Clinical Guidance

PKD1

Source: GeneReviews — "Polycystic Kidney Disease, Autosomal Dominant"

Penetrance

Penetrance in ADPKD is age and genotype dependent. The penetrance of multiple bilateral kidney cysts in older adults is close to 100%. However, because the disease is progressive, few cysts may be evident during childhood or young adulthood, especially in individuals with nontruncating PKD1 pathogenic variants, pathogenic variants in PKD2, or a pathogenic variant in another ADPKD-related gene.

Source: GeneReviews — "Polycystic Kidney Disease, Autosomal Dominant"

Diagnostic Criteria

Diagnostic criteria for autosomal dominant polycystic kidney disease (ADPKD) are discussed in the executive summary of the KDIGO Controversies Conference . Suggestive Findings ADPKD should be suspected in individuals with the following: • Multiple bilateral kidney cysts and absence of manifestations suggestive of a different cystic kidney disease • Cysts in other organs, especially the liver, but also seminal vesicles, pancreas, and arachnoid membrane • Enlargement of the kidneys or liver on physical examination • Hypertension in an individual younger than age 35 years • An intracranial aneurysm • Family history consistent with autosomal dominant inheritance (e.g., affected males and females in multiple generations). Absence of a known family history does not preclude the diagnosis. Establishing the Diagnosis The diagnosis of ADPKD is established in a proband with ANY of the following: • and an affected first-degree relative with ADPKD • and an affected first-degree relative with ADPKD • in one of the genes listed in Age-Specific Ultrasound Criteria Age-specific ultrasound criteria in an individual with an affected first-degree relative : • The presence of three or more (unilateral or bilateral) kidney cysts in an individual age 15-39 years • The presence of two or more cysts in each kidney in an individual age 40-59 years • Large echogenic kidneys without distinct macroscopic cysts in an infant/child at 50% risk for ADPKD Note: (1) The positive predictive value of these criteria is described as 100%, if (a) the disorder is PKD1- or PKD2-related ADPKD and (b) the individual is age 15-59 years at the time of evaluation . Note that there are other genetic causes of kidney cysts in addition to fully penetrant pathogenic variants in PKD1 or PKD2 (see , , and ). (2) The sensitivity of ultrasound criteria is decreased in families with a pathogenic variant in PKD2, families with incompletely penetrant nontruncating PKD1 pathogenic variants, and families with pathogenic variants in less commonly associated genes. In these situations, a significant number of affected individuals may not be diagnosed using these criteria, which may pose a problem when exclusion of the diagnosis is necessary to identify potential related kidney donors . Table 1. Ultrasound Criteria for Diagnosis of ADPKD in Individuals at 50% Risk for ADPKD Based on Family History

Source: GeneReviews — "Polycystic Kidney Disease, Autosomal Dominant"

Differential Diagnosis

In the absence of a family history of polycystic kidney disease and/or in the presence of atypical presentations, benign simple cysts and other cystic diseases should be considered in the differential diagnosis. Studies of potential kidney donors using contrast-enhanced CT, which detects smaller cysts (1-2 mm), showed that from age 19 to 49 years, 39%, 22%, 7.9%, and 1.6% had at least one cyst ≥2 mm, ≥5 mm, ≥10 mm, and ≥20 mm in diameter, respectively, while from age 50 to 75 years, 63%, 43%, 22%, and 7.8% had at least one cyst ≥2 mm, ≥5 mm, ≥10 mm, and ≥20 mm in diameter, respectively . Genetic disorders in the differential diagnosis of autosomal dominant polycystic kidney disease (ADPKD) are summarized in ; acquired conditions in the differential diagnosis are summarized in . Table 5a. Genetic Disorders in the Differential Diagnosis of ADPKD

Management Guidelines

Treatment guidelines formulated at the autosomal dominant polycystic kidney disease (ADPKD) KDIGO conference are summarized in . Evaluations Following Initial Diagnosis To establish the extent of disease and needs of an individual diagnosed with ADPKD, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 6. Recommended Evaluations Following Initial Diagnosis in Individuals with ADPKD

Source: GeneReviews — "Polycystic Kidney Disease, Autosomal Dominant"

Clinical Guidance

Avoid the following:

• Long-term administration of nephrotoxic agents (e.g., combination analgesics, NSAIDs)

• Caffeine in large amounts. There is no evidence that low or moderate use of caffeinated beverages accelerates the progression of ADPKD.

• High-salt diet, smoking, and obesity

• Use of estrogens and possibly progestogens in individuals with severe polycystic liver disease

Source: GeneReviews — "Polycystic Kidney Disease, Autosomal Dominant"

Therapies Under Investigation

Significant advances in the understanding of the genetics of ADPKD and the mechanisms of cyst growth have revealed additional likely targets for therapeutic intervention. Somatostatin analogs. Octreotide, a long-acting form of somatostatin, has been shown to slow the enlargement of polycystic kidneys and livers in an animal model of PKD and of polycystic kidneys and liver in a small randomized, placebo-controlled, crossover study . Two randomized, placebo-controlled trials of octreotide and lanreotide for polycystic kidney and liver disease have shown that the administration of these somatostatin analogs causes a moderate but significant reduction in liver volume and decreases the growth velocity of polycystic kidneys compared to placebo .

Source: GeneReviews — "Polycystic Kidney Disease, Autosomal Dominant"

Surveillance Guidelines

Guidance on surveillance is available in . Table 7. Recommended Surveillance for Individuals with ADPKD

Source: GeneReviews — "Polycystic Kidney Disease, Autosomal Dominant"