Nephronophthisis

Medical quality assurance by Dr. Albrecht Nonnenmacher, MD at December 16, 2016
StartDiseasesNephronophthisis

Nephronophthisis is an inherited kidney disease. It means “the wasting of nephrons,” which are structures in the kidneys that regulate water and electrolytes. It is caused when a child inherits a mutated gene from the mother and the father in an autosomal recessive inheritance pattern. The parents, who are genetic carriers, usually don’t have signs or symptoms of the disease. 

Contents

Definition & Facts

Nephronophthisis is a condition where the kidneys are damaged by scarring or fibrosis that accumulates to the point where the kidneys can no longer do their job of removing waste from the body. An area in the kidneys called the corticomedullary region is also invaded by fluid-filled cysts.

Nearly all cases of nephronophthisis do not have symptoms that involve organs other than their kidneys, though in some cases patients suffer fibrosis of the liver, heart defects, or situs inversus - a condition where at least one internal organ is on the opposite side of the body where it is normally found.

There are other syndromes of which nephronophthisis is a part, including Joubert syndrome, Senior-Løken syndrome, Bardet-Biedl syndrome, Meckel-Gruber syndrome, COACH syndrome, and Leber congenital amaurosis. In addition to suffering from nephronophthisis, a patient with one of these disorders may also have too many fingers or toes and suffer eye problems, intellectual disabilities, and problems with the skeletal system.

There are three main subtypes of nephronophthisis. They are infantile, juvenile and adolescent. These stages of life describe the age at which the patient’s kidneys begin to fail.

Infantile nephronophthisis can be detected in the womb, and the patient begins to experience kidney failure when they are about a year old. When they are born, their lungs can be smaller than usual, their limbs may be contracted, and they may have facial deformities. In juvenile nephronophthisis, the kidneys start to fail when the patient’s about 13. In the adolescent type, the kidneys fail when they are about 19. Juvenile is the most common type of nephronophthisis. 

Nephronophthisis invariably leads to end-stage renal disease and is its most common genetic cause among young people. Its occurrence differs in different parts of the world. For example, it affects 1 in 50,000 births in Canada and 1 in 922,000 births in the United States. Nephronophthisis occurs equally in boys and girls.

Symptoms & Complaints

People who have nephronophthisis often suffer from:

Causes

The causes of nephronophthisis are genetic, but they are complex. There are several kinds of genetic mutations that can result in the disease. In nephronophthisis type 1, there’s mutation on the NPHP1 gene which makes proteins that affect cilia. Cilia transmit chemical signals and resemble a type of fringe on kidney cells and other types of cells. The mutated genes disrupt the cilia’s ability to send chemical signals, which impairs the functioning of the kidneys.

Other NPH genes, some of which haven’t been identified by scientists, the CEP164 gene, the TTC21B gene, and the ANKS6 gene also have roles in the proper functioning of cilia, and mutations in all of them are implicated in nephronophthisis.

Diagnosis & Tests

Doctors can find nephronophthisis during an ultrasound examination of the patient’s kidneys. They also take a medical history and family history of the patient. Some doctors find it best to have knowledge of at least three generations of the family of a patient with nephronophthisis.

Treatment & Therapy

The treatment of nephronophthisis involves easing the patient’s symptoms. Their electrolytes and water intake need to be balanced, and their anemia needs be treated. Children whose growth has been stunted because of their nephronophthisis can be given growth hormones. When the end-stage renal disease develops, the patient must be placed on dialysis to cleanse their blood of toxins or undergo a kidney transplant to save their life.

Complications that are secondary to the disease such as flu need to be avoided. The doctor will recommend that the patient have annual flu vaccines, pneumococcal vaccines, and hepatitis B vaccines. These vaccines lower the patients' risk of developing cardiovascular disease.

It is important that the patient be monitored fairly closely. Their blood pressure, kidney function, and liver function need to be checked at least once a year. The doctor also checks to see how the child is developing both physically and psychologically. Clinical urine tests can tell whether protein is present in the urine (proteinuria), and an abdominal ultrasound can tell whether there are complications in other organs, including the biliary organs. The child’s eyes need to be checked to make sure that their eyes are healthy. Some nephronophthisis patients are at risk for deterioration of their retinas.

Patients with nephronophthisis are told to avoid NSAIDs, or nonsteroidal anti-inflammatory drugs such as ibuprofen. They are also told to avoid antibiotic drugs called aminoglycosides, and imaging studies that require them to take a contrast agent such as iodine or barium.

Prevention & Prophylaxis

Though nephronophthisis cannot be prevented, it is possible to evaluate relatives of the patient who may be at risk for the disease before they start showing any symptoms. The siblings of a person who has nephronophthisis has a 25 percent chance of getting the disease, and a 50 percent chance of being a carrier. The earlier the disease is found and diagnosed, the more successfully it can be treated. This course of action is especially helpful since in most cases the disease takes many years to progress.

Genetic testing can also be done for patients and people who suspect that they might be carrying a damaged NPHP gene. Prenatal testing can also be done.