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INTRODUCTION

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Renal cystic disease includes a myriad of conditions characterized by the presence of multiple hereditary or acquired renal cysts, which differ in their clinical presentation, prognosis, and management. Renal cysts are composed of smooth-walled, enclosed fluid-filled circular structures that form in the kidney by focal out pouching of renal tubules. Although the mechanism underlying cyst formation remain to be fully elucidated, defects in the primary ciliary sensing mechanisms, intracellular calcium regulation, and cellular cyclic AMP (cAMP) accumulation have been shown to contribute to cyst formation in autosomal dominant and autosomal recessive polycystic kidney diseases (ADPKD and ARPKD), which represent a significant cause of morbidity and mortality in children and young adults. Currently, there are no FDA approved treatments for ADPKD, and the existing standard of care includes risk modification, management of complications, and renal replacement therapy with dialysis or organ transplantation. Several drugs designed to slow or arrest the progression of ADPKD have shown promise in preclinical models and clinical trials, including vasopressin receptor antagonists and somatostatin analogs. The vasopressin-2 receptor antagonist Tolvaptan has been the most successful drug therapy to reduce the rate of increase in total kidney volume (TKV) and ameliorate renal functional decline in patients with ADPKD. Further elucidation of the mechanisms implicated in cyst formation and development would provide impetus for correcting the underlying abnormalities in cystic pathways.

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AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

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Essentials of Diagnosis

  • Two renal cysts unilaterally or bilaterally before age 30 years by renal ultrasound in patients with a family history of ADPKD.

  • Two cysts in each kidney between the ages of 30 and 59 years by renal ultrasound in patients with a family history of ADPKD.

  • Four or more cysts in each kidney after age elder than or equal to 60 years by renal ultrasound in patients with a family history of ADPKD.

  • Genetic testing (linkage analysis and direct DNA sequencing) is available as a clinical test, and can detect PKD1 and PKD2 mutations in approximately 90% of confirmed cases.

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General Considerations

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ADPKD remains one of the most frequent monogenic disorders and one of the main causes of renal insufficiency that affects 1 in 400–1000 individuals worldwide. In the United States, approximately half million people suffer from ADPKD, which accounts for an important fraction of new patients entering dialysis programs each year.

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The disorder is transmitted in autosomal dominant pattern with varied expression, but nearly always with complete penetrance of mutated genes. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, whereas mutations in the PKD2 gene account for approximately 15% of the remaining mutation identified ADPKD cases. Between 7% and 10% of ADPKD cases remain genetically unresolved after genetic screening. Recent data suggest that mutations in GANAB, a coding gene that encodes for a glucosidase-II alpha subunit, may account for approximately 3% of the genetically unresolved ADPKD cases. However, due ...

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