Glomerulocystic Disease - Classification, Pathophysiology, and Diagnosis

Introduction:-

Glomerulocystic disease is an uncommon cause of cystic kidney diseases that can occur at any age. A cystic kidney disease is a group of diseases that causes the formation of cysts (fluid-filled sacs) in and around the kidneys. These cysts may prevent the kidneys from filtering water and waste out of the body.

How Is Glomerulocystic Disease Classified?

• Familial Nonsyndromic: This group comprises autosomal dominant (a way in which the genetic trait can be passed to the child from the parent) transmitted glomerulocystic kidney disease.

• Associated With Inheritable Malformation Syndromes: This group consists of glomerulocystic disease in infants and young kids having a positive family history of polycystic kidney disease(an inherited disorder where groups of cysts develop within the kidney causing the kidneys to enlarge, impairing their function over time). This group also includes sporadic and familial diseases in older kids and adults. Except for positive family histories, no difference has been identified between the familial and sporadic cases. The sporadic cases occur with new alterations of the same disease. Heritable syndromes such as tuberous sclerosis and others have been found to be associated with this group.

• Syndromic, Mon-Mendelian: This group includes glomerulocystic kidneys due to diffuse cystic dysplasia (the antenatal obstruction of the urinary tract) and renal- hepatic- pancreatic dysplasia syndrome (a rare hereditary disorder that affects the pancreas, kidney, and liver).

• Sporadic: This group consists of all the occasionally occurring glomerulocystic kidney diseases.

• Acquired and Dysplastic Kidneys: This group comprises glomerulocystic disease, followed by hemolytic- uremic syndrome (a condition that occurs when the smaller kidney blood vessels become inflamed and eventually damaged) and obstructive uropathy (a condition in which urine cannot drain via the urinary tract).

What Is the Pathophysiology of Glomerulocystic Disease?

The pathophysiology of the formation of cysts in glomerulocystic kidney disease is vaguely understood. Before understanding the mechanism, let us understand a few terminologies associated with the kidney structure. Glomeruli are the tiny group of blood vessels that filter waste and excess fluid from the blood. The two- walled sac containing the glomeruli is the bowman's capsule. The space in between the two layers of the bowman's capsule is called the bowman's space. The various factors involved in the pathogenesis of glomerulocystic disease are:

• Obstruction of the tubes in the kidney due to inflammation of the inner part of the kidneys (medulla).

• An increase in the glomerular pressure when the fetal glomeruli start to function.

• Intake of certain drugs such as phenacetin during pregnancy.

It has been suggested that Glomerulocystic disease occurs late in gestation due to abnormality during the development of the kidneys or obstruction of the kidney tubules. Ischemia or reduced blood supply may lead to the formation of glomerular cysts in the sporadic form in adults. Baxter confirmed the presence of cysts in the glomerular region. Some recent data also suggested the abnormal narrowing of the glomerulo-tubular junction to be the primary cause of the development of glomerular cysts. An alteration or mutation of the HNF-1B (hepatocyte nuclear factor-1 beta) gene has been found to be associated with a few glomerulocystic kidney diseases. Serious vesicoureteric reflux (backflow of urine to the kidneys from the urinary bladder) leads to continuous recycling of large refluxed urine volumes that result in an enlarged urinary bladder and widened ureters (the tubes connecting the kidneys and the bladder).

What Are the Syndromes Associated With Glomerulocystic Disease?

• Down Syndrome- Down syndrome is a condition where the individual has an extra chromosome. Chromosomes contain genetic material. They define the newborns' forms and functions.

• Asplenia With Cardiovascular Anomalies- This syndrome, also known as Ivemark syndrome and right atrial isomerism, is an example of heterotaxy syndrome. These are congenital disorders characterized by heart, spleen, lung, and kidney defects.

• Multiple Acyl- CoA Dehydrogenase Deficiency- This syndrome is a broad group of conditions in which the individual cannot break down certain fats and convert them into energy.

• Jeune Syndrome- This syndrome is a form of dwarfism present since birth causing deformity in the chest wall of children. The chest area is quite small, which impairs breathing.

• Marden- Walker Syndrome- This is a genetic condition that affects the various connective tissues of the body.

• Maturity- Onset Diabetes Mellitus of the Young- This is a group of conditions where the kid has abnormally high blood sugar levels.

• Meckel- Gruber Syndrome- This is a rare hereditary condition characterized by the head, kidney, and finger malformations.

• Medullary Cystic Kidney Disease- This disease is an inherited condition affecting the kidneys. It causes scarring and reduced function of the kidneys, starting in adulthood.

• Nephronophthisis- This is a kidney disorder where there is a presence of inflammation and scarring of the kidneys that impair kidney function leading to excess urine production, excessive thirst, weakness, and tiredness.

• Orofaciodigital Syndrome- Type 1- This condition affects the development and growth of the mouth, teeth, facial features, fingers, and toes. It also causes polycystic kidney disease.

• Phocomelia Syndrome- This is a rare congenital disability that causes malformations of the limbs. Infants might have short arms and legs or completely absent limbs.

• Short Rib- Polydactyly Syndrome- This is a rare disorder characterized by short ribs, an increased number of digits, and multiple abnormalities of important organs.

• Smith- Lemli- Opitz Syndrome- This developmental disorder affects the face, head, and behavior.

• Tuberous Sclerosis Complex- This is a rare genetic disorder affecting many organ systems in the body. It causes the growth of non-cancerous tumors in the brain and other organs such as kidneys, heart, eyes, lungs, and skin.

• Zellweger Syndrome- This is a genetic disorder found in newborns. It causes serious problems with nerves, metabolism, the brain, the liver, and kidneys.

How Is Glomerulocystic Disease Diagnosed?

Several imaging techniques help in the diagnosis of glomerulocystic disease. They are:

• Ultrasound: Ultrasound uses sound waves to produce images of internal organs. In glomerulocystic kidney disease, ultrasound shows the presence of kidneys with no differentiation between the outer and the inner layers. Some cysts can also be seen.

• CT (Computed Tomography) scan: CT scan uses the combination of X- rays and computer technology to make images of the organs. In glomerulocystic kidney disease, ultrasound shows the presence of multiple cysts in both kidneys.

• MRI (Magnetic Resonance Imaging): This technique uses the magnetic field to detect an abnormality. MRI shows the presence of enlargement of both kidneys with several small cysts on the outer layer of the kidneys.

Conclusion:-

Glomerulocystic disease is a rare type of cystic kidney disease that primarily affects children. It occurs both sporadically and familially. There is the formation of cysts in the kidneys. Glomerulocystic kidney disease is a result of several hereditary and non-hereditary syndromes. Thus, a correct diagnosis of this disorder is important for understanding the link between renal cysts and renal cancers.