Hypoplastic kidney glomerulocytosis is a genetic disease manifested by underdevelopment of the urinary system in combination with damage to the liver, genitals and pancreas. It is accompanied by polycystic kidney disease, proteinuria, diabetes mellitus and malformations of other organs. The diagnosis of the disease is based on the data of ultrasound examination of the kidneys (sometimes their disorders are detected already in utero), clinical analyses and molecular genetic techniques. Treatment of hypoplastic kidney glomeruocytosis is only symptomatic, in some cases kidney transplantation is possible.
Hypoplastic kidney glomeruocytosis (diabetes and renal cysts syndrome) is a rare form of hypoplastic kidney dysplasia characterized by severe disorders of the urinary, endocrine, reproductive and other systems. For some time after the discovery of glomeruocytosis, it was believed that diabetes mellitus was the primary disorder in this disease, and the defeat of the urinary system was considered as a consequence of diabetic nephropathy. Subsequently, specialists were able to prove that hypoplastic kidney glomeruocytosis should be defined as a special poly-border pathology, almost all manifestations of which are due to genetic disorders. Geneticists have established the genetic heterogeneity of this condition and found out that patients usually have an autosomal dominant inheritance mechanism. The disease affects men and women equally often. The prevalence of hypoplastic kidney glomeruocytosis in the population has not yet been determined due to the rare occurrence of pathology.
Glomeruocytosis of the kidneys of the hypoplastic type is accompanied by a lesion of the urinary system that occurs even in the prenatal period. Currently, five genes have been identified whose mutations can cause defects in the development of kidneys and other organs against the background of insulin-dependent diabetes mellitus. The etiology and pathogenesis of the pathological condition are best studied by the example of the HNF1B gene localized on the 17th chromosome. This gene encodes a sequence of the protein of the same name, which is one of the so–called transcription factors – a protein that controls the work and expression of other genes. The most active formation of the HNF1B protein occurs in the kidneys, organs of the reproductive system, pancreas and liver, therefore, glomeruocytosis of the hypoplastic kidney type is characterized by the defeat of these anatomical formations.
The HNF1B gene has a rather complex structure (9 exons). To date, more than 70 types of mutations have been described that can cause clinical manifestations of renal cysts syndrome with diabetes mellitus. Despite the fact that the protein produced by the gene is a transcription factor, its functions in various organs are very diverse. In particular, the HNF1B protein controls the formation of renal tubules and the overall development of the kidneys, is responsible for the formation of organs of the reproductive system and determines the structure of the islets of Langerhans in the pancreas. That is why defects in the structure of this gene (and, accordingly, the protein) lead to numerous malformations. Other genes that can cause the development of hypoplastic kidney glomeruocytosis have not yet been studied enough, it is only known that they are located on different chromosomes. It is assumed that all these genes are also one or another transcription factors controlling the formation of various structures of the kidneys and other organs.
Hypoplastic kidney glomeruocytosis is characterized by a variety of disorders, some of which manifest immediately after the birth of a child. Girls have malformations of the genital organs (for example, the gaping of the genital slit in a full-term baby), boys are diagnosed with cryptorchidism or epididymal cysts. Starting from infancy, patients have signs of impaired renal function: a change in diuresis (oligo- or polyuria), lower back pain, cloudy urine and sediment in the urine. Common symptoms of pathology of the excretory system may be detected: the smell of ammonia from the mouth, an unpleasant smell of sweat and skin. In addition, jaundice due to liver damage, delayed weight gain caused by disorders in the gastrointestinal tract, and a number of other symptoms are possible.
Insulin-dependent diabetes mellitus with hypoplastic kidney glomeruocytosis occurs up to 25 years. In a number of patients, symptoms of diabetes appear even in childhood. In addition to early development, the disease is usually no different from adult diabetes, so it is referred to the group of “adult diabetes in children” (MODY). The type of this endocrine disorder caused by diabetes mellitus syndrome and renal cysts is referred to as type 5 MODY. The clinical picture of the disease includes weight loss, polyuria (not always, depends on the functional activity of the kidneys) and polydipsia. In the absence of insulin injections, clouding of consciousness and ketoacidotic coma develop. The latter occurs much faster in the presence of hypoplastic kidney glomeruocytosis, accompanied by a sharp slowdown in the excretion of ketone bodies from the body.
In the long term, the manifestations of diabetes mellitus syndrome and renal cysts are a combination of endocrine, excretory and metabolic disorders. Due to kidney disorders, the excretion of uric acid slows down, which leads to the development of gout, which is characterized by pain and inflammation of the joints and is sometimes accompanied by urolithiasis. There are disorders characteristic of patients with diabetes mellitus, including retinal angiopathy and trophic disorders in the lower extremities. The reproductive system suffers, infertility is often diagnosed in men and women due to its malformations. Girls also have frequent menstrual irregularities and amenorrhea, men may develop malignant testicular tumors against the background of untreated cryptorchidism.
Since the disease caused by a mutation of the HNF1B gene is accompanied by multiple lesions of organs and systems, a large number of techniques are used to diagnose this pathology. The examination program includes various types of ultrasound examinations, consultations of medical specialists of various profiles (urologist, endocrinologist, gynecologist, etc.), urine and blood tests (both general and biochemical) and methods of molecular genetics. It is on the basis of the results of all these diagnostic techniques that glomeruocytosis of the hypoplastic kidney type can be reliably determined. Additional studies may also be required: analysis for the level of glycosylated hemoglobin, glucose tolerance test, and others.
The first manifestations of the disease can be detected using ultrasound diagnostics. The pathology of the kidneys in the fetus is often determined already during screening ultrasound in pregnant women. Most often, cysts form in the kidneys, sometimes multiple (polycystic kidney disease), the organs themselves are reduced in size and can fuse together (this phenomenon is called a horseshoe kidney). With hypoplastic kidney glomeruocytosis, an abnormal arrangement of organ vessels and their branching can also be determined. An unusual localization of the ureter is often found. Pelvic ultrasound in women with hypoplastic kidney glomeruocytosis often reveals malformations of the reproductive system (bicornular or rudimentary uterus). Ultrasound of the liver indicates an abnormal structure of the organ (a change in its shape and size).
In urine tests, proteinuria, hyaline and other cylinders are detected. Microhematuria and glucosuria manifest as diabetes mellitus develops. Due to pronounced proteinuria, a decrease in total protein and an increase in the concentration of lipoproteins may be detected in the biochemical analysis of blood. An increase in the level of uric acid in the blood plasma (hyperuricemia) is also a constant manifestation of hypoplastic kidney glomeruocytosis. As diabetes mellitus increases, glucose concentration increases with the development of hyperglycemia and glucosuria. An additional analysis of the level of glycosylated hemoglobin shows its increase – this serves as evidence of prolonged hyperglycemia in the patient.
When conducting consultations of narrow specialists, numerous violations are revealed. A gynecologist often detects vaginal atresia, a urologist diagnoses epididymal cysts and often cryptorchidism. All of the above data provide the basis for genetic diagnosis, which is carried out by direct sequencing of the sequence of the HNF1B gene. Sometimes, with clinically pronounced hypoplastic kidney glomeruocytosis, this study does not confirm the presence of genetic defects in HNF1B, which does not exclude mutations in other genes that can cause the development of the disease. Differential diagnosis of glomeruocytosis is performed with other renal dysplasia and diabetes mellitus.
Specific treatment of hypoplastic kidney glomeruocytosis has not been developed, symptomatic and supportive therapy is used. Constant monitoring of the functional activity of the kidneys is necessary, therefore, patients should be registered at the dispensary and regularly undergo examination by a nephrologist and an endocrinologist. To reduce the load on the urinary system, a balanced diet is prescribed, it is advised to observe the correct water regime and limit salt intake. Patients are recommended to reduce the amount of meat and fructose in the diet, since the components of these foods can turn into uric acid during metabolism, exacerbating the manifestations of hyperuricemia and gout. With symptoms of acute or chronic renal failure, a course of hemodialysis is performed.
The treatment plan for diabetes mellitus is made taking into account the lack of reaction to sulfonylureas. Regular insulin injections are needed. You should stick to a low-carb diet and calculate the amount of sugar in the diet. Symptomatic treatment of hypoplastic kidney glomeruocytosis is also performed with damage to the liver, pancreas and organs of the reproductive system. Surgical intervention may be required to correct cryptorchidism and other developmental abnormalities. The decision to transplant a kidney with its pronounced lesion is made taking into account the general condition of the patient and the degree of violations by other organs.
Prognosis and prevention
The prognosis of hypoplastic kidney glomeruocytosis is usually unfavorable, due to the early appearance of symptoms (many of which are congenital), their severity, and a wide range of lesions of various organs and systems. With a severe course of the disease, a fatal outcome can occur even in childhood due to a combination of excretory disorders and diabetes mellitus. With adequate symptomatic therapy, lifelong adherence to the rules of diet and water regime, hypoplastic kidney glomeruocytosis sometimes has a benign course, some patients manage to live to old age. Prevention of the disease is reduced to prenatal genetic diagnosis, which is especially indicated in the presence of this condition in close relatives.