Urinary epidermal growth factor/monocyte chemotactic peptide 1 ratio as non-invasive predictor of Mayo clinic imaging classes in autosomal dominant polycystic kidney disease.

BACKGROUND: Age- and height-adjusted total kidney volume is currently considered the best prognosticator in patients with autosomal dominant polycystic kidney disease. We tested the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for the prediction of the Mayo Clinic Imaging Classes. METHODS: Urinary epidermal growth factor and monocyte chemotactic peptide 1 levels were measured in two independent cohorts (discovery, n = 74 and validation set, n = 177) and healthy controls (n = 59) by immunological assay. Magnetic resonance imaging parameters were used for total kidney volume calculation and the Mayo Clinic Imaging Classification defined slow (1A-1B) and fast progressors (1C-1E). Microarray and quantitative gene expression analysis were used to test epidermal growth factor and monocyte chemotactic peptide 1 gene expression. RESULTS: Baseline ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 correlated with total kidney volume adjusted for height (r = - 0.6, p < 0.001), estimated glomerular filtration rate (r = 0.69 p < 0.001), discriminated between Mayo Clinic Imaging Classes (p < 0.001), and predicted the variation of estimated glomerular filtration rate at 10 years (r = - 0.51, p < 0.001). Conditional Inference Trees identified cut-off levels of the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 for slow and fast progressors at > 132 (100% slow) and < 25.76 (89% and 86% fast, according to age), with 94% sensitivity and 66% specificity (p = 6.51E-16). Further, the ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 at baseline showed a positive correlation (p = 0.006, r = 0.36) with renal outcome (delta-estimated glomerular filtration rate per year, over a mean follow-up of 4.2 ± 1.2 years). Changes in the urinary epidermal growth factor and monocyte chemotactic peptide 1 were mirrored by gene expression levels in both human kidney cysts (epidermal growth factor: - 5.6-fold, fdr = 0.001; monocyte chemotactic peptide 1: 3.1-fold, fdr = 0.03) and Pkd1 knock-out mouse kidney (Egf: - 14.8-fold, fdr = 2.37E-20, Mcp1: 2.8-fold, fdr = 6.82E-15). CONCLUSION: The ratio of urinary epidermal growth factor and monocyte chemotactic peptide 1 is a non-invasive pathophysiological biomarker that can be used for clinical risk stratification in autosomal dominant polycystic kidney disease.

DBT-galactography: a promising tool for improving the diagnostic workup of nipple discharge.

BACKGROUND: Our aim was to compare the diagnostic performance of digital breast tomosynthesis (DBT)-galactography with that of full-field digital (FFD)-galactography for detecting intraductal breast lesions using an intra-individual design. METHODS: Forty-nine consecutive patients with spontaneous, unilateral, single-pore nipple discharge and inconclusive FFD mammography and ultrasonography underwent galactography with a "COMBO" technique combining FFD- and DBT-galactography acquisitions. Examinations were independently analysed by two breast radiologists with 10-year experience. Sensitivity, specificity, and accuracy for both FFD- and DBT-galactography were calculated having histological examinations of surgical specimens as a reference standard. Data were presented as percentages with their 95% confidence intervals (CI). McNemar test was used. Interobserver agreement was assessed by using Cohen κ test for both techniques. RESULTS: Sensitivity was 41/43 (95%, 95% CI 84.2-99.4) for DBT-galactography and 33/43 (77%, 95% CI 61.4-88.2) for FFD-galactography (p = 0.008), specificity 6/6 (100%, 95% CI 54.1-100.0) for both imaging tools, accuracy 47/49 (96%, 95% CI 86.0-99.5) and 39/49 (80%, 95% CI 65.7-89.8) (p = 0.038), respectively. The inter-observer agreement was 0.86 for DBT-galactography and 0.78 for FFD-galactography. The AGD resulted to 1.94 ± 0.64 for the combined technique. CONCLUSION: DBT-galactography showed a significantly higher sensitivity and accuracy than FFD-galactography for the identification of the intraductal findings, improving the possibility of a reliable diagnosis in patients with pathologic nipple-discharge.