What are the other Names for this Condition? (Also known as/Synonyms)

• NPH (Nephronophthisis)
• NPHP (Nephronophthisis)

What is Nephronophthisis? (Definition/Background Information)

• Nephronophthisis (NPH or NPHP) is a group of rare genetic disorder that consists of a variety of kidney abnormalities including corticomedullary cyst, atrophy of kidney, and interstitial fibrosis. Nephronophthisis is described as a type of medullary cystic kidney disease (MCKD)
• The condition is bilateral (affecting both kidneys) and progressive in nature. 3 forms of Nephronophthisis, based on the age of onset of end-stage renal disease, are recognized and these include:
  • Infantile Nephronophthisis
  • Juvenile Nephronophthisis
  • Adolescent Nephronophthisis
• A family history of Nephronophthisis increases one’s risk for the disorder. The cause of the disorder is genetic abnormalities involving the NPHP gene that is inherited in an autosomal recessive manner
• Nephronophthisis presents with signs and symptoms that include high blood pressure, anemia, skeletal abnormalities, increased thirst and urination, and reduced kidney function that can result in end-stage kidney disease
• There is no cure for the genetic condition, and presently, Nephronophthisis cannot be prevented. The treatment is directed towards managing the symptoms of the condition and includes urinary dialysis and kidney transplantation
• The prognosis of Nephronophthisis is generally guarded and depends on the success of the renal transplant procedure. The prognosis is also based on the form of Nephronophthisis and the severity of the symptoms; typically, infantile forms have the worst outlook

Who gets Nephronophthisis? (Age and Sex Distribution)

• Nephronophthisis is a rare kidney disorder (incidence of 1 in 50,000); the symptoms develop in infancy, childhood, during adolescence or teenage
• It affects both male and female gender and no preference is noted
• All racial and ethnic groups are at risk

What are the Risk Factors for Nephronophthisis? (Predisposing Factors)

• A positive family history of Nephronophthisis increases one’s risk for the condition
• Autosomal recessive condition: If both parents have the gene for Nephronophthisis, then there is a 25% chance that their child will inherit the condition. If only one parent carries the gene, then the child will not develop Nephronophthisis

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Nephronophthisis? (Etiology)

Nephronophthisis is an inherited genetic disorder, and the inheritance pattern is autosomal recessive.

• The NPHP gene is mutated that leads to abnormalities in the cell signaling mechanism
• This genetic defect causes abnormalities in cilia leading to abnormal fetal development and growth
• The disorder is caused by two faulty genes inherited from both the parents. In the autosomal recessive form, parents have no symptoms, but they still carry a recessive gene for the renal condition

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Nephronophthisis?

The signs and symptoms of Nephronophthisis can vary from one individual to another and they may be mild or severe. Also, it depends on the form of Nephronophthisis -  whether infantile, juvenile, or adolescent. The kidney disorder is progressive, and hence, the symptoms are known to get worse with time.

The common signs and symptoms of Nephronophthisis include:

• Abnormally increased urination (polyuria)
• Increased daytime thirst (polydipsia)
• Anemia that results in fatigue, pale skin, and decreased red blood cell count
• High blood pressure (hypertension)
• Fluid and electrolyte imbalances
• Individual may have bone/joint pain due to gout
• Abnormally-formed toes and fingers
• Reduced kidney function
• Both the kidneys are affected

85% of the affected individuals only have abnormalities involving the kidneys and extra-renal symptoms are typically absent.

Signs and symptoms of infantile form of Nephronophthisis may include:

• Kidney may be enlarged due to the presence of multiple cysts
• Other body organs such as the eye, liver, and central nervous system may be affected resulting in the following:
  • Eye involvement due to retinitis pigmentosa resulting in loss of peripheral vision, night blindness, reduced visual acuity, and possible total vision loss
  • Liver involvement: Scarring of liver leading to hepatic fibrosis - this can cause abnormal liver function including jaundice and itching of skin (congenital hepatic fibrosis)
  • Skeletal abnormalities resulting in abnormal bone structures
  • CNS malformation involving the brain and spinal cord, resulting in a variety of symptoms
  • Malrotation of the intestine
  • Situs inversus: Here the location of the abdomen and chest organs is abnormal. Example - the heart is present on the right side, liver on the left side, etc. resulting in related symptoms
• End-stage renal disease by age 1
• Kidney failure by age 3 years -  the signs and symptoms of kidney failure include:
  • Tiredness
  • Swollen face, ankles, feet, or hands (due to water retention)
  • Shortness of breath

Signs and symptoms of juvenile form of Nephronophthisis may include:

• Growth retardation resulting in short stature
• Abnormally-formed bones
• 1 in 10 individuals present retinitis pigmentosa resulting in loss of peripheral vision, night blindness, reduced visual acuity, and possible total vision loss
• In 5-10 years, the individual’s kidney stops functioning resulting in chronic renal failure
• End-stage renal disease by age 13

Signs and symptoms of adolescent form of Nephronophthisis may include:

• Growth retardation resulting in short stature
• Abnormally-formed bones
• Retinitis pigmentosa resulting in loss of peripheral vision, night blindness, reduced visual acuity, and possible total vision loss
• Decreased kidney function resulting in chronic renal failure
• End-stage renal disease by age 19

How is Nephronophthisis Diagnosed?

The diagnosis of Nephronophthisis may involve:

• Complete evaluation of medical history along-with thorough physical exam
• Blood tests including complete blood count (CBC) and metabolic panel
• Testing for fluid and electrolyte imbalances
• Urine analysis
• Abdominal or renal ultrasound: An imaging tool in which sound waves are passed through the body to create images of the kidneys
• Specific diagnostic studies based on the organ involved:
  • Eye examination
  • CT scan of brain
  • Neurological exam with imaging studies of the brain
  • Liver biopsy may show abnormal scarring
• Prenatal testing that includes amniotic fluid analysis and chorionic villi sampling 
• Genetic testing: Confirmation through genetic mutational analysis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Nephronophthisis?

The complications of Nephronophthisis may include:

• Pulmonary edema - fluid accumulation in lungs
• Heart failure
• Gout - bone joint disorder
• Complete loss of vision
• End-stage renal disease (ESRD) - when kidney failure occurs eventually: Nephronophthisis is the most common genetic cause of ESRD in children
• Severe neurological abnormalities

Severe symptoms depending on the specific organ being affected that may include the heart, liver, brain, intestines, etc. may be noted.

How is Nephronophthisis Treated?

Treatment of Nephronophthisis is based on the type and severity of symptoms. It involves the coordinated efforts between a multi-specialty team consisting of pediatricians, surgeons, gastroenterologists, cardiologists, orthopedicians, endocrinologists, and ophthalmologists.

The treatment is focused on decreasing the progression of Nephronophthisis to kidney failure and treating the symptoms. 

• A low-salt and protein-restricted diet is recommended in case of high blood pressure or kidney failure
• Medications, such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), are used to control blood pressure
• Undertaking treatment of anemia
• Correction of vision abnormalities through corrective lenses, although progressive optical atrophy cannot be treated using such lenses
• Growth hormone therapy
• Pain medications for gout
• End-stage renal disease: Patients who progress to end-stage renal disease either require a dialysis (when a machine is used to remove waste products from the body), or a kidney transplantation

How can Nephronophthisis be Prevented?

• Currently, there are no specific methods or guidelines to prevent the Nephronophthisis, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as Nephronophthisis

What is the Prognosis of Nephronophthisis? (Outcomes/Resolutions)

• The prognosis of Nephronophthisis is typically guarded. It depends on the form of Nephronophthisis -  whether infantile, juvenile, or adolescent, severity of the symptoms, the organs involved, and overall health status of the individual
• It is also contingent upon the success of renal transplant. The prognosis may be good in cases where renal transplantation procedure is successful

Additional and Relevant Useful Information for Nephronophthisis:

• Nephronophthisis can occur as part of other syndromes, which are together called Nephronophthisis-associated ciliopathies
• Kidney transplantation is a surgical procedure to remove a damaged or diseased kidney and replace it with a healthy kidney, from a compatible donor

The following article link will help you understand kidney transplantation:

http://www.dovemed.com/common-procedures/procedures-surgical/kidney-transplantation/