Renal dysplasia occupies prominent place among malformation of urinary system.
Renal dysplasia is a heterogeneous group of diseases associated with violation of renal tissue. Morphologically in basis of dysplasia there is a violation of differentiation of nephrogenic blastema and ureteral branches sprout with presence of embryonic structures in the form of foci of undifferentiated mesenchymal and primitive ducts and tubules. Mesenchyme is presented by cambial pluripotent cells and collagen fibers, it can form dysontogenetic derivatives of hyaline cartilage and smooth muscle fibers.
Currently, there is no standard classification of renal dysplasia. Most of authors on the basis of morphological manifestations distinguish simple and cystic dysplasia, by localization - cortical, medullary, and cortical-medullary. Depending on prevalence there are focal, segmental and total dysplasias.
Causes of renal dysplasia
Genetic disorders have major importance in the development of renal dysplasia (57%), share of teratogenic effect is much less (16%), and nearly in one third of patients factors that led to dysplasia are unknown.
Renal dysplasia without cystic deformation
Simple total dysplasia in literature is often described as hypoplastic dysplasia. Among congenital malformations of urinary system it makes up 2.7%.
There are aplastic and hypoplastic options. During aplastic dysplasia in case of bilateral renal injury death occurs within first hours or days of life.
Hypoplastic variant is characterized by early manifestation of urinary syndrome, characterized by mosaicism, and early development of chronic renal failure.
Morphological study notes decrease in weight of kidneys, they have a lobed surface, division between layers is not always clear-cut, and sometimes there is a slight expansion or hypoplasia of ureters. Microscopically primitive structures are detected: many glomeruli are reduced in size, vascular loops are atrophic, and capsule is thickened. Form of glomeruli may be S-shaped or ring-shaped, many of them are hyalinized and sclerotic. Gomeruli are located botryoidal, are surrounded by loose connective tissue with focal accumulations of lymphoid and histiocytic cells. In medulla there are a lot of primitive ducts and tubules, which are immature forms of various stages of embryonic development. Primitive ducts are mainly detected in juxtamedullary area; these are residues of mesonephroid duct. Presence of shadows of smooth muscle cells and connective tissue fibers around them is a characteristic feature. Presence of primitive structure reflects delay in ripening of nephron.
Accidental detection of disease, presence of multiple stigmas of dysembryogenesis, lag in physical development are of importance for diagnosis.
Furthermore, it should be noted that hypoplastic dysplasia can be detected amid intercurrent illness, wherein extrarenal syndromes may be absent or mild. Urinary Syndrome manifests itself with hematuria with mild proteinuria. Manifestations of disease are very heterogeneous. Often there can be proteinuric option with significant loss of protein, but edema syndrome is relatively rare, even with significant proteinuria and nephrotic syndrome is characterized as incomplete. Dynamic observation of child shows that clinical picture in future is characterized by nephrotic syndrome, presence of tubulointerstitial changes, often with of urinary tract infection.
Development of gipoimmunnyh or immunodeficient states is typical for children with hypoplastic dysplasia, which explains connection of heavy and frequent intercurrent diseases with progression of pathological process in kidneys. Lack of high blood pressure is important feature of nephropathy, hypotension is more common. High blood pressure occurs at development of chronic renal failure.
Differential diagnosis is carried out with hereditary nephritis, interstitial nephritis, and various forms of glomerulonephritis. In order to establish definitive diagnosis kidney biopsy is shown.
Course of disease is torpid, there is no cyclical or wave-like nature of symptoms, drug therapy is usually ineffective.
Treatment is symptomatic. Forecast is serious, with early development of chronic renal failure and the need to organize replacement therapy - hemodialysis or peritoneal dialysis, kidney transplantation.
Simple focal dysplasia is diagnosed, usually during renal biopsy or autopsy. Clinical manifestations of disease are absent.
Morphological study does not show significant changes in weight of kidney. In some cases, there is a decrease in thickness of crust. This nephropathy is diagnosed on basis of histological changes detected by microscopy. Simple focal dysplasia is characterized by presence primarily in renal cortex of clusters of primitive glomeruli and tubules surrounded by connective tissue fibers and smooth-muscle cells sometimes cartilage is detected. Polymorphism of convoluted tubule epithelium is characteristic, where adjacent cells differ in size, configuration, by set and number of intracellular organelles. In some of children in kidney tubular lumen may be extended. Glomerular cysts can be detected, but their number is negligible. The mononuclear cells of mesenchymal species are detected in stroma.
Simple segmental dysplasia (kidney Ask-Upmark) is rare (0.02% of all autopsies). With this type of dysplasia, kidney is reduced in size, transverse groove on outer surface at site of hypoplastic segment is clearly apparent, number of pyramids is reduced. Morphological changes are caused by dysembryogenesis of vessels in certain segments of kidney followed by violation of differentiation of tissue structures due to changes in blood supply to these areas. Usually hypoplasia of respective branches of arteries is revealed. Presence of primitive mesonephroid ducts in hypoplastic segment, surrounded by smooth muscle cells and foci of hyaline cartilage, is characteristic feature. In addition, sclerosis, hyalinosis of glomeruli, tubular epithelium atrophy with expansion of their lumen, signs of fibrosis and cell infiltration, interstitial develop.
With simple segmental dysplasia development of resistant hypertension at an early age is dominant feature, and it is more common in girls. Children complain of headaches, cramps are possible, changes in retinal vessels develop early.
Pain in form of abdominal pain is one of main clinical symptoms; polyuria and polydipsia appear early enough as manifestations of tubulo-interstitial syndrome. In some cases, there is lag of body weight and growth of children. Urinary syndrome occurs mainly as proteinuria against background of microhematuria and moderate leukocyturia.
Cystic renal dysplasia
Depending on extent total, focal and segmental forms of cystic dysplasia are distinguished.
Among total forms of cystic dysplasia aplastic, hypoplastic, hyperplastic and multicystic options are distinguished.
Aplastic cystic dysplasia (multicystic of rudimentary kidney) is 3.5 % of all congenital diseases of urinary system and 19% of all forms of cystic dysplasia. Kidneys are significantly decreased in size, are formless with formation of cysts with diameter of 2-5 mm, renal parenchyma is almost completely absent, ureter is absent or there is its atresia. Microscopically large number of cysts is detected both glomerular and tubular, and primitive ducts and foci of cartilage. Bilateral lesion is incompatible with life. Unilateral rudimentary kidney is often detected during random inspection, and second kidney is often also abnormal.
Clinical picture depends on the state of the second kidney; in which pyelonephritis often develops due to presence of dysplasia in it.
Diagnosis is based on ultrasound examination data, excretory urography, rino and scintigraphy. At cystoscopy mouth of ureteral at side of rudimentary kidney is usually absent or stenotic.
Hypoplastic cystic dysplasia
(Multicystic of hypoplastic kidneys) is 3.9% of all defects of urinary system, and among cystic dysplasia - 21.2%. Kidneys are reduced in size and weight. Glomerular cysts are usually located in subcapsular zone; their diameter varies and can reach 3-5 mm. Tubular cysts are found both in cortex and in medulla. Fibrosis of connective tissue and presence of primitive ducts are more significant in medulla. Cysts are large and resemble cystic dilated collecting ducts. Renal parenchyma is partially preserved. Among pathologically changed areas there are collecting duct of normal structure. Pelvis may be unchanged, more frequently it is hypoplastic, as ureter. Hypoplastic cystic dysplasia is often combined with malformations of lower urinary tract, gastrointestinal tract, cardiovascular system and other organs.
Bilateral lesion early leads to development of chronic renal failure. As a rule, in case of one-sided case of dysplasia second kidney has certain manifestations of dysembryogenesis.
Clinical picture is due to pyelonephritis, chronic renal failure, rate of progression of which depends not only on number of intact hypoplastic kidney parenchyma, but also on extent of second nonhypoplastic kidney, but, as a rule, having dysplastic elements.
Hyperplastic cystic dysplasia often accompanies Patau syndrome. It is two-way process. Kidneys are increased in size, covered with multiple cysts. At microscopy primitive channels, large number of cysts in cortical and medullary layers are revealed. Fatal outcome usually occurs at early age.
Multicystic dysplasia (multicystic kidney) is malformation in which kidneys are increased in size, there are many cysts different in shapes and sizes (from 5 mm to 5 cm), between which parenchyma is practically absent.
At microscopy primitive ducts and glomeruli are revealed between cysts, areas of cartilage may occur. With bilateral lesions death occurs in first days of life. In case of unilateral lesion diagnose is put incidentally during palpation of hillocky tumour formation or on results of ultrasound. In case of unilateral multicystic malformations of second kidney are possible (often hydronephrosis), heart, gastrointestinal tract diseases, and others.
Disease can be manifested by the presence of dull or paroxysmal pain in abdomen and in lumbar region. Discovery of hypertension is possible.
In case of multicystic nephrectomy is performed in case of risk of development of malignancy.
In case of medullary dysplasia (cystic dysplasia of medulla, medullary cystic disease, Fanconi nephrophthisis) kidneys are usually reduced in size, often embryonic lobulation persists. Cortex is thinned; medulla is expanded due to large number of cysts with diameter of 1 cm, cystic dilation of collecting ducts is characteristic. At microscopy decrease in size of many of glomeruli is marked, part of them are hyalinized and sclerotic, interstitial is also sclerotic, in stroma there is lymphoid infiltration.
Clinical manifestations of disease usually develop after age of 3, most often between ages of 5-6 years "Fanconi syndrome" appears - polyuria, polydipsia, fever, retarded physical development, repeated vomiting, dehydration, acidosis, anemia, rapid progression of uremia.
Among laboratory signs hypoproteinemia is characteristic, urinary syndrome usually occurs with small proteinuria. Due to increased loss of salt hyponatremia, hypocalcemia and hypokalemia develop.
Acidosis develops due to large bicarbonaturia, breach of acido- and ammoniogenesis.
Treatment is symptomatic. With development of chronic renal failure hemodialysis or peritoneal dialysis and kidney transplantation are shown.
Multilocular cyst (lobular cystic renal dysplasia) is focal form of cystic kidney dysplasia and is characterized by presence of one of its poles of multi cyst, limited by capsule from normal kidney tissue and divided internally by partitions.
Clinical picture is characterized by appearance of pain of varying severity in abdomen and in lumbar region due to violation of outflow of urine due to compression by large cyst of renal pelvis or ureter. Furthermore, due to possible compression of abdominal organs, there are symptoms that simulate their disease.
In diagnosis radiological examination methods are crucial, including nephrotomography and angiography.
In case of cortical dysplasia (microcystic kidney, congenital nephrotic syndrome of "Finnish" type) kidneys are not changed in size, lobulation can be preserved. Minor glomerular and tubular cysts with diameter of 2-3 mm are detected. From birth, there is picture of nephrotic syndrome. Congenital nephrotic syndrome of "Finnish" is hormone- resistant with unfavourable prognosis. There is early development of chronic renal failure.
Polycystic kidney disease
Polycystic kidney disease takes special place among cystic dysplasia. Occurrence of polycystic is associated with impaired embryonic development of kidneys, often in form of lack of connection of primary collecting duct with part of nephron, developing from metanephrogenic neoplasms. Blind tubules formed in this continue to evolve, they accumulate primary urine, which stretches them, causing atrophy of epithelium. At the same time connective tissue, surrounding duct grows.
Size of cysts varies widely: in addition to small, visible only with magnifying glass or a microscope, there are large, up to several centimeters in diameter. Large number of thin-walled cysts in cortex and medulla of kidneys gives them view of honeycomb at cut. Histologically, cysts are presented by dilated tubules with cubic epithelium, or take form of cavities with thick connective tissue wall and sharply flattened epithelium. E. Potter (1971) described cysts, associated with expansion of cavity of Bowman's capsule of glomeruli, without change of tubules. Cysts can be empty or contain serous, protein liquid, sometimes coloured with blood pigments, uric acid crystals. Strom of kidney in polycystic is sclerotic, often with focal lymphoid-cell infiltration, and in children under 1 year - with foci of extramedullary hematopoiesis. Sometimes, in stroma parts of cartilage or smooth muscle fibers are revealed. Amount and type of glomeruli and tubules disposed between cysts may be different.
Disease manifests itself in two main forms, which differ in character of inheritance, clinical manifestations, morphologic picture, "infantile" and "adult" type.
Polycystic of "infantile" type (small cystic kidney) has autosomal recessive mode of inheritance. Kidneys are significantly increased in size and weight. In cortex and medulla multiple cysts of cylindrical and fusiform are defined. Cysts are demarcated by meager layers of connective tissue. Cysts are also found in liver and other organs. Clinical manifestations depend on number of affected tubules. With defeat of up to 60% of tubules, death from progressive uremia occurs in first 6 months. Results of O.V.Chumakovoy (1999) do not support classic idea of early mortality of children with autosomal recessive polycystic form and show that their life can be quite large, even at early detection of clinical symptoms. However, chronic renal failure develops in them earlier than in autosomal dominant polycystic form. In these patients, in clinical picture symptoms of liver failure play leading role. In clinic there is often micro, macrohematuria and increased blood pressure. Polycystic is often complicated by pyelonephritis with torpid course.
In polycystic of "adult" type (large cystic kidney) kidneys are almost always increased in size, their weight of each in adults is up to 1.5 kg or more. In cortex and medulla there are numerous cysts of 4-5 cm in diameter.
Clinical symptoms appear in adolescence: pain in lumbar region, palpation of tumour formation in abdominal cavity, arterial hypertension. Urinary syndrome manifests itself by hematuria. Often pyelonephritis joins. Functionally, kidneys are preserved for many years, and then hyposthenuria, decreased glomerular filtration rate and azotemia appear.
Diagnosis is based on family history, ultrasound data, excretory urography, in which there is increase in kidney`s contours, flattening of pelvis with elongation and compression of cups.