity and activity of transforming growth factor-beta (TGF-beta). TGF-beta inhibits mesangial cell proliferation and increase matrix protein production
- Accumulation of matrix proteins  compress the glomerular capillaryies and cause renal failure.
Besides glumerulus,light chains may accumulate in renal tubular and make tubular casts. These casts cause interstitial inflammation and renal failure.
- In Amyloidosis:
Amyloids (misfolding and aggregation of normally soluble proteins) deposit in the nephrones and cause renal failure.
- In Fabry's disease:
A deficiency of the enzyme alpha galactosidase A causes deposition of glycolipid  in the nephrones and cause renal failure.
- In Fibrillary immuno-tactoid glomerulopathy:
Fibrills (larger than amyloids) deposit in subendothelial  and mesangium of the nephrones and cause function impairment.
-  In Collagenofibrotic glomerulopathy:
Type III collagen fibers deposit in the subendothelial  and mesangium in the kidney.

# 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
- In Amyloidosis:
- Typical green birefringence under polarized light after Congo red staining (appears in red under normal light)
- In Fabry's disease:
- Hypertrophic podocytes of glomerul, foamy appearing vacuoles and mesangial widening. Vacuolated cells will be seen in PAS stain.
- In Fibrillary immuno-tactoid glumerulopathy:
- Capillary wall thickening, matrix expansion,interstitial infiltration and necrosis in renal tubules and negative Congo red stain.
-  In Collagenofibrotic glomerulopathy:
- Diffuse increase in the mesangial matrix, capillary walls widening, and collagen fibers in the glomerular basement membrane.
On electron microscopy :
-In LCDD:
- Ground-pepperlike deposits in the mesangial  and  the endothelial of the glomerular basement membrane. Also, in renal tubules if there is tubular involvement.
- In Amyloidosis:
- Endothelium, glomerular basement membrane, and podocytes thickening.
- In Fabry's disease:
- Deposition of glicolipids in lysosomes of podocytes and glomerular parietal epithelial cells.
- In Fibrillary immuno-tactoid glomerulopathy:
- Predominant fibrils in the subepithelial of glomerular capillary.
-  In Collagenofibrotic glomerulopathy:
- Deposition of irregular collagenous fibers in the mesangium and subendothelial space of the renal glumerol.

# Genetics
- Fabry's disease is transmitted in X-linked recessive pattern.
- Hereditory types of amyloidosis is transmitted in autosomal dominant pattern.
- There exact genetic association for LCDD, Fibrillary immuno-tactoid glumerulopathy, and Collagenofibrotic glomerulopathy are unknown.

# Causes
The specific etiology that cause extra or abnormal production of fibrills and chains in the glomerular depositional diseases is unknown.

# Differentiating  from Other Diseases
Glomerular deposition disease should be differentiate from other causes of glomerular disease. The various types of glomerular diseases may be differentiated from each other based on associations, presence of pitting edema, hemeturia, hypertension, hemoptysis, oliguria, peri-orbital edema, hyperlipidemia, type of antibodies, light and electron microscopic features. The following table differentiates between various types of glumerular diseases:
Some infectious diseases such as HIV, HBV, HCV, syphilis, leprosy, malaria, and schistosomiasis may cause glomerular diseases.

# Epidemiology and Demographics
The incidence of glomerular deposition disease depends on the type of the disease. Collagenofibrotic glomerulopathy and Fibrillary immuno-tactoid glumerulopathy are rare. LCDD is unknown. Most of the patients are men with the mean age of  58 years . The incidence of amyloidosis is 1.2 per 100,000 individuals per year . The incidence of Fabry's disease is 1 in 50,000 males .
Renal involvement is the most common cause of mortality and morbidity in these patients. Survival varies between months to 10 years in patients with LCDD  .

# Risk Factors
There are no established risk factors for glomerular deposition disease.

# Screening
There is insufficient evidence to recommend routine screening for glomerular deposition disease.

# Natural History, Complications, and Prognosis
If left untreated, most of the patients will suffer from ESRD in the future.
Common complication of glomerular deposition diseases is renal failure.
Prognostic factors of glomerular deposition diseases include:
- Age
- underlying hematologic disease
- Light chain deposition in other organs
- Renal function
- other medical diseases like diabetic nephropathy
Prognosis is generally not good. The median time to progression to chronic renal failure in LCDD 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
- Biopsy is the gold standard test for the diagnosis of glomerular deposition disease.

## History and Symptoms
Usually patients are asymptomatic in early stages. Symptoms are nonspecific like fatigue and weight loss. In case of edema patients may come with edema. Patients may come with abdominal pain because of deposition of light chains in the liver may lead to hepatomegaly, portal hypertension and liver failure. Patients may come with palpitation because the heart is affected in up to 80% of patients with LCDD, and may cause arrhythmias restrictive cardiomyopathy, cardiomegaly, and congestive heart failure.

## Physical Examination
- Physical exam is normal most of the time.
- Sometimes there is an organomegaly which depends on involvement of the organ like hepatomegaly

## Laboratory Findings
Laboratory findings consistent with the diagnosis of glomerular deposition disease include:
- Proteinuria (30-50% of cases have nephrotic syndrome)
- Hematuria (usually microscopic)
- Abnormal liver enzyme ( in case of liver involvement)
- Presence of a monoclonal protein in serum or urine

## Electrocardiogram
Arrhythmia like atrial fibrillation ( in case of heart involvement).

## X-ray
There are no x-ray findings associated with glomerular deposition disease.

## Echocardiography or Ultrasound
- Echocardiography:
Echocardiography may be helpful in the diagnosis of glomerular deposition disease. Findings on echocardiography suggestive of glomerular deposition disease in case of heart involvement include:
- Low EF
- Diffuse hypokinesia
- Left ventricular concentric hypertrophy
- Low diastolic compliance
- Ultrasound:
There are no ultrasound findings associated with glomerular deposition disease.

## CT scan
- There are no CT scan findings associated with glomerular deposition disease.
- In severe cases the size of the organ will increase.

## MRI
- There are no MRI findings associated with glomerular deposition disease.
- In severe cases the size of the organ will increase.

## Other Imaging Findings
There are no other imaging findings associated with Glomerular deposition diseases.

## Other Diagnostic Studies
There are no other diagnostic studies associated with Glomerular deposition diseases.

# Treatment
Medical therapy:
70% of cases untreated patients will become to ESRD. There is no standard treatment for Glomerular deposition diseases. Medical therapy options for LCDD include:
- Symptomatic treatment for renal dysfunction like ACE inhibitors like Lisinopril 2.5 to 5 mg orally once a day ( dose depends on the level of the kidney damage).
- If patient has LCDD and Multiple Myeloma (MM), should receive treatment per MM guideline like Bortezomib1.3 mg/m^2 IV on days 1,4,8,11,22,25,29,32 of 42 day cycle for cycles 1-4.
- High-dose melphalan in conjunction with autologous stem cell transplantation

## Surgery
Surgery is not the first-line treatment option for patients with glomerular deposition disease. Surgery is usually reserved for patients with either:
- LCDD patients who have detectable light chains in urine or serum
- ESRD

## Primary Prevention
There are no established measures for the primary prevention of Glomerular deposition diseases.

## Secondary Prevention
There are no established measures for the secondary prevention of Glomerular deposition diseases.