Concentrations of the phosphate-regulating hormone fibroblast growth factor-23 (FGF-23) are elevated in patients with chronic kidney disease (CKD), but whether higher plasma FGF-23 concentrations associate with all-cause mortality, cardiovascular events, or initiation of chronic dialysis is not completely understood. Here, we measured FGF-23 concentration in stored plasma samples from 1099 patients with advanced CKD who participated in The Homocysteine in Kidney and End Stage Renal Disease study. Mean serum phosphorus concentration was 4.3 mg/dl, median FGF-23 concentration was 392 RU/ml, and mean GFR was 18 ml/min/1.73 m 2 . During a median follow-up of 2.9 yr, 453 (41%) patients died from any cause, 215 (20%) had a cardiovascular event, and 615 (56%) initiated chronic dialysis. Compared with the lowest quartile of FGF-23, each subsequent quartile associated with a progressively higher risk for death, adjusted for confounders (HR [95% CI] of 1.24 [0.91 to 1.69], 1.76 [1.28 to 2.44], and 2.17 [1.56 to 3.08] for the second through fourth quartiles, respectively). In addition, compared with the lowest quartile, the two highest quartiles of FGF-23 also associated with a significantly elevated risk for cardiovascular events and initiation of chronic dialysis. In conclusion, in advanced CKD, FGF-23 strongly and independently associates with all-cause mortality, cardiovascular events, and initiation of chronic dialysis.

Purpose PSA and free PSA (fPSA) have limited specificity for detecting clinically significant, curable prostate cancer (PCa), leading to unnecessary biopsies and detection and treatment of some indolent tumors. [−2]proPSA (p2PSA) may improve specificity for detecting clinically significant PCa. Our objective was to evaluate p2PSA, fPSA, and PSA in a mathematical formula (prostate health index [phi] = [−2]proPSA / fPSA) × PSA1/2) to enhance specificity for detecting overall and high-grade PCa. Materials and Methods We enrolled 892 men in a prospective multi-institutional trial with no history of PCa, normal rectal examination, a PSA of 2–10 ng/mL, and ≥6- core prostate biopsy. We examined the relationship of serum PSA, %fPSA and phi with biopsy results. The primary endpoints were the specificity and AUC using phi to detect overall and Gleason ≥7 prostate cancer on biopsy compared with %fPSA. Results For the 2–10 ng/mL PSA range, at 80–95% sensitivity, the specificity and AUC (0.703) of phi exceeded those of PSA and %fPSA. Increasing phi was associated with a 4.7-fold increased risk of PCa and 1.61-fold increased risk of Gleason ≥7 disease on biopsy. The AUC for phi (0.724) exceeded that of %fPSA (0.670) in discriminating between PCa with Gleason ≥ 4+3 vs. lower grade disease or negative biopsies. Phi results were not associated with age and prostate volume. Conclusions Phi may be useful in PCa screening to reduce unnecessary biopsies in men age ≥50 years with PSA 2–10 ng/mL and negative DRE, with minimal loss in sensitivity.

BackgroundAbout half of Americans 50 to 75 years old do not follow recommended colorectal cancer (CRC) screening guidelines, leaving 40 million individuals unscreened. A simple blood test would increase screening compliance, promoting early detection and better patient outcomes. The objective of this study is to demonstrate the performance of an improved sensitivity blood-based Septin 9 (SEPT9) methylated DNA test for colorectal cancer. Study variables include clinical stage, tumor location and histologic grade.MethodsPlasma samples were collected from 50 untreated CRC patients at 3 institutions; 94 control samples were collected at 4 US institutions; samples were collected from 300 colonoscopy patients at 1 US clinic prior to endoscopy. SEPT9 methylated DNA concentration was tested in analytical specimens, plasma of known CRC cases, healthy control subjects, and plasma collected from colonoscopy patients.ResultsThe improved SEPT9 methylated DNA test was more sensitive than previously described methods; the test had an overall sensitivity for CRC of 90% (95% CI, 77.4% to 96.3%) and specificity of 88% (95% CI, 79.6% to 93.7%), detecting CRC in patients of all stages. For early stage cancer (I and II) the test was 87% (95% CI, 71.1% to 95.1%) sensitive. The test identified CRC from all regions, including proximal colon (for example, the cecum) and had a 12% false-positive rate. In a small prospective study, the SEPT9 test detected 12% of adenomas with a false-positive rate of 3%.ConclusionsA sensitive blood-based CRC screening test using the SEPT9 biomarker specifically detects a majority of CRCs of all stages and colorectal locations. The test could be offered to individuals of average risk for CRC who are unwilling or unable to undergo colonscopy.