Is there a way to identify disease severity and predict disease progression in patients with ADPKD?
Several factors contribute to kidney function decline. Cyst development is a continuous process that starts in utero and continues through the patient lifetime. The Consortium of Radiologic Imaging Studies of PKD has shown that higher kidney volumes are associated with faster declines in kidney function qualifying as a prognostic biomarker. As a result, total kidney volume (TKV) has been widely used as a primary or secondary end point in clinical trials. However, TKV has limitations as a surrogate marker for disease progression and does not always predict changes in kidney function. TKV is particularly inaccurate in patients with few large cysts or in patients with kidney atrophy secondary to ischemia or urinary tract obstruction. Furthermore, a higher TKV at an earlier age probably indicates a faster kidney growth rate. An imaging classification of ADPKD has been developed to identify patients with various degrees of disease severity and risks for progression to guide in the selection of patients for clinical trials or patients likely to benefit from effective therapies directed to slowing kidney growth. This classification uses CT and MR images and prespecified findings to assign patients as:
- • Class 1: typical, bilateral diffuse presentation
- • Class 1 is further divided into A to E based on height-adjusted TKV and age.
- • Risk for declining GFR and ESKD increased progressively from class A to class E
Classification of Autosomal Dominant Polycystic Kidney Disease Patients by Prespecified Imaging Findings
Reproduced from Irazabal, M. V., Rangel, L. J., Bergstralh, E. J., Osborn, S. L., Harmon, A. J., Sundsbak, J. L., . . . CRISP Investigators. (2015). Imaging classification of autosomal dominant polycystic kidney disease: A simple model for selecting patients for clinical trials. Journal of the American Society of Nephrology, 26 (1), 160–172 with permission of the Journal of the American Society of Nephrology.
| CLASS | SUBCLASS | TERM | DESCRIPTION |
|---|---|---|---|
| 1 Typical ADPKD | Bilateral and diffuse distribution, with mild, moderate, or severe replacement of kidney tissue by cysts, where all cysts contribute similarly to TKV. | ||
| 2 Atypical ADPKD | A | Unilateral | Diffuse cystic involvement of one kidney causing marked kidney enlargement with a normal contralateral kidney defined by a normal kidney volume (<275 mL in men; <244 mL in women) and having no or only 1–2 cysts. |
| Segmental | Cystic disease involving only one pole of one or both kidneys and sparing the remaining kidney tissue. | ||
| Asymmetric | Diffuse cystic involvement of one kidney causing marked kidney enlargement with mild segmental or minimal diffuse involvement of the contralateral kidney defined by a small number of cysts (i > 2 but <10) and volume accounting for <30% of total kidney volume. | ||
| Lopsided | Bilateral distribution of kidney cysts with mild replacement of kidney tissue with atypical cysts where five cysts or less account for at least 50% TKV. | ||
| B | Bilateral presentation with acquired unilateral atrophy | Diffuse cystic involvement of one kidney causing mod-severe kidney enlargement with contralateral acquired atrophy. (The largest cyst diameter is used to estimate individual cyst volume). | |
| Bilateral presentation with bilateral kidney atrophy | Impaired kidney function (SCr ≥ 1.5 mg/dL) without significant enlargement of the kidneys, defined by an average length <14.5 cm, and replacement of kidney tissue by cysts with atrophy of the parenchyma. |
ADPKD , Autosomal dominant polycystic kidney disease; TKV, total kidney volume.
Class 2 includes patients who present with unilateral, segmental, asymmetric, or bilateral atypical presentation (class 2A) but also patients who present with bilateral distribution with acquired unilateral atrophy or bilateral kidney atrophy (class 2B). Patients qualifying as class 2A presented low risk for estimated glomerular filtration rate (eGFR) decline, and patients classified as 2B may not benefit from therapies directed to slowing kidney growth. For prognostic enrichment design in randomized clinical trials, it was proposed to exclude class 1A and 2 and to follow class 1B patients to more precisely define their risk for progression. An online tool to estimate height-adjusted total kidney volume and classify patients with typical ADPKD is available ( http://www.mayo.edu/research/documents/pkd-center-adpkd-classification/doc-20094754 ).
