The PREDICT study: a randomized double-blind comparison of contrast-induced nephropathy after low- or isoosmolar contrast agent exposure.

OBJECTIVE: The objective of the PREDICT (patients with renal impairment and diabetes undergoing computed tomography) study was to compare the incidence of contrast-induced nephropathy (CIN) after administration of low-osmolar (iopamidol 370, 796 mOsm/kg) or isoosmolar (iodixanol 320, 290 mOsm/kg) contrast medium in patients with diabetes and chronic kidney disease undergoing CT. SUBJECTS AND METHODS: Two hundred sixty-three patients with moderate to severe chronic kidney disease (estimated glomerular filtration rate [GFR] = 20-59 mL/min/1.73 m(2)) and diabetes mellitus were randomized to receive at least 65 mL of iopamidol 370 or iodixanol 320 for a CT procedure. Serum creatinine levels were measured at baseline and 48-72 hours after contrast administration. CIN was defined as an increase in the serum creatinine level after contrast administration of >or= 25% from the baseline level. The incidence of CIN in the total study population and the incidence of CIN in patients at increased risk for CIN were compared using Fisher's exact test. RESULTS: Two hundred forty-eight patients were included in the CIN analysis: 125 receiving iopamidol 370 and 123 receiving iodixanol 320. Study population demographics were comparable, as was baseline renal function (estimated GFR = 47.6 mL/min/1.73 m(2) for the iopamidol 370 group vs 49.9 mL/min/1.73 m(2) for the iodixanol 320 group; p = 0.16). Increases in the serum creatinine value of >or= 25% occurred in seven patients (5.6%) receiving iopamidol 370 and in six patients (4.9%) receiving iodixanol 320 (95% CI, -4.8% to 6.3%; p = 1.0). The mean serum creatinine change from the baseline level was 0.04 mg/dL in both groups (analysis of covariance, p = 0.80). In patients with a baseline serum creatinine value of >or= 2.0 mg/dL, baseline estimated GFR of 140 mL of contrast medium, the incidence of CIN was low and comparable between the two study groups (p = 1.0 in all instances). CONCLUSION: The incidence of CIN in patients with diabetes and chronic kidney disease receiving IV contrast medium was not significantly different after CT using iopamidol 370 or iodixanol 320.

miR-21-3p is a positive regulator of L1CAM in several human carcinomas.

Expression of L1 cell adhesion molecule (L1CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, ß-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application.