Hypoplastic kidney dysplasia is a genetically and phenotypically heterogeneous group of congenital conditions that are united by underdevelopment of the urinary system due to genetic or teratogenic factors. The symptoms of this condition are quite diverse and depend on the degree of dysplasia – usually there is a lag in growth, impaired kidney function, sometimes arterial hypertension and chronic renal failure occur. Diagnosis of hypoplastic kidney dysplasia is performed by ultrasound, using blood and urine tests, and renal tissue biopsy. Treatment is symptomatic, with renal insufficiency, hemodialysis is indicated, with severe bilateral dysplasia, kidney transplantation is indicated.
General information
Hypoplastic kidney dysplasia is a group of congenital conditions that are united by underdevelopment of the kidneys of varying severity. Currently, geneticists have proved that the majority (57%) such pathologies are caused by genetic factors, about a quarter occur due to the effects of various teratogens on the fetus, in other cases, the causes of the disease are unknown. According to medical statistics, hypoplastic kidney dysplasia accounts for about 10-15% of all congenital abnormalities of the urinary system. Different types of pathology have a different mechanism of transmission from parents to a child, in some cases polygenic inheritance is noted. The sexual distribution also has no peculiarities – hypoplastic kidney dysplasia affects both boys and girls with the same probability. Quite often, such diseases are accompanied by disorders of other organs, both due to genetic factors and secondary changes due to incorrect operation of the excretory system.
Causes
Violation of the development of the urinary system in this disease occurs even at the stage of intrauterine development, which can be seen on screening ultrasound examinations of a pregnant woman. Total hypoplastic dysplasia of the kidneys is presumably caused by a violation of the differentiation of the nephrogenic germ of the mesenchyme, that is, it is an embryopathy. Specific genes whose defects are responsible for this form of pathology have not been found to date. There are theories that point to mutations that change the structure of the receptors of some mesenchymal cells, which disrupts the processes of their migration and differentiation, which causes aplastic and hypoplastic kidney dysplasia. A clear mechanism of inheritance in this form of the disease could not be found, therefore, a polygenic mechanism of its development is assumed. Total hypoplastic kidney dysplasia is rarely combined with other developmental abnormalities and primary disorders of other organs.
A similar situation develops with cystic hypoplastic kidney dysplasia – the exact mechanism of its development is unknown, but family cases with an autosomal recessive type of inheritance are described. Based on the histological structure of the kidneys of patients with this pathology, it can be assumed that the disorders develop much later than the formation of kidneys from nephrogenic mesenchyma. Cysts in this case are pathologically expanded collecting tubules, but not all of these structures undergo pathological changes – normal and functioning tubules are located next to the extensions. Often, cystic hypoplastic dysplasia of the kidneys is combined with abnormalities of the development of the ureters, gastrointestinal tract, respiratory system. In addition, multicystic kidney disease in some cases can lead to malignant degeneration of the tissues of this organ.
The most studied in genetic terms is glomeruocytosis of the hypoplastic kidney type. Its development is caused by mutations of several genes, one of which is HNF1B, located on the 17th chromosome. It encodes a special protein that is an important transcription factor in kidney, liver and pancreatic cells. Mutations of this gene lead to hypoplastic kidney dysplasia in combination with various abnormalities of the reproductive system, liver damage and early development of insulin-dependent diabetes mellitus. HNF1B defects are inherited by an autosomal dominant mechanism, according to the totality of symptoms, this form of kidney dysplasia is the most severe.
Symptoms
Regardless of the form of hypoplastic kidney dysplasia, the symptoms of this condition on the part of the excretory system are approximately the same and differ only in severity – the latter, in turn, depends on the degree of underdevelopment of the renal tissue. From early childhood, renal disorders are observed – poly- or oliguria, discoloration or turbidity of urine, pain in the lumbar region. Sometimes signs of kidney failure may increase, there may be a smell of ammonia from the mouth, from sweat or skin. In rare cases, anuria may develop with signs of acute renal failure, which requires urgent medical intervention and the appointment of hemodialysis. Children with hypoplastic kidney dysplasia often lag behind their peers in development, have a slow body weight gain.
Since quite often with this disease there are circulatory disorders in the kidneys, their juxtaglomerular apparatus produces an increased amount of renin, stimulating the renin-angiotensin system. This leads to an increase in blood pressure, which is manifested by headaches, cardiovascular disorders (arrhythmias, myocardial hypertrophy). Such disorders with a moderate degree of hypoplastic dysplasia of the kidneys can be so pronounced that they come to the fore, surpassing violations of the excretory system proper. In the absence of therapeutic measures, chronic arterial hypertension can lead to secondary kidney damage, aggravating the patient’s condition.
The cystic form of hypoplastic kidney dysplasia is often combined with atresia or ureteral stenosis, such a disorder can be either single or bilateral and requires surgical correction in infancy. But especially numerous concomitant disorders occur with glomeruocytosis of the hypoplastic type – they include malformations of the reproductive system (vaginal atresia, rudimentary or bicornuate uterus), liver damage, violation of the exocrine function of the pancreas. Patients with this form of hypoplastic kidney dysplasia develop insulin-dependent diabetes mellitus at an early age, which does not respond to drugs from the sulfonylurea group. It is important to adhere especially carefully to the insulin injection regimen – due to reduced kidney function, ketoacidotic coma with glomeruocyosis occurs much faster and harder. In the long term, it can lead to characteristic complications of this endocrine disease – trophic ulcers, retinal angiopathy, exhaustion.
Diagnostics
Hypoplastic kidney dysplasia is a fairly diverse phenotypic condition and is often combined with disorders of other organs. This leaves an imprint on diagnostics, for which many approaches and techniques are used. These include ultrasound, biochemical and general blood and urine tests, examination of specialists of various profiles (urologist, gynecologist, endocrinologist and others), glucose tolerance tests and methods of modern molecular genetics. All these studies can give a complete clinical picture of the disease and correctly diagnose the type and severity of hypoplastic kidney dysplasia.
One of the methods of the earliest diagnosis of this condition is ultrasound examination – with its help, it is possible to detect violations of the renal structure already at the stage of intrauterine development of a sick child. The most common cases of this disease are polycystic kidney disease, dysplasia of the kidneys, their reduced size, they often fuse with the formation of a horseshoe kidney. Malformations may be detected in the location of the renal arteries and veins, as well as ureters – atresia and stenosis. With glomeruocytosis of the kidneys of the hypoplastic type, anomalies of uterine development are often found – rudimentary, two-horned. Ultrasound of the liver can also reveal malformations of this organ – an unusual location of the ducts, a change in shape and relative size.
In urine tests, an increased amount of protein (proteinuria) is determined, cylinders and microhematuria are often determined. With moderate or unilateral forms of hypoplastic kidney dysplasia, urinary syndrome can be almost the only manifestation of the disease. With glomeruocytosis, hyperuricemia is a characteristic manifestation, with the development of diabetes – hyperglycemia. Glucose tolerance tests indicate a sharp decrease in the susceptibility of tissues to it. A special analysis for glycosylated hemoglobin shows its increased value, which means the long-term existence of high blood glucose levels. When examining patients with hypoplastic kidney glomeruocytosis, numerous malformations can be detected. For example, a gynecologist can detect vaginal atresia, a urologist can detect cryptorchidism and epididymal cysts, an endocrinologist can detect changes characteristic of diabetes mellitus.
A biopsy of the kidneys with their hypoplastic dysplasia can tell quite a lot about this condition – its type, severity, character. With total dysplasia of the hypoplastic type, a thickened connective tissue capsule, a large number of immature and primitive structures (underdeveloped nephrons, glomeruli, ducts) are revealed in the biopsy. These formations are surrounded by strands of loose connective tissue and smooth muscle cells. In the juxtamedullary zone, the remains of the mesonephrogenic duct are determined, all layers of the organ are moderately infiltrated by histiocytes and lymphocytes. With cystic hypoplastic dysplasia of the kidneys, the organ structures are more formed, the cysts reach a size of 3-4 millimeters, their walls are represented by modified collecting tubes.
Genetic diagnosis is currently possible only with respect to glomeruocytosis – in other cases of hypoplastic kidney dysplasia, the key genes are still unknown. At the same time, the absence of mutations in this gene does not deny the presence of hypoplastic kidney glomeruocytosis, since its cause may be defects in other, as yet unidentified genes. Prenatal genetic examination by amniocentesis or chorionic villus biopsy is also possible. Differential diagnosis should be carried out with other forms of renal dysplasia – segmental, hyperplastic, caused by both teratogenic and genetic factors, juvenile diabetes mellitus.
Treatment
There is no specific treatment for hypoplastic kidney dysplasia, only symptomatic therapy is used. It includes a reduced load on the urinary system (a clear water regime, a reduction in the amount of salts in the diet, the exclusion of certain dishes) and constant monitoring of its functional activity. With a significant weakening of the kidneys, hemodialysis may be prescribed. To reduce hyperuricemia, a diet with a reduced amount of purine bases in the diet is recommended – they are mainly contained in meat. Fructose, which is often used in the diet of diabetic patients, is also prohibited – it can also increase the level of uric acid in the blood. In addition, symptomatic treatment of diabetes mellitus, lesions and abnormalities of the development of other organs is used.
It is not uncommon for the unilateral development of hypoplastic kidney dysplasia to lead to a pronounced increase in blood pressure and related disorders. In this case, a nephrectomy of the most affected kidney is performed, but before that, the functional activity of the second organ is carefully examined. In cases where dysplasia significantly affects both kidneys, the question of possible kidney transplantation is raised. At the same time, the general condition of the body, the presence or absence of concomitant malformations and secondary changes in organs and systems are necessarily taken into account. In severe cases, only transplantation can help a patient with hypoplastic kidney dysplasia.
Prognosis and prevention
The prognosis of hypoplastic kidney dysplasia depends on many factors – the degree of underdevelopment of the organ, single or bilateral lesions, the presence or absence of concomitant disorders. In severe cases, patients die in early childhood or adolescence due to kidney failure or concomitant pathologies. But this disease is characterized by varying severity of manifestations, therefore, in milder cases, patients can live to an advanced age, especially if all the prescriptions of a nephrologist and properly prescribed symptomatic therapy are followed. The prognosis improves dramatically after kidney transplantation. Prevention of hypoplastic kidney dysplasia is possible only within the framework of prenatal diagnosis – with the help of ultrasound or genetic analyses in the case of hypoplastic glomeruocytosis.
