Minimal change disease
Encyclopedia
Minimal Change Disease is a disease of the kidney
that causes nephrotic syndrome
and usually affects children (peak incidence at 2–3 years of age).
(NS) in children between the ages of 1 and 7, accounting for the majority (about 90%) of these diagnoses. Among teenagers who develop NS, it is caused by minimal change disease about half the time. It can also occur in adults but accounts for less than 20% of adults diagnosed with NS. Among children less than 10 years of age, boys seem to be more likely to develop minimal change disease than girls.
People with 1 or more autoimmune disorders are at increased risk of developing minimal change disease. Having minimal change disease also increases the chances of developing other autoimmune disorders.
(leakage of protein into the urine) and edema
(water retention
). Nephrotic syndrome
(NS) is a general term that refers to the loss of protein in the urine, hypercholesterolemia, and edema. Many conditions are categorized as nephrotic syndromes—minimal change disease is unique, because it is the only one lacking any evidence of pathology on light microscopy (hence the name).
When protein is lost in the urine, the concentration of protein in the blood decreases, allowing water to move into other areas of the body, which leads to swelling known as edema
. Edema is commonly observed in the feet and legs, in the belly or abdomen (ascites), and around the eyes, but can occur anywhere, especially in response to gravity. Additionally, because of this extra fluid that stays in the body, people often gain weight and experience fatigue—in many patients, for example, their usual clothes and shoes will no longer fit. Some people notice that their urine becomes more frothy or foamy from the excess protein in the urine, and may find that they urinate less often.
(podocyte) foot processes., vacuolation, and growth of microvilli on the visceral epithelial cells.
The pathology of minimal change disease is unclear and is currently considered idiopathic
. The pathology does not appear to involve complement, immunoglobulins
, or immune complex deposition. Rather, an altered cell-mediated immunologic response with abnormal secretion of lymphokine
s by T cell
s is thought to reduce the production of anions in the glomerular basement membrane
, thereby increasing the glomerular permeability to serum albumin
through a reduction of electrostatic repulsion. The loss of anionic charges is also thought to favor foot process fusion. The etiological agent is somewhat of a mystery but viruses such as EBV
, and food allergies have been implicated. Also, the exact cytokine
responsible has yet to be elucidated, with IL-12
, IL-18
and IL-13
having been most studied in this regard, yet never conclusively implicated.
is prescribed along with a blood pressure medication, typically an ACE inhibitor
such as lisinopril
. Some nephrologists will start out with the ACE inhibitor
first in an attempt to reduce the blood pressure's force which pushes the protein through the cell wall in order to lower the proteinuria
. In some cases a corticosteroid
may not be necessary if the case of minimal change disease is mild enough to be treated just with the ACE Inhibitor
. Often the liver is overactive with minimal change disease in an attempt to replace lost protein and over produces cholesterol
. Therefore a statin
drug is often prescribed for the duration of the treatment. When the urine is clear of protein, the drugs can be discontinued. 50% of patients will relapse and need further treatment with immunosuppressants such as cyclosporine and tacrolimus
.
Minimal change disease usually responds well to initial treatment and over 90% of patients will respond to oral steroids within 6–8 weeks, with most of these having a complete remission. Symptoms of nephrotic syndrome
(NS) typically going away, but this can take from 2 weeks to many months. Younger children, who are more likely to develop minimal change disease, usually respond faster than adults. In 2 out of 3 children with minimal change disease, however, the symptoms of NS can recur, called a relapse, particularly after an infection or an allergic reaction. This is typical, and usually requires additional treatment. Many children experience 3 to 4 relapses before the disease starts to go away. Some children require longer term therapy to keep MCD under control. It appears that the more time one goes without a relapse, the better the chances are that a relapse will not occur. In most children with minimal change disease, particularly among those who respond typically, there is minimal to no permanent damage observed in their kidneys.
With steroid
treatment, the symptoms of nephrotic syndrome
(NS) will go away, called remission, in the majority of children with minimal change disease. This typically occurs faster, over 2 to 8 weeks, in younger children, but can take up to 3 or 4 months in adults. Typically the dose of steroids will initially be fairly high, lasting 1or 2 months. At some point after the urine protein levels have become normal again, the dose of steroids might be switched to an every-other-day schedule, then very slowly reduced over the course of several months. It is very important to taper, or gradually reduce, the dose of steroids. The body does not respond well to a sudden discontinuation of steroids, and this might also trigger a relapse
, or return, of NS symptoms. Giving steroids initially for a longer period of time is thought to reduce the likelihood of relapse. The majority of children with minimal change disease will respond to this treatment.
Even among those who respond well to steroids initially, it is common to observe periods of relapse (return of NS symptoms). Because of the potential for relapse, the physician may prescribe and teach the patient how to use a tool to have you check urine protein levels at home. Two out of 3 children who initially responded to steroids will experience this at least once. Typically the steroids will be restarted when this occurs, although the total duration of steroid treatment is usually shorter during relapses than it is during the initial treatment of the disease.
There are several immunosuppressive medications that can be added to steroids when the effect is not sufficient or replace them in case of intolerance or specific contraindications.
Some authors have noted that other conditions associated with T-cell abnormalities, such as Hodgkin's disease and T-cell lymphoma
, are sometimes associated with minimal change disease.
It should also be noted that minimal change disease is being seen with increasing frequency in adults over the age of 80.
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
that causes nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
and usually affects children (peak incidence at 2–3 years of age).
Epidemiology
Minimal Change Disease is most common in very young children but can occur in older children and adults. It is by far the most common cause of nephrotic syndromeNephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
(NS) in children between the ages of 1 and 7, accounting for the majority (about 90%) of these diagnoses. Among teenagers who develop NS, it is caused by minimal change disease about half the time. It can also occur in adults but accounts for less than 20% of adults diagnosed with NS. Among children less than 10 years of age, boys seem to be more likely to develop minimal change disease than girls.
People with 1 or more autoimmune disorders are at increased risk of developing minimal change disease. Having minimal change disease also increases the chances of developing other autoimmune disorders.
Symptoms
The symptoms are proteinuriaProteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
(leakage of protein into the urine) and edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
(water retention
Water retention
Water retention can refer to:*Water retention , an abnormal accumulation of fluid in the circulatory system or within the tissues or cavities of the body...
). Nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
(NS) is a general term that refers to the loss of protein in the urine, hypercholesterolemia, and edema. Many conditions are categorized as nephrotic syndromes—minimal change disease is unique, because it is the only one lacking any evidence of pathology on light microscopy (hence the name).
When protein is lost in the urine, the concentration of protein in the blood decreases, allowing water to move into other areas of the body, which leads to swelling known as edema
Edema
Edema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
. Edema is commonly observed in the feet and legs, in the belly or abdomen (ascites), and around the eyes, but can occur anywhere, especially in response to gravity. Additionally, because of this extra fluid that stays in the body, people often gain weight and experience fatigue—in many patients, for example, their usual clothes and shoes will no longer fit. Some people notice that their urine becomes more frothy or foamy from the excess protein in the urine, and may find that they urinate less often.
Pathology
For years pathologists found no changes when viewing specimens under light microscopy; hence the name minimal change disease. With the advent of electron microscopy, the changes now known as the hallmarks for the disease were discovered. These are diffuse loss of visceral epithelial cellsPodocyte
Podocytes are cells in the Bowman's capsule in the kidneys that wrap around the capillaries of the glomerulus...
(podocyte) foot processes., vacuolation, and growth of microvilli on the visceral epithelial cells.
The pathology of minimal change disease is unclear and is currently considered idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
. The pathology does not appear to involve complement, immunoglobulins
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
, or immune complex deposition. Rather, an altered cell-mediated immunologic response with abnormal secretion of lymphokine
Lymphokine
Lymphokines are a subset of cytokines that are produced by a type of immune cell known as a lymphocyte. They are protein mediators typically produced by T cells to direct the immune system response by signalling between its cells...
s by T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s is thought to reduce the production of anions in the glomerular basement membrane
Glomerular basement membrane
The glomerular basement membrane is the basal laminal portion of the glomerulus. The Glomerular capillary endothelial cells, the GBM and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that...
, thereby increasing the glomerular permeability to serum albumin
Serum albumin
Serum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
through a reduction of electrostatic repulsion. The loss of anionic charges is also thought to favor foot process fusion. The etiological agent is somewhat of a mystery but viruses such as EBV
EBV
EBV may refer to:* Epstein-Barr virus, a virus of the herpes family* EBV infectious mononucleosis, mononucleosis caused by the Epstein-Barr virus* Escuela Bella Vista, an American school located in Maracaibo, Venezuela...
, and food allergies have been implicated. Also, the exact cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
responsible has yet to be elucidated, with IL-12
IL-12
IL-12 or IL 12 can refer to:Medicine* Interleukin 12Airplanes* Ilyushin Il-12Politics* Illinois' 12th congressional districtRoads* Illinois Route 12...
, IL-18
IL-18
IL-18, IL 18 or IL18 may refer to:* Interleukin 18, a protein encoded in humans by the IL18 gene* Ilyushin Il-18, a Cold War–era Soviet airliner and military transport* Illinois's 18th congressional district...
and IL-13
IL-13
IL-13 or IL 13 can refer to:* Interleukin 13* Illinois' 13th congressional district* Illinois Route 13...
having been most studied in this regard, yet never conclusively implicated.
Genetics
Protein tyrosine phosphatase receptor type O - also known as glomerular epithelial protein 1 [GLEPP1] has been shown to be mutated in a number of cases.Treatment
PrednisonePrednisone
Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...
is prescribed along with a blood pressure medication, typically an ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
such as lisinopril
Lisinopril
Lisinopril is a drug of the angiotensin-converting enzyme inhibitor class that is primarily used in treatment of hypertension, congestive heart failure, and heart attacks and also in preventing renal and retinal complications of diabetes. Its indications, contraindications and side effects are as...
. Some nephrologists will start out with the ACE inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
first in an attempt to reduce the blood pressure's force which pushes the protein through the cell wall in order to lower the proteinuria
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
. In some cases a corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...
may not be necessary if the case of minimal change disease is mild enough to be treated just with the ACE Inhibitor
ACE inhibitor
ACE inhibitors or angiotensin-converting enzyme inhibitors are a group of drugs used primarily for the treatment of hypertension and congestive heart failure...
. Often the liver is overactive with minimal change disease in an attempt to replace lost protein and over produces cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
. Therefore a statin
Statin
Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the...
drug is often prescribed for the duration of the treatment. When the urine is clear of protein, the drugs can be discontinued. 50% of patients will relapse and need further treatment with immunosuppressants such as cyclosporine and tacrolimus
Tacrolimus
Tacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...
.
Minimal change disease usually responds well to initial treatment and over 90% of patients will respond to oral steroids within 6–8 weeks, with most of these having a complete remission. Symptoms of nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
(NS) typically going away, but this can take from 2 weeks to many months. Younger children, who are more likely to develop minimal change disease, usually respond faster than adults. In 2 out of 3 children with minimal change disease, however, the symptoms of NS can recur, called a relapse, particularly after an infection or an allergic reaction. This is typical, and usually requires additional treatment. Many children experience 3 to 4 relapses before the disease starts to go away. Some children require longer term therapy to keep MCD under control. It appears that the more time one goes without a relapse, the better the chances are that a relapse will not occur. In most children with minimal change disease, particularly among those who respond typically, there is minimal to no permanent damage observed in their kidneys.
With steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
treatment, the symptoms of nephrotic syndrome
Nephrotic syndrome
Nephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
(NS) will go away, called remission, in the majority of children with minimal change disease. This typically occurs faster, over 2 to 8 weeks, in younger children, but can take up to 3 or 4 months in adults. Typically the dose of steroids will initially be fairly high, lasting 1or 2 months. At some point after the urine protein levels have become normal again, the dose of steroids might be switched to an every-other-day schedule, then very slowly reduced over the course of several months. It is very important to taper, or gradually reduce, the dose of steroids. The body does not respond well to a sudden discontinuation of steroids, and this might also trigger a relapse
Relapse
Relapse, in relation to drug misuse, is resuming the use of a drug or a dependent substance after one or more periods of abstinence. The term is a landmark feature of both substance dependence and substance abuse, which are learned behaviors, and is maintained by neuronal adaptations that mediate...
, or return, of NS symptoms. Giving steroids initially for a longer period of time is thought to reduce the likelihood of relapse. The majority of children with minimal change disease will respond to this treatment.
Even among those who respond well to steroids initially, it is common to observe periods of relapse (return of NS symptoms). Because of the potential for relapse, the physician may prescribe and teach the patient how to use a tool to have you check urine protein levels at home. Two out of 3 children who initially responded to steroids will experience this at least once. Typically the steroids will be restarted when this occurs, although the total duration of steroid treatment is usually shorter during relapses than it is during the initial treatment of the disease.
There are several immunosuppressive medications that can be added to steroids when the effect is not sufficient or replace them in case of intolerance or specific contraindications.
Other notes
80% of those who get minimal change disease have a recurrence.Some authors have noted that other conditions associated with T-cell abnormalities, such as Hodgkin's disease and T-cell lymphoma
T-cell lymphoma
The T-cell lymphomas are the four types of lymphoma that affect T cells. These account for perhaps one in ten cases of non-Hodgkin lymphoma.They can be associated with Epstein Barr virus and Human T-cell leukemia virus-1.-Types:The four classes are:...
, are sometimes associated with minimal change disease.
It should also be noted that minimal change disease is being seen with increasing frequency in adults over the age of 80.
External links
- Kidcomm – An online resource for parents dealing with childhood kidney diseases
- National Kidney Foundation
- Associazione sindrome nefrosica italia onlus – Italian organization dedicated to support patients and parents dealing with nephrotic syndrome
- UNC Kidney Center – Minimal Change Disease