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[Dr. Shapiro] This is Dr. Samantha Shapiro, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest trusted content from the best minds in medicine. And now onto the episode.
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[Dr. Handy] Hi everyone, welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy.
[Dr. Wiener] And I'm Dr. Charlie Wiener, and we're joining you from the Johns Hopkins School of Medicine.
[Dr. Handy] Welcome to episode 111, a 24-year-old with pelvic pain.
[Dr. Wiener] Cathy, today we're seeing a new patient in clinic, she's 24 years old and was recently evaluated in the emergency department for pelvic pain. Her urinalysis, pregnancy test, and pelvic examinations were unremarkable, but an ultrasound demonstrated two renal cysts in each of her kidneys. She does not know her family history because she was adopted at birth and has never sought out her biologic parents. The pelvic pain is resolved and her physical examination is normal. The question asks, in discussing her situation, all of the following statements are true except: A. one of her biologic parents likely has similar findings; B. she's at risk for end-stage renal disease; C. she's at risk of uric acid kidney stones; D. she's at risk of developing hypertension; and E. she should receive annual screening for intracerebral aneurysms.
[Dr. Handy] All right, I see where we're going with this. So first, in thinking about the diagnosis that she has and then later what it's associated with. So first, it's not normal for someone that young to have four renal cysts. A family history would be helpful, but I suspect that she has polycystic kidney disease.
[Dr. Wiener] How would the family history be helpful?
[Dr. Handy] Well, let's start with the polycystic kidney disease, so the autosomal dominant form, so-called ADPKD, is the most common life-threatening monogenetic disorder worldwide and affects over 10 million individuals. Pathophysiologically, it's one of the ciliopathies or disorders of primary cilia, which often cause renal cysts because of the dysfunction in the renal tubules. Diagnostically, if a patient is at risk due to a known family history, and someone this age demonstrating the presence of at least two renal cysts, which can be either unilateral or bilateral, well, that's sufficient for diagnosis with a sensitivity value of 96% and specificity of 100%. Because the development of cysts increases with age, the threshold for the number of cysts increases with age. Also, if you suspect a patient over 30 years old of having ADPKD, the absence of at least two cysts in each kidney is associated with a false negative rate of 0% and can be used for disease exclusion.
[Dr. Wiener] Okay, so it sounds like this patient, you suspect she likely has ADPKD. Is there a genetic test that may be definitive?
[Dr. Handy] Yes, so it's typically caused by mutations in the genes coding for polycystin-1 and polycystin-2. Genetic testing is available for ambiguous cases, but it may be costly.
[Dr. Wiener] Okay, well, let's assume that this woman does have polycystic kidney disease and let's get back to the question. It's asking for the single wrong answer. So I assume that option A. is correct that probably one of her biologic parents has the disorder.
[Dr. Handy] Yeah, as the name tells us, it's transmitted in an autosomal dominant fashion, so one of her biologic parents likely has the disease.
[Dr. Wiener] Okay, well, what about the other options? Let's go through those then.
[Dr. Handy] All right, I'm going to go out of order a little bit. So despite the growth of renal cysts and having enlarged kidneys, many patients are asymptomatic into their 30s and 40s, but hypertension is a common finding and often precipitates the diagnosis. Back or flank pain is also common and that typically leads to imaging that leads to the diagnosis.
[Dr. Wiener] Okay, so that means that option D. is correct. She is at risk of developing hypertension. What about the stones, the end-stage renal disease, and the intracerebral aneurysms then?
[Dr. Handy] So these patients are most definitely at risk for nephrolithiasis, and interestingly, they're more likely than the general public to have uric acid stones. Remember, in the general public, the most common renal stones are calcium oxalate and patients with ADPKD are at long-term risk of end-stage renal disease. Now, the progression to end-stage renal disease does have notable inter and intrafamilial variability, but end-stage renal disease typically occurs in late middle age, and risk factors include an early diagnosis of polycystic kidney disease, hypertension, gross hematuria, multiple pregnancies and large kidney size.
[Dr. Wiener] Okay, so now we know that options A. through D. are true, and that leaves us with option E. screening for intracerebral aneurysm as false; but I thought patients with ADPKD are at risk for aneurysms and subarachnoid hemorrhages?
[Dr. Handy] Yeah, so this merits more discussion. So intracranial aneurysm occurs four to five times more frequently in these patients than in the general population and causes a high mortality. A family history of intracranial aneurysm is a risk factor for aneurysm rupture in ADPKD, whether hypertension and cigarette smoking are independent risk factors is not clear. About 20 to 50% of patients may experience warning headaches preceding the index episode of subarachnoid hemorrhage due to a ruptured ICA.
[Dr. Wiener] So what about screening?
[Dr. Handy] Well, the role of radiologic screening for ICA in asymptomatic patients with polycystic kidney disease remains unclear, so that's why I said that option E. is not absolutely true. That being said, patients with a positive family history of ICAs may undergo presymptomatic screening by MR angiography. Honestly, this seems like an area for more research given the potentially devastating results of a subarachnoid hemorrhage.
[Dr. Wiener] Since this is a genetic disease of the epithelium, you mentioned ciliopathies. I assume there are other potential manifestations.
[Dr. Handy] Yeah, they often also have liver cysts. They can have cardiac valvular abnormalities, such as mitral valve prolapse, and also colonic diverticula, and abdominal wall hernias.
[Dr. Wiener] Let's finish with treatment. Anything specific?
[Dr. Handy] Not yet, the most important thing is rigorous blood pressure control, which has been shown to slow cyst growth, and there are also trials of inhibiting cell proliferation or fluid secretion, but these are not yet in common uses.
[Dr. Wiener] Okay, so the teaching points in this case are that the polycystic kidney disease, of which autosomal dominant polycystic kidney disease is one, are ciliopathies characterized by epithelial disorder. It is not normal for young people to have multiple renal cysts, so screening by ultrasound can be definitive and can be diagnostic in these patients. And patients who have polycystic kidney disease are at risk for a variety of systemic illnesses and the eventual development of end-stage renal disease.
[Dr. Handy] And you can learn more about this in the Harrison's chapter on polycystic kidney disease and other inherited disorders of tubule growth and development.
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