Idiopathic nephrotic syndrome

French national reference center for idiopathic nephrotic syndrome (INS)

The « idiopathic nephrotic syndrome (INS) in children and adults » reference center, whose coordinator is Pr Audard (Henri-Mondor hospital), was created in 2006. It was re-labeled following the evaluation of a jury mandated by the DGOS (ministerial order of May 9, 2017).

The reference center is made up of a coordinating center, 4 constituent reference centers and 23 competence centers, thus ensuring the networking of the entire territory.

The INS reference center aims to continue the work initiated more than 10 years ago in the fields of care, expertise, medico-social and therapeutic education.

This center of reference is affiliated to the ORKID rare diseases healthcare network and the ERKNet european reference network (ERN).

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Medical
team

Pr Knebelmann

Head of the reference center
Pr Bertrand Knebelmann
MD, PhD

Pr Olivia Gillion Boyer, néphrologue pédiatre

Pr Olivia Boyer
MD, PhD

Contact us
 

For a child :
Phone. +33 (0)1 44 49 44 67

Doctolib : prenez rendez-vous en ligne

For an adult patient :
Phone. +33 (0)1 44 49 54 16

Doctolib : prenez rendez-vous en ligne

In case of emergency

Idiopathic nephrotic syndrome in children

What is idiopathic nephrotic syndrome in children?

The kidneys contain glomeruli that filter the blood, functioning like « noodle sieves », retaining large substances (proteins and blood cells) and letting through waste products, small substances mostly from food, such as water, salt, urea. These filtered wastes are then found in the urine.

Schema SNI anglais 1A nephrotic syndrome occurs when the holes in the sieve of the glomeruli widen, allowing proteins, mainly albumin (albuminuria), to pass into the urine. The result is a decrease in the concentration of albumin in the blood, which normally ensures the maintenance of water and salt in the blood through a « sponge » effect. The water and salt will then pass from the bloodstream to the rest of the body and cause edemas.

In children, nephrotic syndrome is most often related to what is called idiopathic nephrotic syndrome (the cause of which is not known), also known as nephrosis.

There are two forms of idiopathic nephrotic syndrome based on response to treatment :

  • Steroid sensitive nephrotic syndrome when standard treatment with cortisone (prednisone) achieves complete remission, i.e. making the filter impermeable to protein again and making the protein disappear in the urine; and conversely
  • Steroid resistant nephrotic syndrome (See SRNS sheet in French).

Idiopathic nephrotic syndrome « responds » eight times out of ten to cortisone. The disappearance of proteinuria is quickly accompanied by the disappearance of edemas.

How common is idiopathic nephrotic syndrome in the population?

It is a rare disease that affects about 1 to 5 children per 100,000. The disease is more common in boys than in girls.

What are the causes and means of transmission of idiopathic nephrotic syndrome?

Idiopathic nephrotic syndrome is a disease of which the precise cause is not known.

Nephrotic syndromes that are put into remission with immunosuppressive treatment seem to be linked to an abnormality in the cells of the immune system (white blood cells) which would manufacture one or more products circulating in the blood, which would increase the permeability of the glomerular filter to proteins (widening of the holes in the sieve). The cause(s) of this immune dysfunction are currently not identified.

Conversely, about one-third of nephrotic syndromes that do not go into remission with immunosuppressive therapy have a genetic origin most often related to structural abnormalities of certain proteins in podocytes (glomerular filter cells) (see Hereditary SRNS sheet, Congenital NS sheet).

However, all the genetic causes of steroid-resistant nephrotic syndrome are not yet known.

What are the symptoms of idiopathic nephrotic syndrome?

A nephrotic syndrome is suspected when there is edemas, responsible for puffiness of the eyelids in the morning and swelling of the ankles during the day when standing.

Too much water and salt in the body can also cause swelling of the abdomen (ascites), bursa in boys (hydrocele), water accumulation around the lungs (pleural effusion). These edemas are troublesome, but most often they are not dangerous.

Faced with these edemas, it is easy to affirm that it is a nephrotic syndrome by looking for the presence of proteins in the urine.
In other cases, there are no symptoms and the diagnosis is made by chance during a blood or urine test.

Finally, it can be revealed by various complications: abdominal pain, shortness of breath, infection, headaches, clots in the circulation (thrombosis) that can move and cause a clot in the lungs (pulmonary embolism).

What tests should be taken for the diagnosis?

When the diagnosis is suspected, the urine is tested for protein. When the test strip is positive for protein, it is important to specify the amount of protein lost in the urine. This can be done in the laboratory on a morning sample or on a urine collection for 12 or 24 hours.

The diagnosis is then confirmed by a blood test. Many diseases affecting the kidneys can be responsible for edemas and proteins in the urine. For this reason, specialized examinations may be necessary.

Thus, a kidney biopsy may be indicated at the time of diagnosis if there are clinical symptoms or biological findings suggesting that the nephrotic syndrome is related to another disease. It is also indicated in children who still retain protein in the urine after one month of treatment with corticosteroids (See steroid-resistant nephrotic syndrome fact sheets).

Which organs are affected?

Apart from edemas, which are often unsightly but usually without severe consequences (and which leave no traces), the nephrotic syndrome exposes to certain complications.

Infections

  • Bacterial infections are common and can occur early in the course of the disease. They may include peritonitis (infection around the intestines) leading to severe abdominal pain and fever, meningitis, pneumonia or cellulitis (infection of the subcutaneous tissues). All of these infections can be controlled with antibiotics.
  • Viral infections can also be favored by treatment given to treat nephrotic syndrome, such as prednisone or immunosuppressants. This is particularly the case with chickenpox which can be serious. There are effective medicines that should be given if chickenpox occurs to prevent complications of the disease, and if you come into contact with someone with chickenpox to prevent its occurrence.

Thromboses

Nephrotic syndrome is responsible for coagulation abnormalities that increase the risk of blood clots forming in the circulation. These are thrombosis accidents that can be localized in the veins of the arms or legs, renal veins, brain vessels, pulmonary arteries. These accidents can be prevented by taking medicines called anticoagulants (which thin the blood).

Other complications

When the treatments are not effective and do not lead to remission (complete disappearance of proteins in the urine), urine protein leakage can be responsible, in the long term, for a state of malnutrition with muscle wasting, height growth disorders, disturbances in lipid profile and thyroid dysfunction. Scars may appear and progress in the kidneys, leading to chronic kidney failure within an unspecified period of time, which may be several years.

What are the treatments to follow?

The treatment has two goals :

limit the consequences of the nephrotic syndrome, in particular edemas, and make proteinuria disappear.

Edemas are the consequence of a decrease in the elimination of salt by the kidneys. The diet should therefore be as low in salt as possible. Salt-rich foods should be avoided and no salt should be added to food at mealtimes. Diuretics, drugs that increase salt elimination by the kidneys, should be used with caution as they can promote the formation of clots in the bloodstream. Albumin infusions are rarely necessary.

In order to regress proteinuria, treatment is based on corticosteroid therapy: prednisone (Cortancyl®) or a drug of the same family, such as prednisolone (Solupred®). It is associated with a diet limited in salt, sugars and fats, and a supplementation of calcium and vitamin D (see below).

If proteinuria persists after one month, three infusions of high doses of corticosteroids (prednisone equivalent, administered intravenously) are given, each 48 hours apart. If the proteinuria persists one week after the infusions, the nephrotic syndrome is said to be “steroid-resistant”. (see sheets in French)

Two in three children with steroid-sensitive nephrotic syndrome will have one or more relapses when the dose of prednisone is lowered or after stopping treatment. They are often favored by an infection such as nasopharyngitis or angina. Recovery, either spontaneously or by antibiotic therapy, of the infectious episode can lead to remission.

It is sometimes suggested that corticosteroid therapy be given daily during infections to prevent relapse. An allergy can also be a factor in relapse. Relapse treatment consists of increasing the corticosteroid therapy, which is given daily until remission is achieved, then given again every other day at a decreasing dose.

If the dose of prednisone necessary to maintain remission is too high causing a risk of significant side effects, the use of other immunosuppressive treatments (i.e. based on molecules that limit the action of white blood cells) is necessary. These are in particular levamisole (Elmisol®), mycophenolate mofetil (Cellcept®), cyclosporine (Neoral®) and tacrolimus (Prograf®), cyclophosphamide (Endoxan®), rituximab (Mabthéra®). Other treatments being evaluated may be offered.

There is no treatment allowing a total cure in all patients at this time.

What are the side effects of steroids?

Steroids and other drugs used have potential side effects.

The side effects of prednisone treatment depend on the dose the child receives, but also vary from child to child for the same dose, with some children more likely to develop a complication than others. As the dose decreases, especially when the treatment is given every other day, the side effects also decrease.

Possible side effects include :

  • Change in physical appearance :

Red cheeks, increased hairiness. The skin is more fragile. Teens can develop stretch marks and acne, for which the advice of a dermatologist is helpful.

  • Appetite stimulation :

Corticosteroid therapy can cause rapid and unbalanced weight gain, with big cheeks and a big belly. A diet low in sugar and fat must be followed to avoid excessive weight gain. Eating outside of mealtimes should be avoided. Reducing sugar consumption is recommended: elimination of rapidly absorbed sugars, sweets, cakes, chocolate, jams and sweetened drinks. Avoiding high-fat foods by reducing butter and cheese is also recommended.

  • Character disorders :

Children receiving prednisone are often very active, restless. They may have temper tantrums and trouble sleeping. Some children are sadder. They may be aggressive when they used to be very calm children. These problems disappear when the doses of prednisone are reduced.

  • Increase in blood pressure :

This is why the diet should be low in salt even when the proteinuria has subsided. It is only when the steroid dose is low that salt intake can be increased.

  • Height growth disorders :

Steroids, especially in high doses and given daily, block growth. It restarts when the doses are decreased and especially when the treatment is given every other day. If the doses needed to keep the child in remission are too high and are responsible for slowing growth, the doctor may decide to introduce another treatment.

  • Less resistance to infections :

Treatment with prednisone decreases the immune system. In case of fever, a doctor should be consulted promptly.

  • Bone problems :

Steroid treatment can be responsible for calcium loss in the bones (osteoporosis), which is why a calcium and vitamin D supplement is often prescribed. Disorders of the vascularization of certain areas of the bones (osteonecrosis) may occur and result in pain. Immobilization in a cast may then be necessary.

  • Eye problems :

Prolonged treatment can cause a cataract, which can be detected by an ophthalmologic examination before it leads to blurred vision.

  • Problems when stopping treatment :

After prolonged treatment, its abrupt cessation can have serious consequences because the body no longer produces enough cortisol, the natural equivalent of prednisone. In these cases, hydrocortisone replacement therapy may be necessary for a few weeks.

How does steroid sensitive nephrotic syndrome progress in the long term, in adulthood?

The disease may last longer if the nephrotic syndrome started early in childhood, before 4 to 5 years old.

However, the number of relapses each year tends to decrease over time. It is impossible to predict how long the illness will last. There is definitely a risk that the disease will continue to relapse into adulthood. About 40% of people who had multiple relapses in childhood continue to have relapses into adulthood.

As long as the nephrotic syndrome continues to respond to treatment, which is most often the case, there is virtually no risk of the disease becoming complicated by chronic kidney failure.

How is idiopathic nephrotic syndrome in children monitored?

At home, the child and his parents should test daily or every two to three days for proteins in the urine (proteinuria).

The simplest way to do this is to use strips, such as Albustix®, which are dipped in urine and then compared with the color of the strips indicated on the bottle. The color of the strip will change from yellow when there is no proteinuria to light or dark green depending on the degree of proteinuria.

We can thus know if this search for proteinuria is negative or positive, with a scale of one, two, three or four crosses. The presence of « traces » should not be a cause for concern. The results are noted in a follow-up booklet.

When the protein test strip is positive, it is important to specify the amount of protein lost in the urine. This can be done in the laboratory on a urine collection.

The advantage of regular urine monitoring with the Albustix® strip is that it can detect a relapse long before edemas occur. Treatment is then started quickly to limit the consequences of this relapse. In addition, remission is achieved more quickly if the relapse is treated without delay.

In addition to regular monitoring of proteinuria and blood albumin levels, the doctor regularly checks growth, kidney function (urea and blood and urine creatinine), and immunosuppressive drug dosages.

Monitoring also concerns the child’s weight, which may increase in case of edemas or due to steroid therapy which stimulates the appetite.

Steroid resistant nephrotic syndrome

What is steroid resistant nephrotic syndrome?

The kidneys allow, thanks to glomeruli, a kind of filter or « waste sorting plant », to eliminate certain components present in the blood and coming mainly from food, such as water, salt, urea from proteins present in meat or dairy products. This filter is very selective and does not let through certain substances such as proteins produced by the body.

A nephrotic syndrome occurs when this filter is too permeable and the kidneys allow large amounts of protein, especially albumin, present in the bloodstream to pass through the urine. The result is a decrease in the concentration of albumin in the blood and a difficulty for the kidneys to eliminate salt and water from the diet. Water and salt will pass from the bloodstream into the tissues and cause edemas.

Nephrotic syndrome is said to be steroid resistant when the standard treatment of nephrotic syndrome with cortisone (prednisone) does not achieve complete remission, i.e. to make the filter impermeable again to proteins and to remove the proteins in the urine.

How common is steroid resistant nephrotic syndrome in the population?

The exact number of new cases annually in the general population is unknown. All nephrotic syndromes affect 1 to 4 in 100,000 children, and 5 to 10% of them are steroid resistant.

What are the causes and means of transmission of the steroid resistant nephrotic syndrome?

Sporadic steroid resistant idiopathic nephrotic syndrome is a heterogeneous disease. Approximately one third has a genetic origin most often related to structural abnormalities of certain proteins in podocytes (cells of the glomerular filter). (see https://www.filiereorkid.com/la-fonction-renale/). All the genetic causes of steroid resistant nephrotic syndrome are not yet known.

The others have a totally different and yet unsolved mechanism. One of the hypotheses put forward is that the cells of the immune system produce one or more circulating factors that increase the permeability of the glomerular filter to proteins.

Current research focuses on the search for new genes and the identification of circulating factors responsible for nephrotic syndrome.

What are the symptoms of steroid resistant nephrotic syndrome?

A nephrotic syndrome is suspected when there are edemas, responsible for puffiness of the eyelids in the morning, swelling of the ankles during the day when standing. Excess water and salt in the body can also cause swelling of the abdomen (ascites), bursae in boys (hydrocoele), an effusion in the pleura surrounding the lungs (pleural effusion). These edemas are bothersome, but most often are not dangerous.

Faced with these edemas, one can easily affirm that it is a nephrotic syndrome by looking for the presence of proteins in the urine.

In other cases, there are no symptoms and the diagnosis is made incidentally during a blood or urine test.

Finally, it can be revealed by various complications: abdominal pain, shortness of breath, infection, headaches, clots in the circulation (thrombosis) that can move and lead to a pulmonary embolism.

What tests must be taken for the diagnosis?

When the diagnosis is suspected, we look for proteins in the urine. The simplest way to do this is to use strips, such as Albustix®, which are dipped into the urine and then compared in color with those on the vial. The color of the strip will change from yellow when there is no proteinuria to light or dark green depending on the degree of proteinuria. This will indicate whether the proteinuria test is negative or positive on a scale of one, two, three or four crosses. The presence of « traces » should not be a cause for concern.

When the protein test strip is positive, it is important to specify the amount of protein lost in the urine. This can be done in the laboratory on a morning sample or on a 12-hour or 24-hour urine collection.

The diagnosis is then confirmed by a blood test, usually followed by a kidney biopsy, and a genetic analysis that takes several months. All the genetic causes of steroid resistant nephrotic syndrome are not yet known.

What are the treatments to follow?

The treatment has two goals: to make the proteinuria disappear and to limit the consequences of the nephrotic syndrome, in particular edemas.

In order to regress proteinuria, immunosuppressive treatments, particularly cyclosporine and tacrolimus, can have a beneficial effect in combination with steroids (prednisone). Other treatments are currently being evaluated and may be proposed.

If necessary, treatment to prevent complications of nephrotic syndrome is associated with it. To reduce swelling, a salt-free diet, regular albumin infusions and diuretics are prescribed. Treatments to reduce proteinuria and protect the kidney, anticoagulants to limit the risk of thrombosis, treatments to reduce cholesterol and triglyceride levels and/or synthetic thyroid hormones and/or synthetic growth hormone are also prescribed. Nevertheless, progression to end-stage renal disease is frequent and requires dialysis and/or a kidney transplant. In this case, there is a risk of recurrence of nephrotic syndrome after kidney transplantation.

Which organs are affected?

Apart from edemas, often unsightly but usually without severe consequences, nephrotic syndrome exposes to certain complications.

  • Infections : Bacterial infections are common and can occur early in the course of the disease. They may include peritonitis (infection of the peritoneum) causing severe abdominal pain and fever, meningitis, pneumonia or cellulitis (infection of the subcutaneous tissues). All of these infections can be controlled with antibiotics. Viral infections may be promoted by the treatment given to treat nephrotic syndrome such as prednisone or immunosuppressants. This is particularly the case with chickenpox, which can be serious. There are effective medications that should be given if chickenpox develops to avoid complications of the disease, and if contact is made with a person who has chickenpox to prevent its onset.
  • Thrombosis: Nephrotic syndrome is responsible for coagulation abnormalities that increase the risk of blood clots forming in the circulation. These are thrombosis events that can be localized in the veins of the upper or lower limbs, renal veins, cerebral vessels, pulmonary arteries. The clots can move and cause a pulmonary embolism. These accidents can be prevented by taking medication called anticoagulants.
  • Other complications : When treatments are not effective and do not lead to remission, urinary leakage of protein can be responsible, in the long term, for a state of malnutrition with muscle wasting, Height growth disorder, disturbances in lipid profile and thyroid insufficiency. Sclerosis lesions may appear and progress in the kidneys, leading to chronic kidney failure within an unspecified period of time, which may be several years.
    Certain very rare genetic forms are associated with damage to other organs (heart, eye, nervous system, etc.).

How is steroid resistant nephrotic syndrome monitored?

In addition to regular monitoring of proteinuria and blood albumin levels, growth, kidney function (urea and blood and urinary creatinine), and immunosuppressive drug dosages are monitored regularly.

Membranous glomerulonephritis

What is membranous glomerulonephritis?

The kidneys contain glomeruli that filter the blood, functioning like sieves, retaining large substances (proteins and blood cells) and letting through waste products, small substances mainly from food, such as water, salt, urea. These filtered wastes are then found in the urine.

Schema glomérulonéphrite extramembraneuseA nephrotic syndrome occurs when the holes in the sieve widen, allowing proteins (proteinuria), mainly albumin, to pass into the urine (albuminuria). The result is a decrease in the concentration of albumin in the blood, which normally ensures the maintenance of water and salt in the blood through a « sponge » effect. The water and salt will therefore pass from the bloodstream into the tissues and cause edemas.

Membranous glomerulonephritis (MGN) is the most common cause of nephrotic syndrome in adults over the age of 50. It is characterized by granular deposits of antibodies on the outer side of the filter on kidney biopsy, which explains the term « membranous ».

How common is membranous glomerulonephritis?

The exact number of new cases annually in the general population remains poorly known. It is estimated at 1.3 per 100,000 adults. It is therefore a rare disease.

What is the evolution of membranous glomerulonephritis?

The evolution is highly variable from one patient to another: approximately one third of patients go into spontaneous remission, one third remain with variable proteinuria and may have some degree of renal failure, and one third progress to severe chronic renal failure requiring dialysis or transplantation. The disease can recur on the graft after kidney transplantation in almost 50% of cases and eventually compromise its function.

What causes membranous glomerulonephritis?

MGN is sometimes associated with another disease such as cancer, infections, especially viral (hepatitis B) or parasitic infections, or the use of certain drugs. Most often, it occurs without any other apparent disease, justifying until recently the term idiopathic.

glomérulonéphrite extramembraneuse anglaisMGN is an autoimmune disease, characterized by the production of antibodies directed against our own antigens located in the glomerular filters.

The Parisian team at the Tenon Hospital was the first to identify such an antigen in newborn children (1), and contributed with the Nice team to identify antigens in adults using different techniques, based on genetics or biochemistry. These antigens have code names whose meaning is of little importance, whether they are NEP in children or adults, PLA2R1 in about 80% of cases (2), or THSD7A (3) in less than 5% of cases. Thus, there are still other antigens to be discovered.

Our immune system normally produces antibodies to protect us against the various pathogens in our environment (bacteria, viruses, parasites…). For as yet unknown reasons, within the framework of GEMs, our organism produces antibodies against proteins (PLA2R1, THSD7A) which form the meshes of this sieve.

There are also cases in children that are due to the production of antibodies against food antigens such as beef albumin brought by meat or milk (4), which brings to mind the increasingly important role of the environment, including pollution.

What are the symptoms of membranous glomerulonephritis?

A nephrotic syndrome is suspected when there are edemas, responsible for puffiness of the eyelids in the morning and swelling of the ankles during the day. Excess water and salt in the body can also cause an effusion in the envelope (pleura) surrounding the lungs (pleural effusion), and more rarely a swelling of the abdomen (ascites) or the bursae in men (hydrocoele). These edemas are bothersome, but most often, they are not dangerous.

They can be easily linked to nephrotic syndrome by testing for proteins in the urine using a simple test strip.

Sometimes there are no symptoms and the diagnosis is made incidentally during a blood or urine test that reveals proteinuria.

Finally, the disease can be revealed by various complications: abdominal pain, shortness of breath, infection, headaches, clots in the circulation (thrombosis) that can move and rarely lead to a pulmonary embolism.

What tests are required for diagnosis?

When the diagnosis is suspected, we look for proteins in the urine. The simplest way to do this is to use strips, such as Albustix®, which are dipped into the urine and then compared in color with those on the vial. The color of the strip will change from yellow when there is no proteinuria to light or dark green depending on the degree of proteinuria. It can then be determined whether the proteinuria test is negative or positive, with a scale of one, two, three or four crosses. The presence of « traces » should not be a cause for concern.

When the protein test strip is positive, it is important to specify the amount of protein lost in the urine. This can be done in the laboratory on a morning sample or on a 12-hour or 24-hour urine collection.

The diagnosis is then confirmed by a blood test, looking in particular for antibodies specific to the disease (anti-PLA2R1 and anti-THSD7A in adults). A kidney biopsy remains desirable in most patients because it provides additional diagnostic information.

What are the treatments to follow?

The treatment has two goals :

  • Symptomatic, i.e. it addresses the symptoms (decrease proteinuria and edemas) and aims to prevent complications of the disease,
  • Curative, healing the patient, preventing the production of antibodies.

Since one third of patients go into remission spontaneously, treatment is often initially symptomatic for 6 months in the absence of signs of severity (progressive renal failure or serious complications of nephrotic syndrome). A treatment that blocks the renin-angiotensin-aldosterone system (conversion enzyme inhibitor or angiotensin II receptor blocker) can reduce proteinuria at the cost of lower blood pressure. It is combined with a salt-free diet and diuretics to reduce edemas. In some cases (very low albumin levels in the blood), anticoagulants to limit the risk of thrombosis and cholesterol-lowering treatments (statins) are also proposed.

The curative treatment of MGN remains controversial. It is based on the use of immunosuppressive drugs (drugs that lower the immune system’s defenses to decrease the production of antibodies). Corticosteroids alone are generally ineffective, and do not achieve complete remission, i.e. making the filter impermeable to proteins again and making proteinuria disappear.

Immunosuppressive therapy is recommended in cases of deterioration of renal function or nephrotic syndrome persisting 6 months after initiation of symptomatic treatment. However, this delay may induce irreversible damage. Until recently, no marker could predict the evolution of a patient. The discovery of anti-PLA2R1 and anti-THSD7A antibodies has led to the identification of new markers predictive of the evolution of renal function. A high level of anti-PLA2R1 antibodies at diagnosis appears to be associated with a lower chance of remission. More important than a high level of antibodies at diagnosis is their persistence in the weeks or months following diagnosis (5).  Anti-PLA2R1 antibodies are directed against at least 3 different domains of PLA2R1. It appears that patients immunized against a single PLA2R1 domain go into spontaneous remission more often, whereas patients immunized against multiple PLA2R1 domains appear to have an unfavorable course in the absence of curative treatment with a higher risk of adverse disease progression (6,7).  Antibody assays and perhaps analysis of their specificity with respect to the mentioned domains should allow us to propose a more personalized care.

Image 3 Glomérulonéphrite extramembraneuseNevertheless, progression to severe renal failure is possible, requiring then dialysis and/or a kidney transplant. In this case, there is a risk of MGN recurrence after kidney transplantation (8,9).

How is membranous glomerulonephritis monitored?

In addition to regular monitoring of proteinuria and blood albumin levels, kidney function (urea and blood creatinine), and anti-PLA2R1 (or more rarely anti-THSD7A) antibody levels are monitored regularly. Measurement of PLA2R1 antibody levels is available in most hospital centers in France. The Nice and Paris-Tenon centers can also perform serum anti-THSD7A antibody testing.

The Nice center has developed techniques for assaying antibodies directed against certain areas of the molecule (epitopes), which for the moment are research techniques, and whose usefulness in the clinic must be validated and demonstrated to be superior to that of simple antibody assays.

Bibliographical references

1. Debiec H, Guigonis V, Mougenot B, Decobert F, Haymann JP, Bensman A, et al. Antenatal membranous glomerulonephritis due to anti-neutral endopeptidase antibodies. N Engl J Med. 2002;346(26):2053-60.

2. Beck LH, Jr., Bonegio RG, Lambeau G, Beck DM, Powell DW, Cummins TD, et al. M-type phospholipase A2 receptor as target antigen in idiopathic membranous nephropathy. N Engl J Med. 2009;361(1):11-21.

3. Tomas NM, Beck LH, Jr., Meyer-Schwesinger C, Seitz-Polski B, Ma H, Zahner G, et al. Thrombospondin type-1 domain-containing 7A in idiopathic membranous nephropathy. N Engl J Med. 2014;371(24):2277-87.

4. Debiec H, Lefeu F, Kemper MJ, Niaudet P, Deschenes G, Remuzzi G, et al. Early-childhood membranous nephropathy due to cationic bovine serum albumin. N Engl J Med. 2011;364(22):2101-10.

5. Dahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, Michel PA, Mihout F, Dussol B, Matignon M, Mousson C, Simon T, Ronco P; GEMRITUX Study Group. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up. J Am Soc Nephrol. 2017 Jan;28(1):348-358.

6. Seitz-Polski B, Dolla G, Payre C, Girard CA, Polidori J, Zorzi K, et al. Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy. J Am Soc Nephrol. 2016;27(5):1517-33.

7. Seitz-Polski B, Debiec H, Rousseau A, Dahan K, Zaghrini C, Payré C, Esnault VLM, Lambeau G, Ronco P. Phospholipase A2 Receptor 1 Epitope Spreading at Baseline Predicts Reduced Likelihood of Remission of Membranous Nephropathy. J Am Soc Nephrol. 2017 Nov 7. pii: ASN.2017070734. doi: 10.1681/ASN.2017070734.

8. Debiec H, Martin L, Jouanneau C, Dautin G, Mesnard L, Rondeau E, et al. Autoantibodies specific for the phospholipase A2 receptor in recurrent and De Novo membranous nephropathy. Am J Transplant. 2011;11(10):2144-52.

9. Seitz-Polski B, Payre C, Ambrosetti D, Albano L, Cassuto-Viguier E, Berguignat M, et al. Prediction of membranous nephropathy recurrence after transplantation by monitoring of anti-PLA2R1 (M-type phospholipase A2 receptor) autoantibodies: a case series of 15 patients. Nephrol Dial Transplant. 2014;29(12):2334-42.

Other pathologies

  • Post-transplant recurrence of idiopathic nephrotic syndrome
  • Idiopathic nephrotic syndrome with minimal steroid sensitive glomerular lesions in adults
En savoir +

Pediatric nephrology

Pr Olivia Gillion Boyer, néphrologue pédiatre

Pediatric nephrologist
Pr Olivia Gillion-Boyer

MD, PhD

Laurence Heidet

Pediatric nephrologist
Dr Laurence Heidet

MD, PhD

Marina charbit MAT

Pediatric nephrologist
Dr Marina Charbit

MD, PhD

Pr remi Salomon

Pediatric nephrologist
Pr Rémi Salomon
MD, PhD

Nathalie Biebuyck-Gouge

Pediatric nephologist
Dr Nathalie Biebuyck-Gouge
MD

Laurene Dehoux MAT

Pediatric nephrologist
Dr Laurène Dehoux
MD

Adult nephrology

Pr Knebelmann

Adult nephrologist
Pr Bertrand Knebelmann
MD, PhD

Aude Servais Service Néphrologie Hôpital Necker à Paris.Avril 2016

Adult nephrologist
Dr Aude Servais

MD, PhD

photo-identite-femme magec2

Adult nephrologist
Dr Myriam Dao
MD

photo-identite-femme magec2

Adult nephrologist
Dr Aurélie Hummel
MD

Research

Research for new genes involved in hereditary nephrotic syndromes

Research of new therapeutic strategies in hereditary nephrotic syndromes

  • LYMPHOSNIT : Biomarker Research in Idiopathic Nephrotic Syndrome ANSM Association Funding
  • GLUCOPED : Study of corticosteroid pharmacokinetics in children (NCT02252237)
  • NEPHROVIR-3: Randomized trial investigating the value of elmisole in the first relapse of steroid-sensitive idiopathic nephrotic syndrome
  • NEPHRITUX STUDY ORPHA276778: A prospective randomised double blind placebo-controlled phase II/II study evaluating the efficacy of Rituximab in the prevention of relapse of calcineurin dependent idiopathic nephrotic syndrome of childhood-FR (National study)
  • RITUXIVIG : Efficacy and safety of immunoglobulin associated with Rituximab versus Rituximab alone in childhood-onset steroid-dependent nephrotic syndrome (RITUXIVIG)
  • RIFIREINS : Rituximab from the first episode of minimal change nephrotic syndrome for preventing relapse risk in adult patients: a multicenter randomized controlled trial
  • INS Biobank: From immune system damage to podocyte cell damage: prospective database and biological collection of patients (children and adults) suffering from minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS).
  • PMNN: « Customized care of membranous glomerulonephritis » – PMMN

Education

IUD Pediatric nephrology
Paris university 

Logo Université de Paris

Pediatric nephrology

1. Dorval G, Gribouval O, Martinez-Barquero V, Machuca E, Tête MJ, Baudouin V, Ronco P, Rondeau E, Sallee M, Tsimaratos M, Ulinski T, Salomon R, Antignac C, Boyer O. Clinical and genetic heterogeneity in familial steroid-sensitive nephrotic syndrome. Pediatr Nephrol. 2017 Oct 23. doi:10.1007/s00467-017-3819-9. [Epub ahead of print] PubMed PMID: 29058154.

2. Gruppen MP, Bouts AH, Jansen-van der Weide MC, (…) Niaudet P, Cornelissen EAM, Schurmans T, Raes A, van de Walle J, van Dyck M, Gulati A, Bagga A, Davin JC; all members of the Levamisole Study Group. A randomized clinical trial indicates that levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome. Kidney Int. 2017 Oct 17. pii: S0085-2538(17)30607-5. doi:10.1016/j.kint.2017.08.011. [Epub ahead of print] PubMed PMID: 29054532.

3. Boyer O, Dorval G, Servais A. Hereditary Podocytopathies in Adults: The Next Generation. Kidney Dis (Basel). 2017 Jul;3(2):50-56. doi: 10.1159/000477243. Epub 2017 May 31. Review. PubMed PMID: 28868292; PubMed Central PMCID: PMC5566765.

4. Dossier C, Lapidus N, Bayer F, Sellier-Leclerc AL, Boyer O, de Pontual L, May A, Nathanson S, Orzechowski C, Simon T, Carrat F, Deschênes G. Epidemiology of idiopathic nephrotic syndrome in children: endemic or epidemic? Pediatr Nephrol. 2016 Dec;31(12):2299-2308. Epub 2016 Oct 24. PubMed PMID:27778092.

> More publications

Adult nephrology

1. Kormann R, Jannot AS, Narjoz C, Ribeil JA, Manceau S, Delville M, Joste V, Prié D, Pouchot J, Thervet E, Courbebaisse M, Arlet JB. Roles of APOL1 G1 and G2 variants in sickle cell disease patients: kidney is the main target. Br J Haematol. 2017 Oct;179(2):323-335.

2. Garrouste C, Canaud G, Büchler M, Rivalan J, Colosio C, Martinez F, Aniort J, Dudreuilh C, Pereira B, Caillard S, Philipponnet C, Anglicheau D, Heng AE.
Rituximab for Recurrence of Primary Focal Segmental Glomerulosclerosis After Kidney Transplantation: Clinical Outcomes. Transplantation. 2017 Mar;101(3):649-656.

3. Dahan K, Debiec H, Plaisier E, Cachanado M, Rousseau A, Wakselman L, Michel PA, Mihout F, Dussol B, Matignon M, Mousson C, Simon T, Ronco P; GEMRITUX Study Group.. Rituximab for Severe Membranous Nephropathy: A 6-Month Trial with Extended Follow-Up. J Am Soc Nephrol. 2017 Jan;28(1):348-358

4. Baye E, Gallazzini M, Delville M, Legendre C, Terzi F, Canaud G. The costimulatory receptor B7-1 is not induced in injured podocytes. Kidney Int. 2016
Nov;90(5):1037-1044

5. Delville M, Baye E, Durrbach A, Audard V, Kofman T, Braun L, Olagne J, Nguyen C, Deschênes G, Moulin B, Delahousse M, Kesler-Roussey G, Beaudreuil S, Martinez F, Rabant M, Grimbert P, Gallazzini M, Terzi F, Legendre C, Canaud G. B7-1 Blockade Does Not Improve Post-Transplant Nephrotic Syndrome Caused by Recurrent FSGS. J Am Soc Nephrol. 2016 Aug;27(8):2520-7.

 > More publications

Corticotherapy
Corticosteroid treatment in the form of prednisone or prednisolone for example. Corticosteroids are normally produced by the body and regulate many functions. Corticosteroids can also be given as medication because they decrease inflammation and certain immune system responses.

Diuretics
Drugs that increase the elimination of salt in the urine and consequently increase the volume of urine.

Edema
Swelling related to an excess of water and salt, often localized at the ankles or eyelids.

Idiopathic
Whose cause and mechanism is unknown.

Kidney biopsy or needle kidney biopsy 
Removal of a small kidney fragment for microscopic examination.

Minimal glomerular lesions
The kidney appears normal under the microscope. This is the most common case during steroid-sensitive nephrotic syndrome.

Nephrotic syndrome
Presence of significant amounts of protein in the urine associated with a decrease in the level of albumin in the blood.

Peritonitis
Bacterial infection of the peritoneum, the membrane that surrounds the organs in the abdomen.

Remission
Disappearance of proteinuria.

Segmental or focal hyalinosis
The kidney appears under the microscope with small areas of fibrosis.

Thrombosis
Formation of a clot in a vessel whether a vein or an artery. This clot can move in a vein and migrate into the lung, causing a pulmonary embolism.

Contact information

Necker-Enfants malades university hospital
> Nephrology department

149 rue de Sèvres
75743 PARIS Cedex 15

> Welcome booklet – Adult patients

> Pediatric welcome booklet

In Necker, the reference center for idiopathic nephrotic syndrome in brief 

0
patients followed at least once a year*
0
medical consultations*
0
day hospitalizations*
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patients in full hospitalization*
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ongoing research projects*
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university courses*
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publications*

* data valid for 2020