Imaging-based diagnosis of autosomal dominant polycystic kidney disease

Abstract

The clinical use of conventional ultrasonography (US) in autosomal dominant polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic sensitivity, especially in at-risk subjects younger than 30 years of age. In this single-center prospective study, we compared the diagnostic performance of MRI with that of high-resolution (HR) US in 126 subjects ages 16-40 years born with a 50% risk of ADPKD who underwent both these renal imaging studies and comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control subjects without a family history of ADPKD completed the same imaging protocol. We analyzed 110 at-risk subjects whose disease status was unequivocally defined by molecular testing and 45 unaffected healthy control subjects. Using a total of >10 cysts as a test criterion in subjects younger than 30 years of age, we found that MRI provided both a sensitivity and specificity of 100%. Comparison of our results from HR US with those from a previous study of conventional US using the test criterion of a total of three or more cysts found a higher diagnostic sensitivity (approximately 97% versus approximately 82%) with a slightly decreased specificity (approximately 98% versus 100%) in this study. Similar results were obtained in test subjects between the ages of 30 and 40 years old. These results suggest that MRI is highly sensitive and specific for diagnosis of ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is both center- and operator-dependent.

Keywords: autosomal dominant polycystic kidney disease; clinical epidemiology; polycystic kidney disease.

Figure 1.

Study subject recruitment and exclusion. Flow diagram detailing the number of at-risk and age-matched control subjects recruited, excluded, and analyzed in the study.

Figure 2.

Distribution of total cyst counts by disease status and imaging modality. *TOR190.1 is a genetically affected subject with a body mass index of 35.6 kg/m² who had >20 renal cysts by MRI but no cyst detectable by a suboptimal US. **TOR404.1 and TOR208.5 were both unaffected but had three renal cysts by US. ^#TOR31.2 is a subject with 6 renal cysts on US and 10 renal cysts on MRI; he did not carry the familial PKD2 mutation and was considered as unaffected.

Figure 3.

Comparison of total cyst counts by US and MRI. There was a high degree of concordance of renal cyst counts by US and MRI in both at-risk subjects and healthy controls. *TOR190.1 is a genetically affected subject with >20 renal cysts by MRI but no cyst detectable by a suboptimal US. **TOR404.1 and TOR208.5 both were genetically unaffected but had three renal cysts by US. ^#TOR31.2 is genetically unaffected with 6 cysts on US and 10 cysts on MRI.

Figure 4.

Examples of small renal cysts identified by HR US and MRI. (A and B) Detection of a small (approximately 2.5 mm) cortical renal cyst by HR US and MRI in two different test subjects (denoted by arrows in A and B).