Assignment 1-Polycystic Kidney Disease
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Assignment 1: Polycystic Kidney Disease
Zeleria Jackson
University of Florida
GMS 6401: Medical Renal Physiology
Jaya Kolli, M.D.
October 29, 2023
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Polycystic kidney disease (also known as PKD) is a hereditary illness characterized by the formation of many fluid-filled cysts in the kidneys (NKF, 2023; NIDDK). Unlike simple kidney cysts, which are normally benign and can occur later in life, PKD cysts can modify the structure of your kidneys, including making them considerably bigger (NIDDK). Ultimately, PKD is a variant of chronic kidney disease (CKD) that causes kidney function to decline and may eventually lead to renal failure (NIDDK). PKD affects around 600,000 people in the United States and is the fourth major cause of kidney failure (NKF, 2023). Globally, PKD affects individuals of all ages, races, and ethnicities (NKF, 2023). Additionally, the condition affects both males and females equally (NKF, 2023). The disease's autosomal dominant variant is far more frequent than its autosomal recessive version (MedlinePlus). The autosomal dominant type (ADPKD) affects 1 in 500-1,000 people, while the autosomal recessive type (ARPKD) affects 1 in 20,000-40,000 people (MedlinePlus). ADPKD is frequently referred to as "adult PKD" since symptoms typically manifest and are then
diagnosed between the ages of 30 and 50 (NIDDK; Pope, 2012). On the other hand, due to its early diagnosis, ARPKD is frequently referred to as "infantile PKD” (NIDDK).ARPKD can result in impaired kidney function in a developing child, resulting in breathing issues that endanger its survival (NIDDK). Within the first week of life, over 30% of neonates with ARPKD tragically pass (NIDDK; Guay-Woodford & Desmond, 2003).
While gene mutations account for the majority of instances of PKD, in other instances the
disease can be acquired (MedlinePlus). Renal failure and dialysis are frequently linked to acquired polycystic kidney disease (ACKD) because it can occur in kidneys that have sustained significant damage over time which resulted in extensive scarring (NKF, 2023). Approximately 90% of dialysis patients acquire ACKD after 5 years (NKF, 2023). Most often, hematuria is the
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main symptom/cause for concern in patients with ACKD (NKF, 2023). This occurs as a result of the cysts bleeding into the urinary system and discoloring the urine (NKF, 2023). The etiology of PKD is mutations in the PKD1
, PKD2
, and PKHD1
genes (MedlinePlus).
Currently, there are over 250 identified PKD1
gene mutations that contribute to 85% of ADPKD cases (
PKD1 gene
). Mutations in the PKD1
gene (located on chromosome 16) include changes to one or more base pairs (deletions or insertions) (
PKD1 gene
). An unusually tiny, nonfunctional variant of the polycystin-1 protein is expected to result from the majority of PKD1
mutations (
PKD1 gene
). While the exact mechanism by which a deficiency of polycystin-1 causes cysts is unknown, it most likely interferes with the protein's signaling role in primary cilia
and throughout the cell (
PKD1 gene
). This can cause aberrant cell growth and division in the renal tubule lining, which can result in the development of cysts (
PKD1 gene
). Similarly to PKD1 mutations, PKD2
mutations cause signaling interference between the cell, cilia, and polycystin-1 (
PKD2 gene
). These gene mutations also result in a dysfunctional variant of the polycystin-2 protein which leads to the cyst proliferation that occurs on the kidneys (
PKD2 gene
). At the moment, there have been over 75 identified PKD2
gene (located on chromosome 4)
mutations that contribute to the remaining 15% of ADPKD cases (
PKD2 gene
).
Similar PKHD1 gene mutations occur in the recessive version of PKD (ARPKD), the more severe version of the condition that generally manifests itself at birth or in early childhood (
PKHD1 gene
). Alterations of base pairs in the PKHD1 gene (located on chromosome 6) result in the fibrocystin protein being either produced in an abnormally tiny, nonfunctional form or its normal structure and function are disrupted (
PKHD1 gene
). Nonetheless, these irregularities manifest into cysts that strip the kidneys of their essential functions (
PKHD1 gene
). Surprisingly
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enough, there have been over 270 PKHD1 gene mutations found in ARPKD patients (
PKHD1 gene
).
Even among members of the same family, the severity of PKD differs from person to person (Mayo Clinic, 2022). People with PKD frequently attain end-stage renal disease between the ages of 55 and 65 (Mayo Clinic, 2022). However, some persons with PKD have a moderate condition and may never reach end-stage renal disease (Mayo Clinic, 2022). Usually, ADPKD does not manifest itself until your kidney cysts are half an inch or more in size (NIDDK). Pain (typically caused by cyst development, infection, or bleeding/bursting), elevated blood pressure, and renal failure are all common symptoms of ADPKD (NIDDK). Death and a coma may result from untreated renal failure (NIDDK). Unfortunately, kidney failure develops in about half of ADPKD patients by the age of 70 (NIDDK; Torres & Grantham, 2011). Hematuria, back and rib discomfort, and headaches are other typical symptoms (NIDDK). Not only may problems from ADPKD harm your kidneys, but also other systems in your body (NIDDK). There can be immediate difficulties with ADPKD or some that exhibit with time depending on whether you carry the PKD1 or PKD2 gene, further issues may not arise for many years (NIDDK). The vascular system (abnormal heart valves, brain aneurysms), digestive system (liver cysts, pancreatic cysts, diverticula), urinary tract (UTIs, kidney stones), and reproductive system (preeclampsia) are among the issues associated with ADPKD (NIDDK).
In the womb, growth failure, an enlarged kidney, and low levels of amniotic fluid are early indicators of ARPKD (NIDDK). Other times, symptoms exhibit later in infancy or even further into adulthood (NIDDK). Nevertheless, if an ARPKD baby survives delivery, their breathing may be hampered by kidney and liver issues (NIDDK). Other complications of
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ARPKD include high blood pressure (Guay-Woodford & Desmond, 2003), which further increases a child’s likelihood of suffering from heart disease and stroke (NIDDK).
PKD currently has no known cure (NKF, 2023). In patients with PKD, a variety of supportive therapies can be used to manage symptoms, aid in slowing the formation of cysts, and
stop or delay the loss of kidney function (NKF, 2023). In recent years (April of 2018), the FDA permitted the use of tolvaptan (NKF, 2023), a novel medication that inhibits the formation of kidney cysts (Mayo Clinic, 2022). Other proactive treatment options include using ARBs and ACE inhibitors for high blood pressure; following a healthy diet and drinking water can support declining kidney function; OTC pain medications can be used to treat discomfort; antibiotics are used to promptly treat kidney infections; dialysis and kidney transplants are available to patients with kidney failure; and surgical and nonsurgical treatments are available for PKD patients with aneurysms (Mayo Clinic, 2022).
As for patients with ARPKD, an enlarged kidney can only be removed once breathing complications arise (some children require dialysis or a transplant); growth failure can be treated with nutritional therapy or human growth hormone (in severe cases); infants with breathing problems are treated with artificial ventilation; kidney failure is treated with either peritoneal dialysis or hemodialysis; liver problems require transplants; and lastly, high blood pressure is combated with medication (NIDDK).
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References
Guay-Woodford LM, Desmond RA. (2003). Autosomal recessive polycystic kidney disease: the clinical experience in North America.
Pediatrics
:
111(5 Pt 1):1072–1080.
Mayo Foundation for Medical Education and Research. (2022, November 24). Polycystic kidney disease
. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/polycystic-kidney-
disease/diagnosis-treatment/drc-20352825 Polycystic kidney disease
. National Kidney Foundation. (2023, June 29). https://www.kidney.org/atoz/content/polycystic Pope JC. (2012). Renal dysgenesis and cystic disease of the kidney. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, Novick AC, eds.
Campbell-Walsh Urology.
10th ed. Philadelphia, PA: Elsevier Saunders: 118e1–118e46.
Torres VE, Grantham JJ. (2011). Cystic diseases of the kidney. In: Taal MW, Chertow GM, Marsden PA, Skorecki K, Alan SL, Brenner BM, eds.
Brenner and Rector’s the Kidney.
9th ed. Philadelphia, PA: Elsevier Saunders: 1626–1667.
U.S. Department of Health and Human Services. (n.d.). What is Polycystic Kidney Disease? -
NIDDK
. National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/
what-is-pkd U.S. National Library of Medicine. (n.d.-a). PKD1 gene: Medlineplus Genetics
. MedlinePlus. https://medlineplus.gov/genetics/gene/pkd1/
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U.S. National Library of Medicine. (n.d.-b). PKD2 gene: Medlineplus Genetics
. MedlinePlus. https://medlineplus.gov/genetics/gene/pkd2/ U.S. National Library of Medicine. (n.d.-c). PKHD1 gene: Medlineplus Genetics
. MedlinePlus. https://medlineplus.gov/genetics/gene/pkhd1/ U.S. National Library of Medicine. (n.d.-d). Polycystic kidney disease: Medlineplus Genetics
. MedlinePlus. https://medlineplus.gov/genetics/condition/polycystic-kidney-disease/