Nephronophthises are kidney diseases that are due to a genetic mutation or deletion. End-stage renal failure occurs within the framework of these seven forms of disease by the age of 25 at the latest. The only curative therapy available so far is transplantation.
What is nephronophthisis?
Nephronophthisis is a genetic kidney disease with chronic inflammatory properties. The interstitial kidney tissue is the main target of the diseases. So far, seven different hereditary diseases have been assigned to this group:
- juvenile nephronophthisis
- infantile nephronophthisis
- adolescent nephronophthisis
The remaining three diseases are referred to as NPHP4, NPHP5, NPHP6 and NPHP7 and have not been particularly well researched. See phonejust for Melanin Deficiency Meaning.
Until the 1970s, researchers described nephronophthisis as medullary cystic kidney disease. Histologically, these diseases can hardly be differentiated from each other. However, the inheritance of medullary cystic kidney diseases differs from the inheritance of nephronophthisis. Instead of an autosomal dominant inheritance, nephrophthisis is an autosomal recessive inheritance. The frequency of all forms is given at a ratio of about 1:100,000.
The cause of all nephronophthisis is a gene mutation or gene deletion. The diseases are genetically determined and 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. If mutated or deleted, the protein loses its function. In contrast, infantile nephronophthisis 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 genetic defect is on chromosome 3 gene locus q21-q22. The fourth form of nephronophthisis is triggered by a mutation or deletion on chromosome 1 gene locus p36.22, where the protein nephroretinin is encoded. In the fifth variant, there is a deletion or mutation on chromosome 3 gene locus q21.1 that affects the protein nephrocystin-5. NPHP6 has been linked to an abnormality at chromosome 12 gene locus q21.33 and NPHP7 has an impaired zinc finger protein.
Symptoms, Ailments & Signs
Enormous salt losses occur in all nephronophthises, which dehydrate the patient considerably and usually trigger a shift in the electrolyte balance. The urine can no longer be brought to a concentration of 800 mosm*kg−1H2O. Azotemia occurs. Those affected therefore have an above-average level of nitrogenous metabolites in their blood.
Anemia is also one of the symptoms of nephronophthisis. In addition, hypokalemia, i.e. potassium deficiency, occurs. Hyperacidity is just as common. The tubules of the kidneys are atrophic and cystically dilated. Unlike in healthy patients, the tubules lie at the corticomedullary border.
Cysts form primarily on the collecting ducts of the renal medulla and on the distal convolute of the kidneys. Kidney function gradually decreases and ends in end-stage renal failure. Only in adolescent nephronophthisis does terminal renal failure occur after the adult has reached majority.
Diagnosis & course of disease
Doctors usually diagnose nephronophthisis using blood tests, urine samples, and kidney function scintigraphy, as well as imaging tests. Both ultrasound and MRI can be used for imaging. As a rule, nephronophthisis remains undetected for a long time until severe symptoms appear.
The prognosis for those affected is rather unfavorable. End-stage renal failure occurs in all patients by the age of 25 at the latest. The adolescent form is associated with the comparatively best prognosis, since kidney failure in this subspecies is not to be expected until after the adult has come of age.
Complications always occur in patients suffering from nephronophthisis. All genetic defects sooner or later lead to kidney failure. However, the point in time at which terminal kidney failure occurs depends on which gene defect is involved. After that, life can be sustained with the help of dialysis until a kidney transplant is performed.
In the case of 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 kidney failure could still be postponed. The prognosis for the NPHP2 defect is even worse. Here, terminal kidney failure often occurs before birth, but at the latest within the first year of life.
The course of the NPHP3 defect is somewhat more favourable. Terminal renal 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 also occurs here.
The patient requires constant medical treatment and monitoring, otherwise there will be an accumulation of urinary substances in the blood, potassium deficiency, anemia (low blood count) and metabolic acidosis (overacidification). Despite constant blood purification, a total failure of the kidneys can occur, a life-threatening condition that can only be remedied with a kidney transplant.
When should you go to the doctor?
When you have to go to the doctor with nephronophthisis depends, among other things, on the type of disease and its severity. Basically, kidney problems should be clarified if they persist for more than a few weeks. Signs of anemia and deficiency symptoms require a medical examination. You should also see a doctor if you have hormonal problems or kidney pain. Anyone who already suffers from kidney disease should report these symptoms to their doctor. Medical advice is also required if an existing illness suddenly becomes more severe or if unusual symptoms occur that were not noticed before.
The doctor will then carry out a comprehensive examination and use this to make a diagnosis. If this is done early, serious complications can be avoided. Therefore, the first signs must be clarified and, if necessary, treated. The right contact person is the family doctor, an internist or a nephrologist. If the symptoms are severe, the person concerned should be taken to a hospital immediately. It may also be necessary to visit a specialist kidney disease clinic.
Treatment & Therapy
There is no causal therapy for patients with nephronophthisis. Treatment is limited to relieving symptoms. The gradually progressing renal insufficiency cannot be stopped with the current therapy options. The only chance of a complete cure is a kidney transplant. In more than ten percent of all those affected, the diagnosis is only made when end-stage renal failure is already present.
After the onset of end-stage renal failure, there are several treatment options available as renal replacement therapies. The options for dialysis are hemodialysis and peritoneal dialysis. All dialysis procedures are blood purification procedures that are intended to replace the blood-purifying and detoxifying functions of the kidneys. Hemodialysis is an extracorporeal procedure and takes place outside of your own body.
Peritoneal dialysis, on the other hand, is an intracorporeal procedure and is applied inside the patient’s body. The former procedure is used significantly more frequently as renal replacement therapy. Dialysis cannot replace a functioning kidney in the long term. Therefore, sooner or later, a kidney transplant will always be necessary in end-stage renal failure. This can either be a relative’s kidney transplant or a deceased’s kidney transplant.
Currently, suitable donor kidneys are found more often than ever before, because transplant lists are no longer limited to Germany, but refer to the entire EU. Research is also currently involved in developing drug therapies for patients with nephronophthisis. In the foreseeable future, it may be possible to delay the progression of kidney failure with medication.
Outlook & Forecast
In general, the prognosis is rather unfavorable for all those affected. In all forms of the disease, terminal renal insufficiency usually develops by the age of 25 at the latest. The onset of this definitive kidney failure depends on the genetic defect present in each case. 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 around the age of 19 on average. So far, there are not sufficiently meaningful study data on the gene defects NPHP3 to NPHP7,
End-stage renal failure, however, is not equivalent to a death sentence. The function of the kidneys can be replaced by dialysis until specialists can transplant a suitable donor organ. However, the waiting time to receive a donor kidney can be very long because there are not enough donor kidneys available. Despite dialysis, kidney failure affects the organism. Increased itching and yellowing of the skin are often seen due to the storage of urinary substances. If left untreated, nephronophthisis leads to terminal renal insufficiency that sets in much earlier.
Since nephronophtheses are mutation-related hereditary diseases, the diseases can hardly be prevented.
The symptomatic treatment of nephronophtis via a kidney transplant means that the patients receive the usual aftercare for an organ transplant. In inpatient treatment, in addition to wound care after the procedure, medication is used. In order for the new kidney to be accepted by their own body, the organ recipient must take immunosuppressants for life.
The inpatient stay is followed by a rehabilitation phase. The subsequent outpatient follow-up includes checking the blood values at weekly intervals, but at least every three months. This checks whether the kidneys are functioning and efficient. A radiological examination using ultrasound, CT or MRI enables the condition of the kidney to be assessed. These follow-up tests are important to detect if the kidney is being rejected by the body or if the organ is inflamed.
If those affected are treated with dialysis because no suitable donor organ was found, hygienic regulations must be observed. This is the only way that dialysis, which is carried out via a so-called shunt (an arteriovenous fistula), can proceed without complications. After the blood purification, patients are advised to watch their diet between regular hemodialysis sessions. The intake of potassium, phosphates and salt should be kept low. Protein, on the other hand, should be ingested in sufficient quantities through food.
You can do that yourself
If nephronophthisis has been diagnosed, the person concerned must first seek medical treatment. A number of dietary measures can then be taken to alleviate the symptoms and signs of the condition.
First and foremost, a gentle diet is important, which can consist of raw food, low-salt foods, fruit juices and mineral water, among other things. The nutrition plan should be drawn up together with a nutritionist so that the kidneys can optimally adjust to it. If complications arise, the doctor must be informed. If kidney failure is suspected, it is best to call the emergency services. If kidney pain suddenly occurs, the doctor must be activated. It is possible that cystic kidneys have formed, which must be treated medically.
Patients should also ensure they get enough exercise. Moderate exercise that doesn’t put too much strain on the kidneys helps with recovery by boosting the immune system and aiding digestion. Since it is a hereditary disease, it is important for those affected to have the necessary genetic tests carried out during pregnancy. Genetic counseling explains the risks.