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-congenital nephrotic syndrome (start/mid). Articles needs additional citations for verification. Might also benefit from inclusion of genetic diseases

-sarcoidosis (B/mid). Might benefit from expansion of renal involvement

-hypercalciuria (stub/mid)

'''I am currently working on the article "Congenital Nephrotic Syndrome". I have indicated below what is currently there and how I am planning to improve. Much of this information needs to be updated to reflect our current knowledge'''

= Congenital Nephrotic Syndrome = Prior: Congenital nephrotic syndrome is an inherited disorder characterized by protein in the urine and swelling of the body.

Change: Congenital nephrotic syndrome is a rare kidney disease which manifests in infants during the first 3 months of life, and is characterized by high levels of protein in the urine (proteinuria), low levels of protein in the blood, and swelling. This disease is primarily caused by genetic mutations which result in damage to components of the glomerular filtration barrier and allow for leakage of plasma proteins into the urinary space.

Symptoms
Prior:


 * Low birth weight
 * Large placenta
 * Swelling (total body)
 * Decreased urine output
 * Foamy appearance of urine
 * Poor appetite
 * Cough

Complications

 * Frequent, severe infections
 * Malnutrition and related diseases
 * Blood clots
 * Acute kidney failure
 * Chronic kidney failure
 * End-stage kidney disease

Change:

Urine protein loss leads to total body swelling (generalized edema) and abdominal distension in the first several weeks to months of life. Fluid retention may lead to cough (from pulmonary edema), ascities, and widened cranial sutures and fontanelles. High urine protein loss can lead to foamy urine. Infants may be born prematurely with low birth weight, and have meconium stained amniotic fluid or a large placenta.

Complications

 * Frequent, severe infections: urinary loss of immunoglobulins
 * Malnutrition and poor growth
 * Blood clots (hypercoagulability): imbalance of plasma coagulation factors from urine protein loss
 * Hypothyroidism: urinary loss of thyroid-binding protein
 * Poor bone health associated with vitamin D deficiency: urinary loss of vitamin D binding protein
 * Acute kidney injury
 * Chronic kidney disease and ultimately end-stage kidney disease

Causes
Prior:

Congenital nephrotic syndrome is a very rare form of nephrotic syndrome. It occurs predominantly in families of Finnish origin and manifests shortly after birth. It is an inherited disorder. The condition is caused by a defect in the protein nephrin, which is found in the kidney.

Proteins and fats are excreted in the urine, and there is an abnormally high fat level in the blood. Swelling occurs due to kidney failure, combined with the loss of blood protein. This is because proteins in the blood normally keep fluids in the blood stream, and when protein level is low, the fluid can leak into the body tissues.

Some of the proteins lost in the urine are immune system antibodies that fight infections. The disorder commonly results in infection, malnutrition, and kidney failure.

Change:

Primary (Genetic) Causes:
Mutations in the following five genes account for greater than 80% of the genetic causes of congenital nephrotic syndrome:


 * NPHS1 (Finnish Type): The gene NPHS1 encodes for the protein nephrin. This genetic variant is characterized by severe protein loss in the first days to weeks of life. Fin-major and Fin-minor were the first two main genetic mutations identified in Finnish newborns, however, numerous mutations have now been identified in patients all over the world from various ethnic groups. It is the most common cause of primary congenital nephrotic syndrome, accounting for 40-80% of cases.
 * NPHS2: This gene encodes for the protein podocin. Patients with this genetic mutation develop nephrotic syndrome in the first few weeks of infancy, but can also manifest symptoms later in life. Urinary protein loss is less severe when compared with the Finnish type. Both nephrin and podocin play important roles in the structure and function of the podocyte filtration slit diaphragm and disease involvement is typically limited to the kidneys
 * WT1: The Wilms' tumor suppressor gene regulates the expression of many genes involved in kidney and urogenital development. Mutations lead to several types of developmental syndromes, including Denys-Drash syndrome, Frasier syndrome, WAGR syndrome (Wilm's tumor, aniridia, genitourinary abnormalities, and mental retardation), and isolated nephrotic syndrome in infants. Depending on the specific syndrome, patients are at risk for Wilms' and other tumors, genital abnormalities, and nephrotic syndrome.
 * LAMβ2 (Pierson syndrome): This gene encodes for the protein laminin β2, which helps attach podocytes to the glomerular basement membrane. Patients with Pierson syndrome have eye abnormalities, including nonreactive narrowing of the pupils (microcoria), and neurologic deficits.
 * PLCε1: Codes for the enzyme Phospholipase Cε1, which is expressed in podocytes.

Secondary Causes:

 * Congenital infections: syphilis, cytomegalovirus, toxoplasmosis, rubella, human immunodeficiency virus (HIV), malaria, hepatitis B
 * Immunologic: maternal systemic lupus erythematosus

Diagnosis
Prior:

An examination reveals massive fluid retention and generalized swelling. Abnormal sounds are heard when listening to the heart and lungs with a stethoscope. Blood pressure may be high. The patient may have signs of malnutrition.

A urinalysis reveals large amounts of protein and the presence of fat in the urine. Total protein in the blood may be low. The disorder can be screened during pregnancy by finding elevated levels of alpha-fetoprotein on a routine sampling of amniotic fluid. Genetic tests should be used to confirm the diagnosis, if the screening test is positive.

CNF is one of the Finnish heritage diseases. By use of positional cloning strategies, Kestila et al. isolated the gene responsible for NPHS1. Mutations in Finnish patients with NPHS1 were found in this gene, which they termed nephrin. The most common Finnish mutation was a deletion of 2 nucleotides in exon 2 (602716.0001), resulting in a frameshift and a truncated protein. The predicted nephrin protein belongs to the immunoglobulin family of cell adhesion molecules and is specifically expressed in renal glomeruli. It was also observed that, in most cases, alleles typically found on CNF chromosomes of Finnish families were also found on CNF chromosomes of non-Finnish families from North America and Europe.

Frequent infections may occur over the course of the disease.

Change:

An examination reveals massive fluid retention and generalized swelling. Abnormal sounds are heard when listening to the heart and lungs with a stethoscope. Blood pressure may be high. The patient may have signs of malnutrition.

A urinalysis reveals large amounts of protein and sometimes small amounts of blood. Kidney function may be normal in the first weeks or months of life. Laboratory studies show low levels of protein (albumin) and immunoglobulins in the blood, and elevated levels of triglycerides and cholesterol. Blood work may also show thyroid and vitamin D deficiency. Kidneys on ultrasound may be enlarged and hyperechoic. The disorder can be screened during pregnancy by finding elevated levels of alpha-fetoprotein on a routine sampling of amniotic fluid.

Indication for kidney biopsy remains unclear as histologic findings do no reveal the cause of congenital nephrotic syndrome, but findings may help in developing treatment strategies. Findings on light microscopy can vary from minimal change nephropathy to focal segmental glomerulosclerosis or diffuse mesanigal sclerosis. Electron microscopy shows podocyte disruption (loss of foot processes or slit diaphragm).

Genetic analysis and infectious workup are needed to determine the precise cause of congenital nephrotic syndrome. Understanding the underlying cause can assist in disease management, prognosis, and genetic counseling.

Treatment
Prior:

Early and aggressive treatment is required to control the disorder. Diuretic medications help rid the body of excess fluid. ACE inhibitor medications (like Captopril and others) and non-steroidal anti-inflammatory drugs (like indomethacin) are used to slow the spilling of protein (albumin) in the urine. Antibiotics may be needed to control infections. Patients may also take iron supplements, potassium chloride, thyroxine and other vitamins to replenish what minerals the kidneys have leaked out.

Most patients will undergo regular and frequent albumin infusion (often daily) to replace what kidneys have lost. Infusions are performed via IV so a central venous catheter will need to be surgically inserted into patients chest or groin.

Dietary modifications may include the restriction of sodium and use of dietary supplements as appropriate for the nature and extent of malnutrition. Fluids may be restricted to help control swelling.

Many patients have a gastrostomy tube (g-tube) inserted for medication and/or feeds. Some patients develop oral aversions and will use the tube for all feeds. Other patients eat well and only use the tube for medicine or supplemental feeds. The tube is also useful for patients needing to drink large amounts of fluids around the time of transplant.

Patient will require removal of the kidneys (one at the time or both), dialysis, and ultimately a kidney transplant.

Change:

Genetic forms of nephrotic syndrome are typically resistant to steroid and other immunosuppressive treatment. Goals of therapy are to control urinary protein loss and swelling, provide good nutrition to allow the child to grow, and prevent complications. Early and aggressive treatment is required to control the disorder.

Patients with severe urine protein loss require albumin infusions help replace protein loss and diuretic medications help rid the body of excess fluid. For patients with mild to moderate urine protein losses, ACE inhibitor medications (like Captopril and others) and non-steroidal anti-inflammatory drugs (like indomethacin) are used to slow the spilling of protein (albumin) in the urine. Removal of the kidneys (one at the time or both) can decrease protein loss and limit the number of albumin infusions needed. Infants with WT1 mutations will undergo bilateral kidney removal to prevent development of Wilms' tumor.

Antibiotics may be needed to control infections. Immunizations are recommended after kidney removal but prior to transplantation. Patients may also take iron supplements, potassium chloride, thyroxine and other vitamins to replenish what minerals the kidneys have leaked out. Anticoagulants (such as aspirin, dipyridamole, and warfarin) are used to prevent clot formation.

Dietary modifications may include the restriction of sodium and use of dietary supplements as appropriate for the nature and extent of malnutrition. Fluids may be restricted to help control swelling. Children with this disease require diets with high amounts of calories and protein, and many patients require a feeding tube (nasogastric tube or gastrostomy tube (g-tube)) for medication and/or feeds. Some patients develop oral aversions and will use the tube for all feeds. Other patients eat well and only use the tube for medicine or supplemental feeds. The tube is also useful for patients needing to drink large amounts of fluids around the time of transplant.

While infants with infectious causes of congenital nephrotic syndrome may be cured with antibiotics or antiviral medications, those with genetic causes progress to end-stage renal disease and require dialysis and/or kidney transplantation.

Prognosis
Prior:

Congenital nephrotic syndrome can be successfully controlled with early diagnosis and aggressive treatment including albumin infusions, nephrectomy, medications and ultimately a kidney transplant. Most children live fairly normal life post-transplant but will spend significant time hospitalised pre-transplant and have numerous surgeries to facilitate treatment.

Due to the protein (albumin) losses many patients have reduced muscle tone and may experience delays in certain physical milestones such as sitting, crawling and walking. Similarly many patients experience growth delays due to protein loss. Delays vary from mild to significant but most patients experience growth spurts once they receive their transplanted kidney. Physical therapy may be useful for the child to strengthen muscle tone.

Undiagnosed cases are often fatal in the first year due to blood clots, infections or other complications.

Change:

Congenital nephrotic syndrome can be successfully controlled with early diagnosis and aggressive treatment including albumin infusions, nephrectomy, and medications. Affected children have rapid decline in kidney function resulting in end-stage renal disease within the first years of life, and require treatment with dialysis and kidney transplantation. Most children live fairly normal life post-transplant but will spend significant time hospitalised pre-transplant and have numerous surgeries to facilitate treatment. Kidney transplantation outcomes for children with congenital nephrotic syndrome are similar to those of other patient groups. Nephrotic syndrome typically does not reoccur following kidney transplantation, however recurrences have been seen in children with NPHS1 mutations who develop anti-nephrin antibodies.

Due to the protein (albumin) losses many patients have reduced muscle tone and may experience delays in certain physical milestones such as sitting, crawling and walking. Similarly many patients experience growth delays due to protein loss. Delays vary from mild to significant but most patients experience growth spurts once they receive their transplanted kidney. Physical therapy may be useful for the child to strengthen muscle tone. Children who have a history of stroke from blood clots can have neurologic complications.

Undiagnosed cases are often fatal in the first year due to blood clots, infections or other complications.