Clinical Guidance

Kidney Manifestations

Although all individuals with autosomal dominant polycystic kidney disease (ADPKD) develop cysts within the kidneys, there is substantial variability in the severity of kidney disease and other manifestations of the disease. Less variability is observed between affected individuals from the same family, but significant intrafamilial variability still exists. Poor prognostic factors include: diagnosis before age 30 years ; first episode of hematuria before age 30 years; onset of hypertension before age 35 years ; hyperlipidemia and high body mass index ; high urine sodium excretion ; lower kidney blood flow; lower serum high-density lipoprotein cholesterol ; large total kidney volume (TKV) ; and the presence of a truncating PKD1 variant .

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"

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

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"