Poly cystic Kidney Disease: Genetic and Pathogenesis

Introduction to Polycystic Kidney Disease

As the name suggests, polycystic kidney disease (PKD) is a condition characterized by the formation and growth of cysts in the kidney. This disease is a genetic disorder with two different types. The first is autosomal dominant polycystic kidney disease (ADPKD) and is the more common of the two. The second type is autosomal recessive polycystic kidney disease (ARPKD), which is much rarer (Crow, 2017). Being a genetic disorder, PKD can be assumed to have existed throughout human history. However, it was encountered and observed medically in 1586, with the death of the King of Poland, Stephen Bathory. After his death, his Surgeon Jan Zigulitz recorded that the king’s kidneys were large as a bull, with a bumpy and uneven surface. In the 18th century, doctors and historians reading these records concluded that PKD must have been the cause of his death. The term “polycystic kidney” was first used in 1888 by Flix Lejars, who characterized the disease as affecting both kidneys, and having clear and specific symptoms. In 1994, the disease was discovered to have a cause that was genetic in nature, with around 85% of ADPKD patients possessing the PKD-1 gene on chromosome 16 (Balat, 2016).Poly cystic Kidney Disease: Genetic and Pathogenesis

ADPKD affects around 4. 3 per 10, 000 people, or 0. 043% of the population. It is almost twice as likely for women to be diagnosed in early adulthood because of their receiving of ultrasound testing during childbearing years. On the other hand, males are commonly diagnosed at the 65 years and older demographic, indicating that there is greater possibility for ADPKD to be undiagnosed in young men. In the United States, ADPKD affects about 140, 000 patients, making it a relatively rare disease. On the other hand, ARPKD affects 1 in 20, 000 to 40, 000 people (Willey et al., 2019). PKD will not cause signs or symptoms while the cysts are small. Thus, PKD will be difficult to detect without being tested. Once the cysts are 0. 5 inches or larger, symptoms will begin to manifest themselves. Symptoms include high blood pressure, blood in urine, excessive urination, headaches, and pain in the abdominal area or in the back. Furthermore, this condition will lead to the formation of clusters of cysts in the kidney and potentially other organs like the liver, pancreas, and testes. PKD is also associated with aneurysms in the arteries or the brain, and diverticula of the colon (Phillips, 2018). Generally, the only risk factor for this disease is having inherited this gene from one’s parents or grandparents. However, it is possible for this disease to occur without parents carrying the mutation due to a mutation occurring in the embryonic development process. (Iliuta et al., 2017)

Pathophysiology

PKD is an inherited disease that is caused by mutations occurring in the genes, that have been inherited from one’s parents. In ADPKD, 85% of cases have the mutation occurring in the PKD1 gene, located on chromosome 16p13. 3. In the remaining 15% of cases, the mutation occurs in the PKD2 gene, located on chromosome 4q21-23. The PKD1 gene codes for the protein polycystin-1 (Igarashi & Somlo, 2002). This protein contains a long extracellular N-terminal portion and eleven transmembrane domains. The extracellular portion contains multiple domains, including two leucine-rich repeat areas, that are able to bind collagen, fibronectin, and laminin. The protein also may be able to bind carbohydrates and the protein-ligand. The PKD2 gene codes for the protein polycystin-2. In ADPKD, all the cells in the kidney carry the mutated gene, but only some of the nephrons (the kidney’s functional subunit) present cysts, with each nephron having a few cysts. Thus, ADPKD is a focal disease that does not impact all of the kidney’s nephrons equally (Walker, Mojares, & Hernández, 2018).Poly cystic Kidney Disease: Genetic and Pathogenesis