Polycystic Kidney Disease: What's Your ADPKD IQ?

Polycystic kidney disease is a common genetic disorder, affecting approximately 500 000 individuals in the US.¹ The most common form is autosomal dominant polycystic kidney disease (ADPKD), which is characterized by progressive loss of kidney function, and often, end-stage renal disease (ESRD) later in life. In this quiz, test your knowledge of ADPKD epidemiology, genetics, diagnosis, treatment, and more.

1. Based on current estimates, ADPKD affects up to how many individuals worldwide?

A. 1 in 40
B. 1 in 400
C. 1 in 4000
D. 1 in 40 000

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Answer: B. 1 in 400. ADPKD, which is usually diagnosed in adulthood, affects 1 in every 400 to 1000 people worldwide, by various estimates. Autosomal recessive polycystic kidney disease, usually diagnosed before or shortly after birth, affects 1 in 20 000 children.¹

2. ADPKD is most commonly linked to mutations in which gene?

A.PKD1B. PKD2C. GANABD. DNAJB11

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Answer: A. PKD1. Nearly 80% of ADPKD cases are related to mutations in PDK1 followed by 15% that are related to PDK2, the genes most commonly associated with ADPKD. PDK1 encodes polycystin-1 (PC1) and PDK2 encodes polycystin-2 (PC2); research suggests that PC1 and PC2 inhibit cystogenesis, and that cystogenesis occurs when PC1 and PC2 fall below a certain threshold.²

3. Approximately how many different mutations have been identified for PKD1?

A. 325
B. 750
C. 1500
D. 3000

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Answer: C. 1500. The ADPKD mutation database now includes >1500 mutations of PKD1, followed by >250 mutations of PKD2. This reflects the disease’s genetic complexity, which in the past has been a hindrance to routine genetic testing. Now, however, next-generation sequencing panels screening for PDK1, PDK2, and other cystic disease genes are available and increasingly used in both private and academic laboratories, with costs likely to decrease over time.³

4. What is the preferred initial approach to diagnosing ADPKD?

A. Ultrasound
B. Magnetic resonance imaging (MRI)
C. Computed tomography (CT) with contrast
D. Magnetic resonance angiography

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Answer: A. Ultrasound. Ultrasound is the preferred initial approach to ADPKD diagnosis because it is non-invasive, low cost, and widely available. However, MRI and CT with contrast can also be useful in some circumstances (eg, evaluating young individuals at risk for ADPKD).²

5. Beyond the characteristic kidney cysts, >90% of patients with ADPKD aged >35 years will have cysts in which organ?

A. Pancreas
B. Liver
C. Lung
D. Adrenal gland
E. Ovaries and seminal vesicles

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Answer: B. Liver. One of the main extrarenal manifestations of ADPKD is liver cysts, which can be found in >90% of patients aged >35 years. Cysts can also develop in other organs (eg, pancreas, seminal vesicles, and ovaries) but are not usually symptomatic, so systematic screening is not warranted.²

6. Which of the following is associated with the LEAST favorable renal prognosis in patients with ADPKD?

A.PKD1 truncating mutations
B.PKD1 non-truncating mutations
C.PKD2 mutation
D.GANAB mutation

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Answer: A. PKD1 truncating mutations. Patients with PKD1 mutations that are predicted to truncate the protein have the least favorable renal prognosis with a median age of 55.6 years at ESKD vs 67.9 years for patients with non-truncating mutations. Mutations in PKD2 have a more favorable renal prognosis with a median-age at ESKD of approximately 79 years.²

7. According to experts, which of the following is the most important factor when deciding on whether to treat ADPKD with approved therapies?

A. Recurrent gross hematuria
B. Kidney pain
C. Severe hypertension
D. Risk of renal progression

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Answer: D. Risk of renal progression. Progression to kidney failure is not inevitable, especially in certain patients (eg, those with more favorable PKD2 genotype or with atypical polycystic kidney disease). In clinical practice, approved therapies should be used according to clinical trial enrollment criteria or restricted to those at risk of rapid renal progression. However, other relevant outcomes such as kidney pain, severe hypertension, or recurrent gross hematuria can figure into the treatment decision as well.³

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References:

1. What Is Polycystic Kidney Disease? National Institute of Diabetes and Digestive Kidney Diseases. https://www.niddk.nih.gov/health-information/kidney-disease/polycystic-kidney-disease/what-is-pkd. Posted January 2017. Accessed May 6, 2019. 

2. Cornec-Le Gall E, Alam A, Perrone RD. Autosomal dominant polycystic kidney disease. Lancet. 2019;393:919-935. 

3. Cornec-Le Gall E, Torres VE, Harris PC. Genetic complexity of autosomal dominant polycystic kidney and liver diseases. J Am Soc Nephrol. 2018;29:13-23.