Nephronophthisis is a kidney disease that results from a genetic mutation or deletion. Terminal kidney failure presents within these seven forms of the disease by the age of 25 at the latest. To date, the only curative therapy available is transplantation.
What are nephronophthisis?
Nephronophthisis is a genetic kidney disease with chronic inflammatory features. The interstitial renal tissue is the main target of the diseases. To date, seven different inherited diseases have been assigned to this group:
- Juvenile nephronophthisis
- Infantile nephronophthisis
- Adolescent nephronophthisis
The remaining three disorders are referred to as NPHP4, NPHP5, NPHP6, and NPHP7 and have not been well studied. Until the 1970s, researchers described nephronophthisis as medullary cystic kidney disease. Histologically, these diseases can hardly be distinguished from each other. However, the mode of inheritance of medullary cystic kidney disease differs from that of nephronophthisis. Instead of an autosomal dominant mode of inheritance, an autosomal recessive mode of inheritance is present in nephrophthisis. The frequency of all forms is reported to be approximately 1: 100,000.
Causes
The cause of all nephronophthisis is a gene mutation or gene deletion. Thus, the diseases are genetic and are inherited in an autosomal recessive manner. In juvenile nephronophthisis, the mutated gene is located on chromosome 2 gene locus q13. This gene codes for the protein nephrocystin-1. When mutated or deleted, the protein loses its function. Infantile nephronophthisis, on the other hand, is associated with a mutation or deletion on chromosome 9 gene locus q22-q31, which codes for the protein inversin. In the adolescent form, the gene defect is located on chromosome 3 gene locus q21-q22. The fourth form of nephronophthisis is caused by a mutation or deletion on chromosome 1 gene locus p36.22, where the protein nephroretinin is encoded. In the fifth variant, a deletion or mutation is present on chromosome 3 gene locus q21.1, affecting the protein nephrocystin-5. NPHP6 has been attributed to an abnormality on chromosome 12 gene locus q21.33, and in NPHP7, the zinc finger protein is impaired.
Symptoms, complaints, and signs
In all nephronophthisis, enormous salt losses occur, significantly dehydrating the patient and usually causing a shift in electrolyte balance. The urine cannot be brought back to a concentration of 800 mosm*kg-1H2O. Azotemia occurs. Affected individuals thus have an above-average level of nitrogen-containing metabolites in their blood. Anemia or anemia is also among the symptoms of nephronophthisis. In addition, hypokalemia, or potassium deficiency, occurs. Acidosis is equally common. The tubules of the kidneys are atrophic and dilate cytically. Unlike in healthy patients, the tubules are located at the corticomedullary borderline. Cysts form mainly on the collecting tubules of the renal medulla and on the distal convolute of the kidneys. Renal function gradually declines, culminating in terminal renal failure. Only in adolescent nephronophthisis does terminal renal failure occur after the age of majority.
Diagnosis and disease progression
Physicians usually diagnose nephronophthisis using blood tests, urine samples, and renal function scintigraphy, as well as imaging techniques. Imaging options include ultrasound as well as MRI. As a rule, nephronophthisis remains undetected for a long time until severe symptoms develop. The prognosis for affected individuals is rather unfavorable. Terminal renal failure develops in all patients by the age of 25 at the latest. The adolescent form is associated with the comparatively most favorable prognosis, as renal failure in this subtype is not expected until after the age of majority.
Complications
Complications always occur in patients suffering from nephronophthisis. All genetic defects lead to renal failure sooner or later. However, the time of onset of terminal renal failure depends on which genetic defect it is. After that, life can be maintained until a kidney transplant is performed with the help of dialysis.In the most common genetic defect, the NPHP1 defect, terminal kidney failure occurs before the age of 25. It can occur at any time during this period. With the help of symptomatic treatment, the onset of renal failure could still be postponed. The prognosis is even less favorable for the NPHP2 defect. Here, terminal renal failure often occurs before birth, but at the latest within the first year of life. The course of the NPHP3 defect is somewhat more favorable. In this case, terminal kidney failure usually does not occur until around the age of 19. Not much is known about the gene defects NPHP4, NPHP5, NPHP6, NPHP7. However, kidney failure occurs in each case as well. The patient requires constant medical treatment and monitoring, otherwise there is an accumulation of urinary substances in the blood, potassium deficiency, anemia (anemia) and metabolic acidosis (hyperacidity). Despite constant blood purification, total kidney failure can occur, a life-threatening condition that can only be corrected by means of a kidney transplant.
When should you see a doctor?
When to go to the doctor with nephronophthisis depends, among other things, on the nature of the disease and its severity. In general, kidney symptoms should be clarified if they persist for more than a few weeks. Signs of anemia and deficiency symptoms require medical clarification. A doctor must also be consulted in the event of hormonal complaints or kidney pain. Anyone who already suffers from kidney disease should report these complaints to the doctor. Medical advice is also required if an existing disease suddenly becomes more severe or unusual symptoms occur that were not noticed before. The physician will then conduct a comprehensive examination and use this to make a diagnosis. If this is done at an early stage, serious complications can be avoided. For this reason, the first signs must already be clarified and, if necessary, treated. The right contact is the family doctor, an internist or a nephrologist. If the symptoms are severe, the patient should be taken to a hospital immediately. If necessary, a visit to a specialist clinic for kidney disease is also necessary.
Treatment and therapy
There is no causative therapy for patients of nephronophthisis. Treatment is limited to symptom relief. Thus, the piece-by-piece progression of renal failure cannot be halted with current therapeutic options. The only prospect of a complete cure is a kidney transplant. In more than ten percent of all patients, the diagnosis is not made until terminal kidney failure has already occurred. Several treatment options are available as renal replacement therapies after the onset of terminal kidney failure. Dialysis options include hemodialysis and peritoneal dialysis. All dialysis procedures are blood cleansing procedures designed to replace the blood cleansing and detoxifying functions of the kidneys. Hemodialysis is an extracorporeal procedure and thus takes place outside the patient’s own body. Peritoneal dialysis, on the other hand, is an intracorporeal procedure and is used inside the patient’s body. The former procedure is significantly more commonly used as renal replacement therapy. Dialysis cannot replace a functioning kidney in the long run. Therefore, kidney transplantation is always required sooner or later in cases of terminal kidney failure. This can be either a transplantation of a relative’s kidney or a transplantation of a deceased kidney. At present, suitable donor kidneys are found more often than ever before, because transplant lists are no longer limited to Germany, but cover the entire EU. Research is also currently underway to develop drug therapies for patients with nephronophthisis. Thus, it may be possible to delay progressive kidney failure with medication in the foreseeable future.
Outlook and prognosis
In general, the prognosis for all affected individuals is rather unfavorable. In most cases, terminal renal failure develops in all forms of the disease by the age of 25 at the latest. The onset of this terminal renal failure depends on the genetic defect present. In the case of an NPHP1 defect, the kidneys usually fail before the age of 25. The prognosis is less favorable in the presence of an NPHP2 defect.In this case, the kidneys usually lose their ability to function before birth or during the first year of life. In the case of an NPHP3 defect, kidney failure begins on average around the age of 19. For the NPHP3 to NPHP7 genetic defects, there are not yet sufficiently conclusive study data available, so that specialists are not able to make a more precise prognosis regarding the time of kidney failure. However, end-stage renal failure is not tantamount to a death sentence. Kidney function can be replaced with dialysis until specialists can transplant a suitable donor organ. However, the wait to receive a donor kidney can be very long because there are too few donor kidneys available. Despite dialysis, kidney failure affects the organism. For example, increased itching and yellowing of the skin often occur due to the storage of urinary substances. If left untreated, nephronophthisis leads to much earlier onset of terminal renal failure.
Prevention
Because nephronophthisis is a mutation-related inherited disease, it is almost impossible to prevent the disease.
Follow-up
Symptomatic treatment of nephronophthisis via renal transplantation means that patients receive the usual follow-up care associated with organ transplantation. In inpatient treatment, medication is administered in addition to wound care after the procedure. To ensure that the new kidney is accepted by the patient’s own body, the organ recipients must take immunosuppressants for the rest of their lives. The inpatient stay is followed by a phase of rehabilitation. The subsequent outpatient aftercare involves checking blood values at weekly intervals at the beginning, but at least every quarter of a year. In this way, it is checked whether the kidneys are functioning and efficient. A radiological examination using ultrasound, CT or MRI allows the condition of the kidney to be assessed. These follow-up examinations are important to detect whether the kidney is being rejected by the body or whether there is inflammation of the organ. If patients are treated with dialysis because no suitable donor organ has been found, hygienic regulations must be observed. This is the only way that dialysis, which is performed via a shunt (an arteriovenous fistula), can proceed without complications. Following blood purification, patients are advised to pay attention to their diet between regular sessions of hemodialysis. The intake of potassium, phosphates and salt should be kept low. Protein, on the other hand, should be consumed in sufficient amounts through the diet.
Here’s what you can do yourself
Once nephronophthisis has been diagnosed, the affected person must first seek medical treatment. Subsequently, a number of dietary measures can be taken to alleviate the symptoms and discomfort of the disease. First and foremost, a gentle diet is important, which can consist of raw vegetables, low-salt foods, and fruit juices and mineral water, among other things. The diet plan should be drawn up together with a nutritionist so that the kidney can adjust optimally to it. If complications arise, the doctor must be informed. If kidney failure is suspected, it is best to call the ambulance service. If kidney pain suddenly occurs, the doctor must be activated. It is possible that cystic kidneys have formed, which must be treated medically. Sufferers should also make sure they get enough exercise. Moderate exercise, in which the kidneys are not stressed as much as possible, helps with recovery by strengthening the immune system and promoting digestion. Since it is a hereditary disease, it is important for those affected to have the necessary genetic tests performed if they become pregnant. During genetic counseling, the risks are explained.
