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PATIENT STORY

A 43-year-old woman with newly diagnosed hypertension reports persistent bilateral flank pain. She has a family history of "kidney problems." On urinalysis, she is noted to have microscopic hematuria. An ultrasound and abdominal computed tomography (CT) scan show bilateral polycystic kidneys (Figure 72-1).

FIGURE 72-1

Polycystic kidneys in a 43-year-old woman with hematuria. (Reproduced with permission from Michael Freckleton, MD.)

INTRODUCTION

Polycystic kidney disease (PKD) is a manifestation of a group of inherited disorders resulting in renal cyst development. In the most common form, autosomal-dominant polycystic kidney disease (ADPKD), extensive epithelium-lined cysts develop in the kidney; in some cases, abnormalities also occur in the liver, pancreas, brain, arterial blood vessels, or a combination of these sites.

EPIDEMIOLOGY

  • Most common tubular disorder of the kidney, affecting 1 in 339 to 1 in 492 individuals, based on autopsy studies.1

  • Autosomal dominant in 80% to 85% of cases, rarely as an autosomal recessive trait.1

  • ADPKD accounts for approximately 4.7% of cases of end-stage renal disease (ESRD).2

  • Most frequently seen in the third and fourth decades of life, but can be diagnosed at any age.

  • Very early-onset ADPKD (under 2 years of age) occurs in only 1% to 2% of affected children.1

ETIOLOGY AND PATHOPHYSIOLOGY

  • ADPKD results from mutations in either of 2 genes that encode plasma membrane–spanning polycystin 1 (PKD1) and polycystin 2 (PKD2).3 Polycystins regulate tubular and vascular development in the kidneys and other organs (liver, brain, heart, and pancreas). PKD1 and PKD2 are colocalized in primary cilia and appear to mediate Ca2+ signaling as a mechanosensor, essential for maintaining the differentiated state of epithelia lining tubules in the kidney and biliary tract.4 These mutations result in many abnormalities including increased proliferation and apoptosis and loss of differentiation and polarity.5

  • Almost universally associated with different forms of cystic kidney disease is activation of the mammalian target of rapamycin (mTOR) pathway, a protein kinase complex that promotes anabolic programs in response to nutrients, growth factors, and cellular energy levels.1

  • Macrophages infiltrate kidney cysts in patients with ADPKD. Macrophage migration inhibitory factor accumulates in cyst fluid of ADPKD kidneys and likely promotes cystic epithelial cell proliferation by activating mTOR and other pathways.6

  • Few (1% to 5%) nephrons develop cysts.

  • Remaining renal parenchyma shows varying degrees of tubular atrophy, interstitial fibrosis, and nephrosclerosis.

  • Cysts are also found in other organs such as liver (Figure 72-2), spleen, pancreas, and ovaries. Liver cysts are found in up to 80% of patients with ADPKD.3 There is also an increased incidence of intracranial aneurysms (5% to 12%).

  • Autosomal-recessive PKD (ARPKD) is the neonatal form of PKD that is associated with enlarged kidneys and biliary dysgenesis.4 The ...

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