Christopher M. Moon, Laura Gunder, DHSc, MHE, PA-C, and Ami R. Steele, MMSc, PA-C
June 06 2011
At a glance
■Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of chronic kidney disease.
■Patients may present with flank or abdominal pain, cystitis secondary to UTI, hematuria and headaches.
■There is no proven treatment available that will prevent or delay the progression of ADPKD.
■About 50% of ADPKD patients will require a dialysis or a renal transplant by the age of 60 years.
Autosomal dominant polycystic kidney disease (ADPKD), also referred to as adult PKD, is the most common genetic cause of chronic renal disease.1 Among all hereditary diseases, ADPKD is 20 times more common than Huntington's chorea, 15 times more common than cystic fibrosis, and 10 times more common than sickle cell disease.2 As research continues, the understanding of the mechanisms of the disease has led to an increase in clinical trials available to patients. Many of these trials show promise in preventing cyst formation, which is the underlying cause of renal failure attributable to ADPKD.
A comprehensive understanding of the disease process will enable providers to accurately diagnose and manage patients with this condition. While there is currently no approved cure for the disease,3 it is crucial for clinicians to update their knowledge on the topic as new information is discovered and new treatments are made available. It is the role of the primary-care provider to manage patients' overall health and offer prompt treatment of complications as well as referral to a nephrologist when appropriate.
Prevalence and epidemiology
ADPKD has an estimated prevalence of one case in every 500 people, affecting approximately 600,000 Americans and as many as four to six million people worldwide.4 As the most common inherited disorder of the kidneys in humans, ADPKD afflicts approximately 10% of the patient population with end stage renal disease (ESRD).2
ADPKD is considered a systemic disorder and results from mutations in either the PKD1 or PKD2 gene.5 The PKD1 gene is found on the short arm of chromosome 16, while the PKD2 gene is found on chromosome 4. The prevalence is 85%-90% having the PKD1 mutation, with the remaining 10%-15% having the PKD2 mutation.6
The PKD1 gene encodes for polcystin-1, a large receptor-like molecule. The PKD2 gene encodes for polycytin-2, which acts like an ion channel protein. Both polcystin-1 and 2 are transmembrane proteins that are present in all segments of nephrin, a protein necessary for proper function of the renal filtration barrier, and are involved with the slit diaphragm. It is not certain whether the proteins act together or independently to carry out their functions. They are thought to regulate epithelial cell gene transcription, differentiation, apoptosis, and cell matrix interactions. Improper functioning of these proteins leads to epithelial differentiation, uncontrolled proliferation, apoptosis, altered cell polarity, disorganized surrounding extracellular fluid, increased fluid sections, and the abnormal expression of several genes. Cyclic adenosine monophosphate levels increase and are thought to be secondary to vasopressin stimulation. This may lead to cystogenesis by causing an increase in cell proliferation and fluid secretion into the cyst through aquaporin channels and chloride channels.5 When cysts enlarge, they begin to compress adjacent parenchyma, causing ischemia and occluding normal tubules. This leads to progressive impairment of renal function.7
To read more please visit http://pkdkidney.blogspot.co.uk/2011/06/adult-polycystic-kidney-disease.html
