OVERVIEW
Autosomal recessive polycystic kidney disease is a hereditary nephropathy characterized by fusiform expansion of the renal collection and congenital hepatic fibrosis. It is a rare disease that can occur in the perinatal period, neonatal period, infancy, adolescence and even adulthood, with equal incidence in both sexes and no significant difference between different races. about half of the affected children die of respiratory failure or renal failure in the first few hours to days after birth, and the ones who can survive the neonatal period can maintain normal renal function by 15 years of age. The majority of patients can maintain normal renal function until the age of 15.
Causes
The causative gene is PKHDl, localized on chromosome 6, and 63 different forms of mutation have been identified. The gene encodes a transmembrane protein, mostly extracellular, which may play a key role as a receptor in the development of renal collecting ducts and bile ducts and maintenance of normal tubular lumen structure. Abnormal function of the ciliary structure of this protein may also be the molecular basis for the development of this disease.
Symptoms
Clinical manifestations are diverse, and the severity of the disease varies even among patients from the same family.
1. Increased kidney size
The volume of the kidneys of the affected children is the largest at the age of l to 2 years, and gradually shrinks with age, reaching stability at the age of 4 to 5 years. The prenatal manifestation of the mother’s amniotic fluid is too small, the fetal bladder is empty, the size of the kidneys increase, echo enhancement, the child is often difficult to deliver because of the huge size of the kidneys.
2. Liver fibrosis
With age, liver symptoms and signs become more obvious, including portal vein fibrosis and intrahepatic bile duct dilatation. Portal vein fibrosis often leads to portal hypertension, which is manifested by gastrointestinal bleeding, portal vein thrombosis and splenomegaly. However, dilatation of intrahepatic bile ducts seldom leads to cholangitis, and liver function involvement is rare. Few cases may progress to cholangitis or cholangiocarcinoma.
3. Renal failure
The progression is slow, with some children progressing to end-stage renal failure by the age of 15 years, and 70% of patients entering end-stage renal failure by the age of 25 years. Renal failure often leads to growth retardation, anemia and renal bone disease in children; a significant proportion of adult patients maintain normal renal function. 4. Other symptoms
Impaired renal concentrating function is manifested by frequent urination, increased urine output and hyponatremia. In addition to enlarged kidneys in the neonatal period, children often have renal failure and respiratory failure due to pulmonary dysplasia with mediastinal pneumothorax and pneumothorax, which can also be combined with pneumonia. Hypertension is common in infancy and childhood, especially more severe in the first few months of life, and is often associated with cardiac hypertrophy and congestive heart failure.
Examination
1. Imaging examination
(1) Ultrasound: It is the most commonly used method for initial screening and prenatal diagnosis. In severe cases, amniotic fluid decreases and bladder emptying appear at 12 weeks of pregnancy; most patients have characteristic manifestations in infancy or childhood, such as increased renal volume, cortical and medullary echogenicity, unclear renal collecting system, and blurred demarcation between kidneys and the surrounding tissues; the renal ultrasound manifestations of adult patients have changed, and the renal volume may be normal but multiple cysts less than 1.5cm can be seen. The corticomedullary demarcation is blurred, and the dilated collecting duct wall reflects the ultrasound and enhances the cortical echogenicity.
(2) CT and magnetic resonance imaging are also commonly used. Magnetic resonance cholangiography can detect lesions missed by ultrasound, but is not indicated in children under 3 years of age.
2. Histopathologic examination
Liver biopsy is mainly performed to show portal vein fibrosis, etc.
3.Genetic examination
Direct detection of PKHDl gene to prove the existence of gene mutation is an important auxiliary examination.
Diagnosis
With typical clinical manifestations such as increased volume of both kidneys, congenital liver fibrosis, etc., there is a history of intergenerational family inheritance, and the ultrasound performance of kidneys of the child’s parents is normal. Ultrasound examination of the child shows increased renal volume, cortical and medullary echogenicity, atypical cases must sometimes rely on liver biopsy to confirm the diagnosis, due to the PKHDl gene localization clone, direct detection of the gene mutation makes the diagnosis of this disease more accurate.
Differential diagnosis
It mainly needs to be differentiated from autosomal dominant polycystic kidney disease. It is not difficult to differentiate typical cases, the latter is autosomal dominant, clinical manifestations do not have symptoms of hepatic portal vein fibrosis, but sometimes it is difficult to identify atypical cases, and a few patients with spontaneous mutations do not have a positive family history, and a very small number of them may be combined with congenital hepatic fibrosis, so it can not be completely excluded, and then it is necessary to carry out a genetic test in order to make a correct diagnosis.
Complications
Some patients may have urinary tract infections.
Treatment
Symptomatic treatment is the mainstay, and there are no effective measures or drugs to cure the disease.
1. Neonatal treatment
Treatment focuses on correcting the respiratory failure of the child, and the application of mechanical ventilation and supportive therapy greatly improves the survival rate of the child. Other complications such as mediastinal pneumoperitoneum, pneumothorax and heart failure should be treated accordingly.
2. Infancy and adolescence treatment
(1) Hypertension: Most of the patients have symptoms of hypertension, and only very few of them can disappear on their own. Generally, drug treatment is effective, and controlling blood pressure can significantly improve the prognosis. Patients usually respond well to treatment, and salt restriction and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are preferred as antihypertensive drugs.
(2) Edema: the mechanism of edema is still unknown and may be related to impaired hepatic and renal function. Restricting salt intake and applying diuretics can reduce edema, but loop diuretics with strong diuretic effect are usually needed.
(3) Renal failure: dialysis treatment or renal transplantation can be used according to the specific situation. However, considering the patient’s concomitant combination of hepatic fibrosis, susceptibility to infection and poor wound recovery, he should be treated as a high-risk patient.
(4) Hepatobiliary system symptoms: rupture and bleeding of esophageal-fundus varices may be life-threatening, requiring timely and effective treatment. In addition, splenomegaly is often accompanied by hypersplenism, resulting in anemia, leukopenia and thrombocytopenia, and the principle of treatment at this time is portal-cavity shunt, splenic-kidney shunt can effectively reduce the portal pressure, but the risk of surgery is significantly higher than that of general patients. Splenectomy can correct hematologic abnormalities, but patients with reduced immune function are prone to complications of infection.
(5) Urinary tract infection: rational application of antibiotic treatment.
(6) Other complications: in addition to providing sufficient energy and nutritional supply, apply recombinant human growth hormone treatment, which is effective and has no adverse effect on renal function, and recombinant human erythropoietin can treat children with renal anemia.
Prognosis
The condition of patients with neonatal onset is more serious, if they can be actively and effectively treated, the prognosis of children who have passed the neonatal period is generally better. Generally, renal failure in neonatal period is less likely to cause death, and as the respiratory status improves, the renal function will also be improved. As the respiratory condition improves, the renal function will also improve. Patients who have passed the neonatal period will have impaired renal function as they grow older, liver symptoms will worsen, and the incidence of renal failure will gradually increase.