Glomerulopathy | nephron inflammation disorder

Glomerulopathy is a cluster of diseases that attack the glomerular part of the nephron. It may be produced by inflammation or not. If it caused inflammation in the nephron of the kidney then it is called glomerulitis. If the condition is non-inflammatory then it is called glomerulopathy.

It has main three types.

  • Immunotactoid Glomerulopathy
  • Fibronectin Glomerulopathy
  • Complement 3 Glomerulopathy

Immunotactoid glomerulopathy

It is disease that causes failure normal function of kidney and kidney does not perform its normal work. Immunotactoid made of two different word immuno and tactoidimmuno is related to immune system and tactoid means rod like structures which are hallow in center.

When immune system produced antibodies and these antibodies are stored in kidney abnormally it called Immunotactoid and termed glomerulopathy is define disease that involves in damaging of small filtering unit of kidney. Immunotactoidglomerulopathy first of all observed in1977 by Roseman and Eliakim they stated that this glomerular damage present in 45 year old woman .Glomeruli play a role in purification of red blood cell and production of urine take place .

This urine is made up of body waste product and water after filtering blood . The role of glomeruli is similar to water filter that trap waste material from water and pure  water .Similarly role of glomerular portion of  kidney is to clean blood it act as filtration barrier that cannot allow important material like cell and protein to pass from filter .

Proteins and cell remain in blood due to  filtration obstacle in kidney filter normally f of kidney filter do not allow cell and other protein to entering In urine when filer damages the protein become able to cross filter and enter urine in other word function of kidney is similar to coffee filter when coffee filter cut the debris of coffee come into cup of coffee. So, when the kidney filter fails from doing proper work of filter barrier then protein go into the urine, and body waste much protein.

Diagnosis

Diagnosis of this disease is done by biopsy .Biopsy is test in which pathologist took tissue form kidney and observed it under microscope the different cell of kidney .Pathologist use different microscope to see different cell in kidney and use different microscope that has magnification power 10 to100time but Immunotactoid glomerulopathy disease is diagnosed by using electron microscope that has magnification power 10000time or more.

Kidney cell are taken and observed under electron microscope they looked like rod shape pipes   which are appear hallow in center. Some evidence suggests that these rod like structure composed from immunoglobulin. Special stain (color) that are used for detection of immunoglobulin. If we observed immunoglobulin, then we say that this patient is suffering from Immunotactoid disease and Immunotactoid disease is confirmed. immunoglobulin is antibody that collect in kidney

 Cause

Exact cause of this disease is not known and this disease is not found at large level .It is a very rare disease  and present in 50 year old individual when hundred people tested then   only one person that affected with Immunotactoid glomerulopathy some evidence prove that Immunotactoid glomerulopathy caused due to lymph proliferate and leukemia that cause production of abnormal cell of immune system that lead to production  of antibody immunoglobulin that store in kidney and produce harm in filter of kidney. This disease is also caused due to hepatitis c virus.

Patient suffer from immunotactoid glomerulopathy disease contain a great chance to fall in chronic lymphatic leukemia and B cell lymphomas like disease. 

 Symptoms

There are many symptoms of this disease patient suffer with this disease release of protein take place during urination. There is swelling in legs and ankle. Other symptom like kidney dysfunction high blog pressure red blood cell also released during urination. There are also feel pain in body.   weight of patient decreases gradually, and bleeding easily start even brushing

 Treatment                                                                                         

There is no single effective treatment of this disease. Patients who are suffering with Lymph prolipherative are treated by chemotherapy that improve kidney work capacity and patients without perioperative disease their treatment is done by using medicine that effect on immune system .

These medicine break down  the immune cell that are deposit in kidney some patient do not improve by using therapy they are suffering with permanent kidney failure the end stage of this disease is ESKD.The patient with ESKD are treated by replacement therapy like transplant of kidney or dialysis . Patient with this disease are successfully transplanted but rate of recurrence remains unclear du to rarity of this disease.  

Fibronectin Glomerulopathy

It is a disease in which failure of kidney take place and chance of this disease in early and mid of juvenile period and take place in any age. It is last stage of failure of kidney and it is also non reversible.

Diagnosis  

Diagnosis of this disease is done by renal biopsy. It is process in which little piece of kidney is taken from body and observed under microscope this test exhibit that glomeruli have reactivity for those proteinic play role in immunity. Electron microscope exhibit that deposits are present in subendothelial space.Small bead like structure store in glomerular part of kidney.

Cause 

The main cause of this disease is production of mutation in gene called fibronectin 1. Production of Fibrenectin1 protein take place after information of gene fibronectin.                                                                                                    FN 1 gene play role in continuous formation of extracellular matrix of which is complex network of fibronectin protein and another cell which are play an important in formation of empty place in cell. Fibronectin protein that has high molecular weight its weight nearly 440 kilo Dalton.

It binds with integral protein that is called membrane spanning receptor protein. Fibronectin also make a connection with other protein like heparin collagen and fibrin these proteins are called extracellular matrix protein. The production Fibronectin protein take place and it diffuse outside and production of space took place.

The disease is start when fibronectin1 gene start to produce abnormal protein and this protein is begun to store in glomerular portion of kidney and body try to expel out as waste product. When fibronectin increase in large quantity in glomerular portion of kidney and extracellular matrix do not remain strong to support blood capillary because changed fibronectin do not help to make emptiness in extracellular matrix .

When extra cellular become so weak ,so they do not support glomeruli to expel out waste product or in other word the efficiency of glomeruli to filter blood decrease as a result that the substances present in body for normal function like protein may go out from body during the process of urination and blood do not purify properly due to weakness of filter present in kidney after some time filtration power of kidney decrease and kidney do not perform its function for long time and go at last stage .

This disease is caused du to change in FN1 but  40% disease caused by mutation in FN1 gene and other cause of this disease do not known. This disease is also called autosomal inherited disease because FN1 is autosomal gene one copy of mutant gene is enough for creation of this disease some people changed FN1 gene, but they do not suffer from this disease this condition called reduction in inheritance fibronectinglomerulopathy is caused due heterozygous mutation inY973C when genetic analysis perform

Frequency

Small quantity of people has this disease only 45 cases reported in science and prevalence of this disease is not known.

Symptom

The patient is suffering from fibronectin have high level of blood pressure and there is removal of protein and blood from body during urination and acid are store in renal tubule of kidney because capacity of kidney for removing acid decrease

Treatment

Treatment of this disease is absent. There issue of antiproteinuric and Reno protective treatment With ACE inhibitor antiAT1R antagonistic that help in slow down process of renal failure. Some other treatment of this disease like dialysis or transplant.

C3 Glomerulopathy

It is also called C3G .C3 is a protein and G is stand for glomerulopathy It is group of disease that caused due malfunction of kidney C3 is a protein which play a key role in immunity glomerular is defined that glomerular filter do not perform their function with suitable way. It is also rare disease like other and long-term disease.

The old name of C3G is membranoproliferative glomerulonephritis. C3G is divided in to two type first is dense deposit disease and DDD is its abbreviation and second type is C3glomerulonephritis and its abbreviation is C3GN. Before 2013 name of dense deposit disease is called MPGN type 1 and patient who are suffer from MPGN type 2and type 3 we say that they are suffer with C3GN .

C3G is a part of immune system and it consist protein which play role in destroying the bacteria and virulent particle which cause disease in your body compliment system is divided in to three pathway ,the first pathway is named classical pathway second one is lectin pathway and third pathway called alternative pathway .

When any threats found like virus or bacteria attack on body classical and lectin pathway on or off as need but alternative pathway is never off for one second because its fight with powerful threats but this pathway perform their function under control of body .Some time it is not control by body and break down healthy cell of body and this produce disease which is known C3G.

Types of C3G

There are two type of C3G

Dense deposit disease 

The disease in which C3 protein collect to gather in one part of glomeruli of kidney and glomeruli become thick it is called dense deposit disease

C3 glomerulonephritis

 It is opposite of DDD in this disease C3 protein do not store one place and it spread out and glomeruli become thin.

 Symptom

There are many symptoms of this disease. Its symptom is like another kidney disease. First, bleeding in urine during urination and color of urine become pink or cola color. Other symptom of this disease is protein in urine and color of urine foamy cloud and amount of urine decrease. There are swelling in different body part like face legs and feet ankle because C3 protein fluid filled in these part and cause swelling. Blood pressure of patient become too high and ability of alertness decrease.

Body feel pain because filtration power of kidney decrease, and nitrogenous waste remain in body and patient feel discomfort in case of DDD lipid present in small quantity in face and C3 store behind eye and produce difficulties in vision

Causes

 The exact cause of this disease is unknown, but some researcher said that when specific part of immune system name alternate pathway does not perform its function with proper way then C3G disease produced.

When body do not control alternate pathway then alternate pathway perform work at high rate and large amount of C3 protein accumulate in glomerular filter of kidney that is harmful for kidney and become a cause of C3G disease. This disease caused due to genetic and acquired factor.

Genetic risk factor

It is based on DNA. This disease came from your parents through DNA.DNA has gene which play role in body it is also called genetic code if any change take place in gene alternate system do not perform it function with suitable way and C3G cause

Acquired risk factor

 The factor that not from your parent and these factors came after baby birth in this case antibody which are protein in nature and help immune system to kill bacteria and viruses but some time abnormal antibodies production take place in people that become main cause of C3G.

There are two abnormal antibodies discovered that cause of C3Gone is autoantibodies that invade cell of body and body cell destroy. When body cell destroys the control of body on alternate pathway finished and function of alternate pathway disturbed and C3G taken place Other antibodies that cause C3G is paraprotein that not invade on body part but alternate system react with it that is harmful for body .These two antibodies play role in loss control of alternate system and more activation of alternate system that is harmful for kidney and injury take place in kidney

Diagnosis

 There are many tests perform to diagnosis to C3G disease. First, your doctor checks your serum creatinine level in blood to observed condition of kidney. Creatinine is produced during metabolism of muscle as a waste product.

Kidney filter creatinine and level of creatinine remain normal in blood if creatinine level increased in blood it means kidney do not perform its function properly. Doctor also use your serum creatinine relate other factor like age to check filtration rate of glomeruli of kidney doctor also perform test of urine to check that protein may expel during urination if urine has protein it is clear that kidney problem is confirmed and your doctor also recommended some other test like biopsy test and complement system test

Complement system test

 This test is done to determine C3G disease .In this test doctor check different part of complement system .First doctor measure complement protein in blood,level of protein in blood decide alternate system perform work normally or over active .This test is used to determine that  antibody like C3nephratic factor is not involved to produce problem in glomeruli filter of kidney. Genetic mutation test performs to see that change in gene that produce more activity in alternate system

Kidney biopsy test

 In this test small amount of tissues are taken from kidney and observed under microscope to search out what is occur  in kidney or used to observe that glomeruli filter perform its work accurately or some problem happen .

Biopsy test is not possible in some patient so doctor perform other test to diagnose C3G immunofluorescence test is also used to diagnose C3G disease. When doctor perform this test, they also used color to light up C3 protein in glomeruli of kidney if massive amount of C3protien in glomerular filter of kidney is present then C3G disease is confirmed. There are two type of biopsy test.

Needle biopsy

During this biopsy needle are taken and place on those part of skin where kidney present and small simple of kidney tissue taken through these needles.

Open biopsy

 During this biopsy tissue of kidney removed directly from kidney by open surgery

Blood test

Blood test is done to diagnose C3G disease this test also tell you about complement protein level like C1, C2, C3, C4. The amount of these protein remains normal but in case of dense deposit disease amount of C4 protein start to rise up  Another protein called soluble C5b-9complement protein level is normal when patent is suffering from dense deposit disease and these protein amount start to increase during complement3 glomerulonephritis disease.

Blood test also perform to check C3nephritic factor this is an autoantibody but this attack on your body not pathogen. The presence of this factor in blood determinate that patient suffer with C3G.If C3 nephritic factor present in blood of patient it tells that patient is suffered with 80%dense deposit disease and chance of 40% complement glomerulonephritis

Treatment

There is no specific treatment of this disease some medicine is used to control reactivity of alternate system. Treatment of this disease is depending on cause when its causes is identified then treatment is start when C3G is caused due to autoantibody then immunosuppressant drug is used for treatment of this disease.

Autoantibody is produced by immune system that help to kill bacteria and viruses some time abnormal antibody produces that cause C3G and we use immunosuppressant drug to destroy these abnormal antibodies.

Some other drug use for treatment of C3G disease like glucocorticoid, rituximab, cyclophosphamide, mycophenolate inhibitor ACE corticosteroid, mofetil, sirolimus, azathioprine these drugs has effect on alternate system to remain in normal condition.

Corticosteroid

This drug decreases the activity of immune system and this drug do not allow the immune system to produce C3 protein and which do not produce cause any damage in kidney.

Inhibitor ACE

  This drug keeps blood pressure at normal and decrease losing rate of protein during urination.

Change in food

 If any changes take place in food habit this may secure kidney from harming. If person that is suffer from C3G he must use food that has low level of sodium and protein because food with less protein also produce less strain in kidney.

Plasma exchange

Body has a plasma fluid that is part of blood which has auto antibody. This fluid is exchanged with those fluid that has not harmful antibody through vein. Many patients try this treatment, but result was not good because little amount of harmful protein or auto antibody removed from body

Plasma infusion

When patient is suffered with C3G due to mutation in gene the treatment of this disease is plasma infusion. These mutations take place in gene named thrombomodulin that send signal alternate pathway to work efficiently during this process protein do not perform their function normally, so mutation of gene occurs, some protein misses and C3Gdisease caused. Plasma is entered in vein that has protein which stop C3G disease.

Its result is success fully but at limited base. Eculizumab is another drug that is used for C3G diseases. The amount of drug is depending on various factor like weight Hight and age. Sometime drug used for treatment also produce complication 

Treating condition some time occur with C3G disease

C3 protein is deposit in kidney and damage kidney. But it has bad effect on eye protein from complement system can store on back of eye area that is named fundus. These deposits are called drusen, so doctor check your eyes and start treatment.

C3 protein store behind eye so doctor use different drug to stop this storage

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