Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP)

General Description

The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) was established to develop and implement studies to test whether imaging techniques can provide accurate and reproducible markers of progression of renal disease in patients with polycystic kidney disease. Autosomal-dominant polycystic kidney disease (ADPKD) is characterized by gradual renal enlargement and cyst growth prior to loss of renal function; however, standard radiographic imaging has not provided the resolution and accuracy necessary to detect small changes in renal volume or to reliably measure renal cyst volumes. The CRISP cohort study longitudinally observed ADPKD individuals using high-resolution magnetic resonance (MR) imaging to determine if change in renal and cyst volumes can be detected over a short period of time, and if they correlate with decline in renal function early in disease.

Patients who were diagnosed with ADPKD and had a creatinine clearance of at least 70 mL/min were enrolled. Standardization studies were conducted at each participating clinical center. After, in the full-scale protocol, participants underwent standardized MR renal imaging, comprehensive clinical evaluation, evaluation of renal iothalamate clearance, and determination of 24-hour urinary albumin and electrolyte excretion. Stereology was used from T1-weighted images to quantify renal volume, and region-growing thresholding was used from T2-weighted images to determine cyst volume.

The CRISP cohort was also analyzed by molecular analysis. Given the high level of unclassified variants (UCV) in patients with ADPKD, the purpose of the molecular analysis was to systematically classify UCVs in the PKD1 and PKD2 genes.

The current data package contains data through the CRISP 3 cycle as well as CRISP allele frequency data.

MRI images for CRISP participants are not included in the package, but are available upon request.

Objectives

The primary goal of the CRISP study group was to make prospective, longitudinal measurements of cyst and kidney growth in a large cohort of patients with ADPKD.

The objective of the mutation-based molecular analysis was to screen and evaluate UCVs in the ADPKD population.

Outcome Measure

Increased renal volume, cyst volume, and % cyst volume were primary endpoints of the study. Changes in glomerular filtration rate (GFR), serum creatinine level, the reciprocal of serum creatinine, and blood urea nitrogen between baseline and termination of the study were also measured.

The outcome measure of the molecular analysis was UCVs in the PKD1 and PKD2 genes.

Criteria

The study enrolled participants ages 15 to 46 years who met the following criteria:

• Diagnosis of ADPKD
• Actual or estimated creatinine clearance of at least 70 mL/min
• Serum creatinine level of ≤ 1.6 mg/deciliter for men and ≤ 1.4 mg/deciliter for women

Patients were ineligible if they had other medical conditions besides hypertension that could affect renal function (e.g., diabetes mellitus).

Outcome

The study showed that MR measures of renal and cyst volume are reliable and accurate in patients with ADPKD. Findings indicated that renal-cyst and kidney enlargement is a continuous process in most patients with ADPKD and that the kidneys behaved as though the cysts within them enlarged at a steady rate specific to the patient.

Results showed a strong relationship between kidney volume at the beginning of the study and the subsequent change in the GFR, which provides support for the view that enlarging cysts have an important role in promoting the ultimate decline in GFR and renal function.

In the molecular analysis of the CRISP cohort, mutations were identified in 180 probands, of which 153 were in PKD1 and 27 were in PKD2, and 30% of the mutations were recurrent. These results demonstrate the potential for molecular diagnostics in ADPKD.